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Exploration of a stably expressed gene as a reference is critical for the accurate evaluation of miRNAs isolated from small extracellular vesicles (sEVs). In this study, we analyzed small RNA sequencing on plasma sEV miRNAs in the training dataset (n = 104) and found that miR-140-3p was the most stably expressed candidate reference for sEV miRNAs. We further demonstrated that miR-140-3p expressed most stably in the validation cohort (n = 46) when compared to two other reference miRNAs, miR-451a and miR-1228-3p, and the commonly-used miRNA reference U6. Finally, we compared the capability of miR-140-3p and U6 as the internal reference for sEV miRNA expression by evaluating key miRNAs expression in lung cancer patients and found that miR-140-3p was more suitable as a sEV miRNA reference gene. Taken together, our data indicated miR-140-3p as a stable internal reference miRNA of plasma sEVs to evaluate miRNA expression profiles in lung cancer patients.
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Vesículas Extracelulares , Neoplasias Pulmonares , MicroARNs , Humanos , MicroARNs/sangre , MicroARNs/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangre , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Femenino , Masculino , Estándares de Referencia , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genéticaRESUMEN
Polyethylene terephthalate has been widely used in the packaging industry. Degraded PET micro-nano plastics could pose public health concerns following release into various environments. This study focuses on PET degradation under ultraviolet radiation using the NIST SPHERE facility at the National Institute of Standards and Technology in saturated humidity (i.e., ≥ 95 % relative humidity) and dry conditions (i.e., ≤ 5 % relative humidity) with varying temperatures (30 °C, 40 °C, and 50 °C) for up 20 days. ATR-FTIR was used to characterize the chemical composition change of degraded PET as a function of UV exposure time. The results showed that the cleavage of the ester bond at peak 1713 cm-1 and the formation of the carboxylic acid at peak 1685 cm-1 are significantly influenced by UV radiation. Furthermore, the formation of carboxylic acid was considerably higher at saturated humidity and 50 °C conditions compared to dry conditions. The ester bond cleavage was also more pronounced in saturated humidity conditions. The novelty of this study is to provide insights into the chemical degradation of PET under environmental conditions, including UV radiation, humidity, and temperature. The results can be used to develop strategies to reduce the environmental impact of plastic pollution.
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Background: Acute superior mesenteric venous thrombosis (ASMVT) decreases junction-associated protein expression and intestinal epithelial cell numbers, leading to intestinal epithelial barrier disruption. Pyroptosis has also recently been found to be one of the important causes of mucosal barrier defects. However, the role and mechanism of pyroptosis in ASMVT are not fully understood. Methods: Differentially expressed microRNAs (miRNAs) in the intestinal tissues of ASMVT mice were detected by transcriptome sequencing (RNA-Seq). Gene expression levels were determined by RNA extraction and reverse transcription-quantitative PCR (RT-qPCR). Western blot and immunofluorescence staining analysis were used to analyze protein expression. H&E staining was used to observe the intestinal tissue structure. Cell Counting Kit-8 (CCK-8) and fluorescein isothiocyanate/propidine iodide (FITC/PI) were used to detect cell viability and apoptosis, respectively. Dual-luciferase reporter assays prove that miR-138-5p targets NLRP3. Results: miR-138-5p expression was downregulated in ASMVT-induced intestinal tissues. Inhibition of miR-138-5p promoted NLRP3-related pyroptosis and destroyed tight junctions between IEC-6 cells, ameliorating ASMVT injury. miR-138-5p targeted to downregulate NLRP3. Knockdown of NLRP3 reversed the inhibition of proliferation, apoptosis, and pyroptosis and the decrease in tight junction proteins caused by suppression of miR-138-5p; however, this effect was later inhibited by overexpressing HMGB1. miR-138-5p inhibited pyroptosis, promoted intestinal epithelial tight junctions and alleviated ASMVT injury-induced intestinal barrier disruption via the NLRP3/HMGB1 axis.
