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BACKGROUND: The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy. METHODS: We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis. RESULTS: We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p < 0.001). The results of multivariable logistic analysis showed that the risk of SAP increased with the SIRI value (OR = 1.169, 95% CI = 1.049-1.344, p = 0.014). Age ≥ 60 (OR = 4.076, 95% CI = 1.251-14.841, p = 0.024) was also statistically significant. A nomogram with SIRI showed good prediction accuracy for SAP in AIS patients treated by thrombectomy (C-index value = 0.774). CONCLUSIONS: SIRI is an independent predictor for SAP in patients with AIS treated by thrombectomy. A high SIRI value may allow for the early identification of patients with AIS treated by thrombectomy at high risk for SAP.
Subject(s)
Ischemic Stroke , Pneumonia , Thrombectomy , Humans , Male , Female , Ischemic Stroke/surgery , Ischemic Stroke/complications , Ischemic Stroke/diagnosis , Aged , Retrospective Studies , Thrombectomy/methods , Middle Aged , Pneumonia/diagnosis , Pneumonia/epidemiology , Predictive Value of Tests , Nomograms , Aged, 80 and over , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiologyABSTRACT
BACKGROUND: Previous research on the association between physical activity (PA) and kidney function is inconsistent. The association between muscle mass and serum creatinine (SCr) may have implications for interpreting the effect of PA on estimated glomerular filtration rate (eGFR). Few studies have reported changes in physical activity and changes in kidney function. METHODS: A cohort study was constructed using the UK Biobank. Changes in physical activity were self-reported as metabolic equivalent task (MET) minutes/week. eGFR was calculated using SCr and cystatin C (CysC). Cox and nonlinear regressions with restricted cubic splines were applied to explore the association between changes in physical activity and rapid decline of kidney function (RDKF, eGFR annual decrease ≥3 mL/min/1.73 m2), and the annual change of eGFR. An exploratory analysis of cardiorespiratory fitness as the exposure was conducted. RESULTS: Among 11 757 participants, the median follow-up time was 4.4 years. Participants whose PA decreased by 1000 MET minutes/week at the follow-up assessment had a 2% reduction in risk of developing RDKFSCr (HR = 0.98, 95% CI: 0.96, 1.00). In contrast, a 1000 MET minutes/week increase in PA was associated with a 4% reduction in risk of developing RDKFCysC (HR = 0.96, 95% CI: 0.93, 0.99). A PA increase of 1000 MET minutes/week was associated with eGFRCysC annual increase of 0.04 mL/min/1.73 m2 (95% CI: 0.03, 0.06) but no significant changes in eGFRSCr. CONCLUSIONS: In this general population study, there are differing associations between changes in PA and changes in kidney function depending on the kidney biomarker used. Increasing PA is modestly associated with improving annual eGFRCysC and reduced risk of RDKF.
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AIM: To evaluate the association of glycated haemoglobin (HbA1c) and serum glucose with intraocular pressure (IOP) in a large UK general population. MATERIALS AND METHODS: Participants were selected from the UK Biobank, excluding those with eye conditions that may affect IOP. IOP was measured using an ocular response analyser. Goldmann-correlated IOP (IOPg) and corneal-compensated IOP (IOPcc) were outcomes of interest, and ocular hypertension was defined as left-eye IOPg or IOPcc > 21 mmHg. HbA1c and random (non-fasting) serum glucose were the exposures of interest. Multivariate restricted cubic spline models, as well as linear regression, were applied to explore the associations of interest. RESULTS: Among 68 806 participants (46.5% male), the mean age was 56.7 years. The mean (standard deviation) for IOPg was 15.7 (3.6) mmHg and 15.9 (3.6) mmHg for IOPcc. Occular hypertension was prevalent in 8055 participants (11.7%) and 4178 participants (6.1%) had diabetes. Those with diabetes had higher IOP and a higher prevalence of ocular hypertension. After adjustment for demographic and clinical variables, HbA1c was positively associated with IOP in participants with diabetes, but not in those without diabetes. For every 10-mmol/mol increase in HbA1c, IOPg increased by 0.20 mmHg (95% confidence interval [CI] 0.12, 0.28) and IOPcc by 0.15 mmHg (95% CI 0.07, 0.23); the odds of ocular hypertension was increased by 6% (95% CI 1.00, 1.13) in participants with diabetes. A borderline positive association between serum glucose and IOP was found only in participants without diabetes. CONCLUSIONS: Impaired glycaemic control was associated with elevated IOP and a possible risk of ocular hypertension among participants with diabetes but of normal ocular health.