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Proteína HMGB1 , Isquemia Mesentérica , MicroARNs , Trombosis , Animales , Ratones , Enfermedad Aguda , Proteína HMGB1/genética , Venas Mesentéricas/metabolismo , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genéticaRESUMEN
Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral T-Cell Lymphomas (r/r PTCL), resulting in highly unsatisfactory treatment outcomes for these patients. This review provides an overview of potential mechanisms contributing to PTCL treatment resistance, encompassing aspects such as tumor heterogeneity, tumor microenvironment, and abnormal signaling pathways in PTCL development. The existing drugs aimed at overcoming PTCL resistance and their potential resistance mechanisms are also discussed. Furthermore, a summary of ongoing clinical trials related to PTCL is presented, with the aim of aiding clinicians in making informed treatment decisions.
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Neoplasias Hematológicas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Neoplasias Hematológicas/tratamiento farmacológico , Microambiente TumoralRESUMEN
Background: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. Methods: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated. Results: There were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN (P < 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients (P < 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858). Conclusion: Our findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Femenino , Nefritis Lúpica/diagnóstico , Inmunoglobulina G/metabolismo , Estudios de Casos y Controles , Glicosilación , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , PolisacáridosRESUMEN
ABSTRACT: Damage to the abdominal aortic wall and the local inflammatory response are key factors resulting in abdominal aortic aneurysm (AAA) formation. During this process, macrophage polarization plays a key role. However, in AAA, the regulatory mechanism of macrophages is still unclear, and further research is needed. In this study, we found that the transcription factor TCF3 was expressed at low levels in AAA. We overexpressed TCF3 and found that TCF3 could inhibit MMP and inflammatory factor expression and promote M2 macrophage polarization, thereby inhibiting the progression of AAA. Knocking down TCF3 could promote M1 polarization and MMP and inflammatory factor expression. In addition, we found that TCF3 increased miR-143-5p expression through transcriptional activation of miR-143-5p , which further inhibited expression of the downstream chemokine CCL20 and promoted M2 macrophage polarization. Our research indicates that TCF3-mediated macrophage polarization plays a key regulatory role in AAA, complementing the role and mechanism of macrophages in the occurrence and development of AAA and providing a scientific basis for AAA treatment.
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Aneurisma de la Aorta Abdominal , MicroARNs , Humanos , Factores de Transcripción/metabolismo , Quimiocina CCL20/genética , Quimiocina CCL20/metabolismo , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/metabolismo , Macrófagos/metabolismo , Inflamación/genética , Inflamación/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismoRESUMEN
Oncogenic super-enhancers (SEs) generate noncoding enhancer/SE RNAs (eRNAs/seRNAs) that exert a critical function in malignancy through powerful regulation of target gene expression. Herein, we show that a JUN-mediated seRNA can form R-loop to regulate target genes to promote metastasis of nasopharyngeal carcinoma (NPC). A combination of global run-on sequencing, chromatin-immunoprecipitation sequencing, and RNA sequencing was used to screen seRNAs. A specific seRNA associated with NPC metastasis (seRNA-NPCM) was identified as a transcriptional regulator for N-myc downstream-regulated gene 1 (NDRG1). JUN was found to regulate seRNA-NPCM through motif binding. seRNA-NPCM was elevated in NPC cancer tissues and highly metastatic cell lines, and promoted the metastasis of NPC cells in vitro and in vivo. Mechanistically, the 3' end of seRNA-NPCM hybridizes with the SE region to form an R-loop, and the middle segment of seRNA-NPCM binds to heterogeneous nuclear ribonucleoprotein R (hnRNPR) at the promoter of distal gene NDRG1 and neighboring gene tribbles pseudokinase 1 (TRIB1). These structures promote chromatin looping and long-distance chromatin interactions between SEs and promoters, thus facilitating NDRG1 and TRIB1 transcription. Furthermore, the clinical analyses showed that seRNA-NPCM and NDRG1 were independent prognostic factors for NPC patients. seRNA-NPCM plays a critical role in orchestrating target gene transcription to promote NPC metastasis.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , ARN , Estructuras R-Loop , Carcinoma/genética , Cromatina , Neoplasias Nasofaríngeas/genética , Proteínas Serina-Treonina Quinasas , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Prior research has indicated that animal models of abdominal aortic aneurysm (AAA) utilizing porcine pancreatic elastase (PPE) exhibit a perfusion duration of 30 min, and extended perfusion durations are associated with elevated mortality rates. Similarly, the AAA model, which relies solely on balloon dilation (BD), is limited by the occurrence of self-healing aneurysms. Consequently, we constructed a novel AAA model by PPE combined with balloon expansion to shorten the modeling time and improve the modeling success rate. The findings indicated that 5 min was the optimal BD time for rabbits, 3 min BD was ineffective for aneurysm formation, and 10 min BD had a high mortality rate. The model, constructed in combination with PPE and 5 min BD, exhibited a 100% model formation rate and a 244.7% ± 9.83% dilation rate. HE staining exhibited that severe disruption of the inner, middle, and outer membranes of the abdominal aorta, with a marked decrease in smooth muscle cells and elastase, and a marked increase in fibroblasts of the middle membrane, and many infiltrating inflammatory cells were seen in all three layers, especially in the middle membrane. EVG staining displayed that the elastic fibers of the abdominal aortic wall were fractured and degraded, and lost their normal wavy appearance. The protein expression of inflammatory factor (IL-1ß, IL-6 and TNF-α) as well as extracellular matrix components (MMP-2 and MMP-9) were significantly increased compared to PPE and 5 min BD alone. In conclusion, PPE combined with BD allows the establishment of a novel AAA model that closely mimics human AAA in terms of histomorphology, inflammatory cell infiltration, and vascular stromal destruction. This model provides an ideal animal model for understanding the pathogenesis of AAA.
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BACKGROUND: Soil-transmitted helminths (STHs) were previously endemic in Shandong Province, China. This study aimed to analyze the STHs prevalence trend and the natural, social, and human cognitive and behavioural factors influencing the discrepancies between high and low infection levels from 2016 to 2020 in Shandong Province in eastern China. METHODS: STHs surveillance data of Shandong Province from 2016 to 2020 were obtained from China Information Management System for Prevention and Control of Parasitic Diseases. STHs infections were detected by modified Kato-Katz method. Comprehensive information on the natural and social factors, STHs-related knowledge and behaviours were collected through questionnaire surveys. Retrospective spatial scan analysis was performed using SaTScan v10.1 to evaluate any identified spatial clusters of STHs infection for statistical significance and Bayes discriminant analysis was used to discriminate the high or low infection groups of the villages. RESULTS: In total, 72,160 participants were involved in our survey from 2016 to 2020. The overall STHs prevalence rate was 1.13%, with the eastern region of Shandong Province having the highest rate (2.02%). The predominant species was T. trichiura, with the prevalence rate of 0.99% and the ≥ 70-year age group possessed the highest rate of 2.21%. The STHs prevalence rate showed an annual linear downward trend from 2016 to 2020 ([Formula: see text] = 127.600, P < 0.001). Respondents aged ≥ 60 years had the lowest awareness level of STHs-related prevention knowledge (all P < 0.05), and were the most likely to adopt the practice of fertilizing with fresh stool (χ2 = 28.354, P < 0.001). Furthermore, the southern region demonstrated the highest temperature and rainfall level and the lowest GNP and annual net income per capita (all P < 0.05). CONCLUSIONS: There is a remarkable declining in STHs prevalence in Shandong Province from 2016 to 2020. However, the prevalence rates of STHs especially T. trichiura in the southern and eastern regions were still high, and the elderly were more susceptible to be infected with STHs owning to their low awareness level of STHS-related prevention knowledge and high adoption rate of dangerous production and living behaviours. Integrated approaches of health education, environment improvement and behaviour change should be strengthened to obtain a further reduction of STHs prevalence in China.