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Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats' body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats.
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Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.
Subject(s)
Choroidal Neovascularization , NF-kappa B , Signal Transduction , Choroidal Neovascularization/metabolism , Choroidal Neovascularization/pathology , Choroidal Neovascularization/genetics , Animals , Mice , Humans , NF-kappa B/metabolism , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Macrophages/metabolism , Macrophages/immunology , Choroid/metabolism , Choroid/pathology , Choroid/blood supply , Male , Wet Macular Degeneration/metabolism , Wet Macular Degeneration/genetics , Wet Macular Degeneration/pathology , Inflammation/metabolism , Cytokines/metabolismABSTRACT
OBJECTIVE: This study aimed to investigate the expression of serine protease inhibitor kazal type 1 (SPINK1) and its carcinogenic effect in oral tongue squamous cell carcinoma (OTSCC). DESIGN: Initially, bioinformatics analysis was conducted using data from The Cancer Genome Atlas and Gene Expression Omnibus to compare SPINK1 mRNA expression between malignant and adjacent tissues. Subsequently, the impact of differential expression on survival and other clinical variables was examined. Additionally, histology microarray analysis was performed to assess SPINK1 protein expression in 35 cases of malignant and adjacent tissues. Finally, alterations in SPINK1 expression were evaluated to determine its biological phenotypes in OTSCC, including proliferation, apoptosis, invasion, and metastasis. RESULTS: OTSCC tissues exhibit higher levels of SPINK1 compared to surrounding cancerous tissues. Notably, increased SPINK1 expression correlates with the pathological N stage and independently predicts overall survival among patients with OTSCC. CONCLUSION: Suppression of SPINK1 inhibited OTSCC cell proliferation, invasion, and motility while promoting apoptosis. These findings suggest that SPINK1 may serve as a prognostic biomarker as well as a potential therapeutic target for managing OTSCC.
Subject(s)
Apoptosis , Biomarkers, Tumor , Carcinoma, Squamous Cell , Cell Proliferation , Disease Progression , Neoplasm Invasiveness , Tongue Neoplasms , Trypsin Inhibitor, Kazal Pancreatic , Humans , Tongue Neoplasms/pathology , Tongue Neoplasms/genetics , Tongue Neoplasms/metabolism , Trypsin Inhibitor, Kazal Pancreatic/genetics , Prognosis , Male , Female , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Middle Aged , Apoptosis/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Cell Movement/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics , Cell Line, Tumor , Computational BiologyABSTRACT
BACKGROUND: Due to their excellent stability, low toxicity, flexible modification and adjustable functionality, carbon dots (CDs) have a promising application prospect in the field of chromatographic stationary phases. Hydrogels are new functional polymer materials with three-dimensional network structure that have excellent hydrophilicity, high porosity and unique mechanical properties, which are also good candidate materials for liquid chromatography. Nevertheless, a review of the literature reveals that CDs based nanocomposite hydrogels have not yet been reported as HPLC stationary phases. RESULTS: In this work, amphiphilic CDs with multiple functional groups and polyacrylic acid hydrogel were grafted to the surface of silica gel by an in-situ polymerization method, and a CDs/polyacrylic acid nanocomposite hydrogel stationary phase (CDs/hydrogel@SiO2) was prepared. CDs act as the macroscopic cross-linking agents to form a cross-linked network with polyacrylic acid chains through physical cross-linking by hydrogen bonding and chemical cross-linking by amidation and esterification reactions, which not only improve the swelling property of the hydrogel but also increase its stability. Additionally, the introduction of CDs with multifunctional groups modulates the hydrophilic-hydrophobic balance of the hydrogel that also imparts good hydrophobicity to the composite hydrogel. Through the study of retention mechanism and influencing factors, it is certificate that the CDs/hydrogel@SiO2 has mixed-mode chromatographic performance. Furthermore, the CDs/hydrogel@SiO2 column shows great potential for the determination of organic contaminants in environmental water samples. SIGNIFICANCE: This work confirms the potential application of CDs/hydrogel composite for the separation of various samples and provides the possibility of developing CDs based nanocomposite hydrogel in the field of liquid chromatography. Introducing CDs into hydrogel can open up a new way for nanocomposite hydrogels to be used in HPLC, which expands the advance of hydrogel and CDs in separation field.