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Helmintiasis , Helmintos , Anciano , Animales , Humanos , Suelo/parasitología , Prevalencia , Teorema de Bayes , Estudios Retrospectivos , Helmintiasis/epidemiología , China/epidemiología , Heces/parasitologíaRESUMEN
Introduction: In China, alfalfa (Medicago sativa L.) is often grown on marginal land with poor soil fertility and suboptimal climate conditions. Soil salt stress is one of the most limiting factors for alfalfa yield and quality, through its inhibition of nitrogen (N) uptake and N fixation. Methods: To understand if N supply could improve alfalfa yield and quality through increasing N uptake in salt-affected soils, a hydroponic experiment and a soil experiment were conducted. Alfalfa growth and N fixation were evaluated in response to different salt levels and N supply levels. Results and discussion: The results showed that salt stress not only significantly decreased alfalfa biomass, by 43%-86%, and N content, by 58%-91%, but also reduced N fixation ability and N derived from the atmosphere (%Ndfa) through the inhibition of nodule formation and N fixation efficiency when the salt level was above 100 mmol Na2SO4 L-1. Salt stress also decreased alfalfa crude protein by 31%-37%. However, N supply significantly improved shoot dry weight by 40%-45%, root dry weight by 23%-29%, and shoot N content by 10%-28% for alfalfa grown in salt-affected soil. The N supply was also beneficial for the %Ndfa and N fixation for alfalfa with salt stress, and the increase reached 47% and 60%, respectively. Nitrogen supply offset the negative effects on alfalfa growth and N fixation caused by salt stress, in part through improving plant N nutrition status. Our results suggest that optimal N fertilizer application is essential to alleviate the loss of growth and N fixation in alfalfa in salt-affected soils.
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Background: Abdominal aortic aneurysm (AAA) manifest as a natural inflammatory process with permanent dilation and terminal rupture. Nevertheless, the pathogenesis of AAA remains a mystery, and treatment is still controversial. Lipid metabolism and immune system are involved in AAA progression, which has been well documented. However, lipid- and immune-related (LIR) biomarkers need to be further elucidated. Methods: The AAA-related datasets were retrieved from the GEO database, and the datasets were analyzed for differential gene expression by NetworkAnalyst. GO and KEGG pathway enrichment analysis of differentially expressed mRNA (DE-mRNA) was performed using Metscape, and LIR DE-mRNA was further screened. AAA rat model was constructed using porcine pancreatic elastase to verify the differential expression of LIR DE-mRNA. Results: The GSE47472 and GSE57691 datasets respectively identified 614 (containing 381 down-regulated and 233 up-regulated DE-mRNAs) and 384 (containing 218 down-regulated and 164 up-regulated DE-mRNAs) DE-mRNAs. Intersection and union of DE-mRNAs were 13 and 983, respectively. The main terms involved in the union of DE-mRNAs included "immune system process", "metabolic process", "Chemokine signaling pathway", "hematopoietic cell lineage" and "Cholesterol metabolism". In vivo experiments revealed that LIR DE-mRNAs of PDIA3, TYROBP, and HSPA1A were significantly low expression in AAA abdominal aortic tissues, and HCK and SERPINE1 were significantly high expression, which is consistent with the bioinformatics analysis. Conclusions: PDIA3, TYROBP, HSPA1A, HCK and SERPINE1 may serve as LIR biomarkers of AAA, which provides new insights and theoretical guidance for the future treatment, early prevention and progression of AAA.
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As a class of persistent organic pollutant, polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PBDEs and MeO-PBDEs) have been widely detected in soil environments. However, studies on the bioavailability and transformation of PBDEs and their derivatives in soil organisms remain scarce. In this study, a detailed kinetic investigation on the accumulation and biotransformations of BDE-47, 6-MeO-BDE-47 and 6-OH-BDE-47 in earthworms (Eisenia fetida) exposed to artificially contaminated soils was conducted. The uptake and elimination kinetics of BDE-47, 6-MeO-BDE-47 and 6-OH-BDE-47 by earthworms were in accordance with a one-compartment first-order kinetic model. The bioaccumulation factors (BAFs) followed the order 6-MeO-BDE-47 > 6-OH-BDE-47 > BDE-47. All three compounds could undergo step-by-step debromination to produce lower brominated analogs in earthworms. Both BDE-47 and 6-OH-BDE-47 could be transformed to MeO-PBDEs, whereas no transformation from 6-OH-BDE-47 or 6-MeO-BDE-47 to PBDEs or from BDE-47 and 6-MeO-BDE-47 to OH-PBDEs took place in the earthworms. Methoxylation was proposed as a potential metabolic pathway to form MeO-PBDEs in earthworms, with the metabolic rates for the methoxylation of BDE-47 and 6-OH-BDE-47 being 27.7 and 5.1 times greater, respectively, than that of the debromination metabolism. The isomers of 6-MeO-BDE-47 and 6-OH-BDE-47 were formed via the addition of methoxy/hydroxy groups or via bromine shifts on benzene ring in the earthworms. This study provides comprehensive information for a better understanding of the accumulation and biotransformation of PBDEs and their derivatives in earthworms.
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Éteres Difenilos Halogenados , Oligoquetos , Animales , Éteres Difenilos Halogenados/análisis , Oligoquetos/metabolismo , Éter , Hidroxilación , Biotransformación , Éteres de Etila , SueloRESUMEN
Introduction: In China, alfalfa (Medicago sativa L.) often grows in marginal land with poor soil fertility and suboptimal climate conditions. Alfalfa production cannot meet demands both in yield and quality. It is necessary to apply fertilizers to achieve high yields and produce high-quality alfalfa in China. However, there is no understanding on the impact of fertilizer application on alfalfa production and the possible optimal application rates across China. Methods: We conducted a meta-analysis to explore the contribution of fertilizer application to the yield and quality of alfalfa based on a dataset from 86 studies published between 2004 and 2022. Results and Discussion: The results showed that fertilizer application not only increased alfalfa yield by 19.2% but also improved alfalfa quality by increasing crude protein (CP) by 7.7% and decreasing acid detergent fibre by 2.9% and neutral detergent fibre by 1.8% overall compared to the non-fertilizer control levels. The combined nitrogen (N), phosphorus (P) and potassium (K) and combined NP fertilizer applications achieved the greatest yield and CP concentration increases of 27.0% and 13.5%, respectively. Considering both yield and quality, the optimal rate of fertilizer application ranged from 30 to 60 kg ha-1 for N, 120 to 150 kg ha-1 for P and less than 120 kg ha-1 for K. Meta-analysis further showed that the effect of fertilizer application on yield was greater in low soil organic matter (SOM) soils than in high SOM soils. In conclusion, fertilizer application is an effective strategy to improve the yield and quality of alfalfa in China, especially that grown in low SOM soils. This study is helpful for optimizing fertilization schedules of alfalfa in China.
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High-fructose corn syrup (HFCS) has been speculated to have stronger negative metabolic effects than sucrose. However, given the current equivocality in the field, the aim of the present study was to determine the impact of HFCS use compared to sucrose on anthropometric and metabolic parameters. We searched PubMed, Scopus, Cochrane Central and web of sciences, from database inception to May 2022. A random effects model and the generic inverse variance method were applied to assess the overall effect size. Heterogeneity analysis was performed using the Cochran Q test and the I2 index. Four articles, with 9 arms, containing 767 participants were included in this meta-analysis. Average HFCS and sucrose usage equated to 19% of daily caloric intake. Combined data from three studies indicated that HFCS intake does not significantly change the weight (weighted mean difference (WMD): -0.29 kg, 95% CI: -1.34, 0.77, I2 = 0%) when compared to the sucrose group. Concordant results were found for waist circumstance, body mass index, fat mass, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Moreover, overall results from three studies indicated a significant increase in CRP levels (WMD: 0.27 mg/l, 95% CI: 0.02, 0.52, I2 = 23%) in the HFCS group compared to sucrose. In conclusion, analysis of data from the literature suggests that HFCS consumption was associated with a higher level of CRP compared to sucrose, whilst no significant changes between the two sweeteners were evident in other anthropometric and metabolic parameters.