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BACKGROUND: Primary caregivers of hemodialysis patients suffer from varying degrees of stress from their patients. Caring for hemodialysis patients can expose caregivers to many problems, leading to an increased burden of care and even impacting the quality of care. The purpose of our study was to examine whether family resilience could be a mediating variable moderating the relationship between patient coping styles and caregiver burden. METHODS: The study was a cross-sectional and descriptive-analytical study that interviewed 173 pairs of hemodialysis patients and their caregivers at a blood purification center in a public hospital in China. The Brief Coping Styles Scale (Chinese version) was used to assess individuals' coping styles for disease and treatment. From the caregiver's perspective, the Family Resilience Assessment Scale (Chinese version) was used to understand the resilience of families, and the Zarit Caregiver Burden Scale was used to capture the caregiver's subjective experience of burden. Statistical analyses were conducted using SPSS version 23 and Amos version 26 to analyze the relationships between variables to examine for correlation and construct mediated effects models. RESULTS: Coping styles showed a significant positive correlation with family resilience (r = 0.347, P < 0.01) and a negative correlation with caregiver burden (r = -0.379, P < 0.01). A significant negative correlation was found between family resilience and caregiver burden (r = -0.503, P < 0.01). In the mediation model, patient coping styles directly impacted caregiver burden significantly (95% CI [-0.372, -0.058]), and coping styles indirectly impacted caregiver burden by family resilience in a significant way (95% CI [-0.275, -0.098]). CONCLUSIONS: Patient coping styles directly affect caregiver burden. Family resilience is a mediating variable between patients' coping styles and the burden on caregivers.
Subject(s)
Caregiver Burden , Psychological Tests , Resilience, Psychological , Self Report , Humans , Cross-Sectional Studies , Family Health , Coping Skills , Renal DialysisABSTRACT
Acute lung injury (ALI) is characterized by pulmonary diffusion abnormalities that may progress to multiple-organ failure in severe cases. There are limited effective treatments for ALI, which makes the search for new therapeutic avenues critically important. Macrophages play a pivotal role in the pathogenesis of ALI. The degree of macrophage polarization is closely related to the severity and prognosis of ALI, and S100A9 promotes M1 polarization of macrophages. The present study assessed the effects of S100A9-gene deficiency on macrophage polarization and acute lung injury. Our cohort study showed that plasma S100A8/A9 levels had significant diagnostic value for pediatric pneumonia and primarily correlated with monocyte-macrophages and neutrophils. We established a lipopolysaccharide (LPS)-induced mouse model of acute lung injury and demonstrated that knockout of the S100A9 gene mitigated inflammation by suppressing the secretion of pro-inflammatory cytokines, reducing the number of inflammatory cells in the bronchoalveolar lavage fluid, and inhibiting cell apoptosis, which ameliorated acute lung injury in mice. The in vitro and in vivo mechanistic studies demonstrated that S100A9-gene deficiency inhibited macrophage M1 polarization and reduced the levels of pulmonary macrophage chemotactic factors and inflammatory cytokines by suppressing the TLR4/MyD88/NF-κB signaling pathway and reversing the expression of the NLRP3 pyroptosis pathway, which reduced cell death. In conclusion, S100A9-gene deficiency alleviated LPS-induced acute lung injury by inhibiting macrophage M1 polarization and pyroptosis via the TLR4/MyD88/NFκB pathway, which suggests a potential therapeutic strategy for the treatment of ALI.