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Objective: To explore the mechanisms of TLR9 from macrophages on mitochondrial apoptosis in cardiomyocytes at early stage of sepsis. Methods: The in vivo and in vitro sepsis mice were bone marrow transplantation (BMT) with wild type (WT) or (toll-like receptor 9) TLR9 knockout (-/- or KO) myeloid cells and then constructed by cecum ligation and puncture (CLP) as vivo experiment and cardiomyocytes cocultured with WT or TLR9-deficient macrophages treated with LPS as vitro experiment, respectively. Sepsis model were performed by CLP. The expression levels of exosome, PI3K/AKT, and ERK1/2, inflammatory factors, and apoptotic proteins were tested by western blot in vivo. Besides, associated apoptotic proteins and JC-1 fluorescence assay were tested in vitro. Results: The expressions of p-PI3K, p-AKT, exosome markers (CD9, CD63, and TSG101), p-ERK1/2, TNF-α, IFN-γ, IL-1ß, and cleaved-caspase-3/-9 were significantly increased in septic mice vs. control mice, and these proteins were declined dramatically in TLR9-/- BMT mice vs. WT BMT mice in sepsis mice models. Meanwhile, the protein expression of cytochrome C, cleaved-caspase-3, and cleaved-caspase-9 increased significantly in primary mouse myocardial cells cocultured with TLR9-/- or WT macrophages stimulated with LPS, and these mitochondrial apoptotic proteins as well as the green 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolcarbocyanine iodide (JC-1) fluorescence were dramatically lower in LPS-stimulated cardiomyocytes cocultured with TLR9-/- than with WT macrophages. Conclusion: TLR9-/- in macrophages suppressed the inflammatory reaction as well as the exosome secretion and resulted in the inhibition of apoptosis and oxidative stress in sepsis-induced cardiomyopathy.
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Exosomas , Sepsis , Animales , Apoptosis , Bencimidazoles , Carbocianinas , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Citocromos c/metabolismo , Exosomas/metabolismo , Yoduros , Lipopolisacáridos/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sepsis/metabolismo , Receptor Toll-Like 9/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Objective: Young adults of age 18-29 years old account for the most COVID-19 cases in the US, and ethnic groups were affected disproportionately. Correctly wearing a face mask remains a critical intervention for COVID-19 mitigation. The study aimed to examine how well Historically Black Colleges and Universities (HBCUs) residents adhered to mask wearing during the pandemic. Methods: We conducted an observational study on an urban HBCU campus and the neighborhoods in Maryland for 13 weeks in spring 2021. Results: Of 1926 (1126 on campus; 800 off campus) persons observed, 89.8% wore masks, with 83.5% covering their mouths and noses. The HBCU campus showed better mask adherence than neighborhoods (92.0% vs. 86.7%). The most common improper mask wearing was nose out, followed by only-on-chin. Cloth and surgical masks were worn the most. Conclusion: The HBCU campus and neighborhood settings presented a high rate of facemask use during the pandemic.