Subject(s)
Acute Lung Injury , Lipopolysaccharides , Humans , Child , Mice , Animals , Lipopolysaccharides/adverse effects , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Pyroptosis , Cohort Studies , Signal Transduction , Acute Lung Injury/metabolism , Macrophages/metabolism , Cytokines/metabolism , Calgranulin B/genetics , Calgranulin B/metabolismABSTRACT
Rationale: The transition from acute inflammation to fibrosis following myocardial ischemiaâreperfusion (MIR) significantly affects prognosis. Macrophages play a pivotal role in inflammatory damage and repair after MIR. However, the heterogeneity and transformation mechanisms of macrophages during this transition are not well understood. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and mass cytometry to examine murine monocyte-derived macrophages after MIR to investigate macrophage subtypes and their roles in the MIR process. S100a9-/- mice were used to establish MIR model to clarify the mechanism of alleviating inflammation and fibrosis after MIR. Reinfusion of bone marrow-derived macrophages (BMDMs) after macrophage depletion (MD) in mice subjected to MIR were performed to further examine the role of S100a9hi macrophages in MIR. Results: We identified a unique subtype of S100a9hi macrophages that originate from monocytes and are involved in acute inflammation and fibrosis. These S100a9hi macrophages infiltrate the heart as early as 2 h post-reperfusion and activate the Myd88/NFκB/NLRP3 signaling pathway, amplifying inflammatory responses. As the tissue environment shifts from proinflammatory to reparative, S100a9 activates transforming growth factor-ß (Tgf-ß)/p-smad3 signaling. This activation not only induces the transformation of myocardial fibroblasts to myofibroblasts but also promotes fibrosis via the macrophage-to-myofibroblast transition (MMT). Targeting S100a9 with a specific inhibitor could effectively mitigate acute inflammatory damage and halt the progression of fibrosis, including MMT. Conclusion: S100a9hi macrophages are a promising therapeutic target for managing the transition from inflammation to fibrosis after MIR.
Subject(s)
Coronary Artery Disease , Myocardial Reperfusion Injury , Mice , Animals , Macrophages/metabolism , Myocardial Reperfusion Injury/pathology , Fibrosis , Inflammation/metabolism , Coronary Artery Disease/pathology , Ischemia/pathology , Reperfusion , Sequence Analysis, RNA , Mice, Inbred C57BLABSTRACT
BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment. METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles. RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA. CONCLUSION: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Prognosis , Esophageal Neoplasms/genetics , Esophageal Neoplasms/therapy , Immunotherapy , Up-RegulationABSTRACT
Selective fractionation of hemicelluloses is of great significance for realizing high-value application of hemicelluloses and comprehensive utilization of lignocellulosic biomass. Tetramethylammonium hydroxide (TMAH) solvent has been confirmed as a promising solvent to selectively fractionate hemicelluloses from holocellulose. Herein, TMAH solvent was adopted to pretreat poplar thermomechanical pulp (PTMP) for the selective fractionation of hemicelluloses and enhancement of enzymatic hydrolysis performance of residues. The maximal hemicelluloses yield (65.0 %) and excellent cellulose retention rate (93.3 %) were achieved after pretreatment by the 25 wt% TMAH solvent, while the delignification was only 33.9 %. The hemicelluloses fractions could be selectively fractionated with high molecular weights (109,800-118,500 g/mol), the contents of Klason lignin in them were low (3.2-5.9 %), and the dominating structure of them was 4-O-methylglucurono-ß-D-xylan. Compared to the H2SO4 and NaOH methods, the hemicelluloses fractionated by TMAH method exhibited higher yields, more complete structures and higher molecular weights. Furthermore, the crystalline structure of cellulose practically remained stable, and the highest yield of enzymatic hydrolysis glucose was 57.5 %, which was 3.3 times of that of PTMP. The fractionation effectiveness of TMAH solvent was not significantly reduced after repeatedly recycling. This work demonstrated TMAH solvent could selectively fractionate hemicelluloses from PTMP and efficiently promote sustainable poplar-based biorefinery.