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Objectives: Abdominal aortic aneurysm (AAA) has a high risk of rupture of the aorta and is one of the leading causes of death in older adults. This study is aimed at confirming the influence and mechanism of the abnormally expressed ANXA6 gene in AAA. Methods: Clinical samples were collected for proteome sequencing to screen for differentially expressed proteins. An Ang II-induced vascular smooth muscle cell (VSMC) aging model as well as an AAA animal model was used. Using RT-qPCR to detect the mRNA levels of EZH2, ANXA6, IK-6, and IL-8 in cells and tissues were assessed. Western blotting and immunohistochemistry staining were used apply for the expression of associated proteins in cells and tissues. SA-ß-gal staining, flow cytometry, and DHE staining were used to detect senescent cells and the level of ROS. The cell cycle was assessed by flow cytometry. Arterial pathology was observed by HE staining. The aging of VSMCs in arterial tissue was assessed by coimmunofluorescence for α-SMA and p53. Results: There were 24 differentially expressed proteins in the AAA clinical samples, including 10 upregulated protein and 14 downregulated protein, and the differential expression of ANXA6 was associated with vascular disease. Our study found that ANXA6 was highly expressed and EZH2 was lowly expressed in an Ang II-induced VSMC aging model. Knockdown of ANXA6 or overexpression of EZH2 inhibited Ang II-induced ROS, inhibited cell senescence, decreased Ang II evoked G1 arrest, and increased cells in G2 phase, while overexpression of ANXA6 played the opposite role. Overexpression of EZH2 inhibited ANXA6 expression by increasing H3K27me3 modification at the ANXA6 promoter. Simultaneous overexpression of EZH2 and the protective effect of EZH2 on cell senescence were partially reversed by ANXA6. Similarly, ANXA6 was highly expressed and EZH2 was lowly expressed in an Ang II-induced AAA animal model. Knockdown of ANXA6 and overexpression of EZH2 alleviated Ang II-induced VSMC senescence and inhibited AAA progression, while simultaneous overexpression of EZH2 and ANXA6 partially reversed the protective effect of EZH2 on AAA. Conclusion: EZH2 regulates the ANXA6 promoter H3K27me3 modification, inhibits ANXA6 expression, alleviates Ang II-induced VSMC senescence, and inhibits AAA progression.
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Angiotensina II , Músculo Liso Vascular , Angiotensina II/metabolismo , Angiotensina II/farmacología , Animales , Senescencia Celular , Modelos Animales de Enfermedad , Histonas/metabolismo , Interleucina-8/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Proteoma/metabolismo , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Objectives: Intestinal epithelial barrier function is an important mechanical barrier to maintain intestinal homeostasis and resist the invasion of intestinal pathogens and microorganisms. However, intestinal epithelial barrier function is vulnerable to damage under intestinal ischemia-reperfusion (I/R) injury. Under a category of pathophysiological conditions, including I/R, autophagy plays a crucial role. This study is aimed at discussing the role of autophagy inhibitors and activators in intestinal epithelial barrier function after intestinal I/R by changing autophagy levels. Methods: Mice with intestinal IR underwent 45 minutes of surgery for superior mesenteric artery occlusion. The autophagy inhibitor 3-MA and the autophagy inducer rapamycin (RAP) were used to change the level of autophagy, and then, the expressions of tight junction proteins and intestinal barrier function were detected. Results: The results showed that the autophagy inhibitor 3-MA aggravated intestinal epithelial barrier dysfunction, while the autophagy inducer RAP attenuated intestinal epithelial barrier dysfunction. In addition, promoting autophagy may promote occludin expression by inhibiting claudin-2 expression. Conclusion: Upregulation of autophagy levels by autophagy inducers can enhance intestinal epithelial barrier function after intestinal I/R.
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Autofagia , Daño por Reperfusión , Animales , Mucosa Intestinal/metabolismo , Isquemia , Ratones , Reperfusión , Daño por Reperfusión/metabolismo , Proteínas de Uniones Estrechas/metabolismoRESUMEN
We report a method to prepare core-shell zeolite beta (*BEA) with an aluminous core and an epitaxial Si-rich shell. This method capitalizes on the inherent defects in *BEA crystals to simultaneously passivate acid sites on external surfaces and increase intracrystalline mesoporosity through facile post-hydrothermal synthesis modification in alkaline media. This process creates more hydrophobic materials by reducing silanol defects and enriching the shell in silica via a combination of dealumination and the relocation of silica from the core to the shell during intracrystalline mesopore formation. The catalytic consequences of *BEA core-shells relative to conventional analogues were tested using the biomass conversion of levulinic acid and n-butanol to n-butyl levulinate as a benchmark reaction. Our findings reveal that siliceous shells and intracrystalline mesopores synergistically enhance the performance of *BEA catalysts.