Subject(s)
Lignin , Polysaccharides , Populus , Quaternary Ammonium Compounds , Molecular Weight , Lignin/chemistry , Cellulose/chemistry , Solvents , Hydrolysis , BiomassABSTRACT
Coordinating multiple artificial cellular compartments into a well-organized artificial multicellular system (AMS) is of great interest in bottom-up synthetic biology. However, developing a facile strategy for fabricating an AMS with a controlled arrangement remains a challenge. Herein, utilizing in situ DNA hybridization chain reaction on the membrane surface, we developed a DNA patch-based strategy to direct the interconnection of vesicles. By tuning the DNA patch that generates heterotrophic adhesion for the attachment of vesicles, we could produce an AMS with higher-order structures straightforwardly and effectively. Furthermore, a hybrid AMS comprising live cells and vesicles was fabricated, and we found the hybrid AMS with higher-order structures arouses efficient molecular transportation from vesicles to living cells. In brief, our work provides a versatile strategy for modulating the self-assembly of AMSs, which could expand our capability to engineer synthetic biological systems and benefit synthetic cell research in programmable manipulation of intercellular communications.
Subject(s)
Artificial Cells , Biological Phenomena , Membranes/chemistry , DNA/chemistry , Artificial Cells/chemistry , Synthetic BiologyABSTRACT
Cardiovascular disease (CVD) is the most common cause of death, environmental factors, such as arsenic, playing an important role in the progress of CVD. Vascular endothelial dysfunction (VED) is a crucial early feature for CVD, inorganic arsenic (iAs) can induce autophagy in various cells. However, the role of endothelial autophagy has rarely been studied in VED triggered by arsenic. Total of one hundred and twenty healthy male C57BL/6J mice weighing 18-22 g were randomly divided into an arsenic-exposure group and a control group for 3, 6, 9, and 12 weeks. The results showed that, independent of the exposure period, autophagy markers of p-ATG16L1 levels and Beclin 1 contents in the aortic arch endothelium increased significantly compared with those of the corresponding control group. And different exposure duration decreased NO contents in the serum significantly. Combined with the histological changes that endothelial injury aggravated gradually with the increasing exposure period, suggesting that under exposure to iAs over 9 weeks, VED was remarkably induced, and consistant high levels of endothelial autophagy may play an important role. Additionally, levels of p-AMPKα/AMPKα increased significantly and p-mTORC1/mTORC1 levels decreased remarkably in the aortic arch endothelium. Then, a NaAsO2-induced-VED in vitro model was used to explore the mechanism of arsenic-induced endothelial autophagy. Similarly, p-AMPKα/AMPKα level significantly increased, and p-mTORC1/mTORC1 level remarkably decreased induced by 30 µmol/L NaAsO2 in HUAECs. Further, an AMPK inhibitor (Compound C) pre-treatment prior to arsenic exposure reversed the increased autophagy level, and alleviated the endothelial dysfunction in HUVECs, as shown by the significant increase in the intracellular NO content and the cell vitality. Mechanistically, we revealed that AMPKα is active in autophagy of endothelial cells in arsenic-induced VED by regulating mTORC1/p70S6K/ULK1. The present study provide a new promising target for prevention and control arsenic-associated CVD.
Subject(s)
Arsenic , Cardiovascular Diseases , Mice , Animals , Male , Mechanistic Target of Rapamycin Complex 1 , AMP-Activated Protein Kinases , Endothelial Cells , Arsenic/toxicity , Ribosomal Protein S6 Kinases, 70-kDa , Mice, Inbred C57BL , AutophagyABSTRACT
As one of the most critical economic traits, the litter performance of sows is influenced by their parity. Some studies have indicated a connection between the gut microbiota and the litter performance of animals. In this study, we examined litter performance in 1363 records of different parities of Large White sows. We observed a marked decline in TNB (Total Number Born) and NBH (Number of Healthy Born) We observed a marked decline in TNB (Total Number Born) and NBH (Number of Healthy Born) among sows with parity 7 or higher. To gain a deeper understanding of the potential role of gut microbiota in this phenomenon, we conducted 16S rRNA amplicon sequencing of fecal DNA from 263 Large White sows at different parities and compared the changes in their gut microbiota with increasing parity. The results revealed that in comparison to sows with a parity from one to six, sows with a parity of seven or higher exhibited decreased alpha diversity in their gut microbiota. There was an increased proportion of pathogenic bacteria (such as Enterobacteriaceae, Streptococcus, and Escherichia-Shigella) and a reduced proportion of SCFA-producing families (such as Ruminococcaceae), indicating signs of inflammatory aging. The decline in sow function may be one of the primary reasons for the reduction in their litter performance.