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BACKGROUND: Osteoarthritis (OA) is a common chronic joint disease that significantly affects an individual's quality-of-life and frailty has become one of the common complications in OA patients as the disease progresses. The relationship between dietary patterns is not clear. METHODS: All participants are from the National Health and Nutrition Examination Survey (NHANES) and have been diagnosed with OA. The dietary inflammation index (DII) is calculated based on the dietary intake reported by the participants. Logistic regression analysis is used to investigate the relationship between DII and frailty. Restricted cubic splines are utilised to explore their nonlinear relationship. Mediation analysis is conducted to explore the role of inflammation in this relationship. RESULTS: A total of 2,530 OA patients were included in the study, with an average age of 64.46 (12.67) years. After adjusting for covariates, for each one standard deviation increase in DII, the risk of frailty increased by 15% (OR = 1.15, 95% CI = 1.03-1.28). Compared to patients with DII < -1, patients with DII > 1 had a significantly higher risk of frailty (OR = 1.50, 95% CI = 1.05-2.14). CONCLUSIONS: The findings of this study indicate a positive association between DII and the risk of frailty in OA patients. These results underscore the potential impact of dietary interventions in improving the quality-of-life for OA patients.
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Dieta , Fragilidad , Inflamación , Encuestas Nutricionales , Osteoartritis , Humanos , Masculino , Femenino , Fragilidad/etiología , Persona de Mediana Edad , Inflamación/etiología , AncianoRESUMEN
BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is very common in ICU patients. It is important to understand the status quo of knowledge, attitude and behavior of ICU nurses about ICU-AW. This survey aimed to investigate the knowledge, attitude and behavior of ICU nurses about ICU-AW, to provide useful implications for clinical care. METHODS: ICU nurses from two tertiary hospitals in China from October 10 to November 15, 2023 were included. The ICU-AW knowledge, attitude and behavior questionnaire of ICU nurses with 31 items were used for survey. SPSS24.0 statistical software was used for data analysis. RESULTS: A total of 364 ICU nurses were included for survey. The ICU-AW knowledge of ICU nurses was 21.96 ± 5.72 (< 50% of the total knowledge score), the ICU-AW attitude of ICU nurses was 30.24 ± 5.05(< 75% of the total attitude score), the ICU-AW behavior of ICU nurses was 26.77 ± 5.81(< 75% of the total behavior score), the total score was 79.21 ± 12.69(< 75% of the total score). Nurses' ICU-AW knowledge, attitude and behavior were all correlated (all P < 0.05). Multiple linear regression analyses indicated that age, years of ICU work experience, professional ranks and titles, had received the training about the ICU-AW were the influencing factors of knowledge, attitude and behavior of ICU nurses about ICU-AW (all P < 0.05). CONCLUSIONS: The knowledge, attitude and behavior of ICU nurses' ICU-AW needs to be improved, and there are many influencing factors. Hospital nursing administrators should strengthen the training of nurses' ICU-AW knowledge and improve the cognitive and practical ability of ICU nurses on ICU-AW, so as to reduce the occurrence of ICU-AW.
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INTRODUCTION: Large prospective trials have demonstrated that finerenone could reduce the risk of cardiovascular death and progression of renal failure among patients with chronic kidney disease associated heart failure and/or type 2 diabetes mellitus (T2DM). The aim of this study was to explore the molecular mechanism of finerenone in the treatment of cardiorenal diseases through network pharmacology. METHODS: The STITH, SwissTargetPrediction, PharmMapper, DrugBank, and ChEMBL databases were used to screen the targets of finerenone. The disease-related targets were retrieved from the DisGeNET, GeneCards, CTD, OMIM, and MalaCards databases. The protein-protein interaction (PPI) network was conducted with STRING database and Cytoscape software. The clusterProfiler R package was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The interactions of key targets and finerenone were analyzed by molecular docking in Autodock software. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. Histopathology of myocardial and renal tissues was observed by hematoxylin-eosin (HE) staining, and detection of protein expressions was conducted using Western blotting. RESULTS: A total of 111 potential cardiorenal targets of finerenone were identified. The main mechanisms of action may be associated with lipids and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and diabetic cardiomyopathy. The hub targets demonstrated by the PPI network were CASP3, ALB, MMP9, EGFR, ANXA5, IGF1, SRC, TNFRSF1A, IL2, and PPARG, and the docking results suggested that finerenone could bind to these targets with high affinities. HE staining revealed the cardiorenal protection of finerenone on diabetic mice. In addition, the protein expressions of CASP3 and EGFR were increased while ALB was decreased in myocardial and renal tissues in diabetic mice compared with control mice, which were reversed by finerenone. CONCLUSION: This study suggested that finerenone exerts cardiorenal benefits through multiple targets and pathways.
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Diabetes Mellitus Experimental , Simulación del Acoplamiento Molecular , Naftiridinas , Farmacología en Red , Naftiridinas/farmacología , Animales , Ratones , Diabetes Mellitus Experimental/complicaciones , Mapas de Interacción de Proteínas , Masculino , Receptores ErbB/metabolismo , Receptores ErbB/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Ratones Endogámicos C57BL , Antagonistas de Receptores de Mineralocorticoides/farmacología , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
Biomolecular condensates are dynamic subcellular compartments that lack surrounding membranes and can spatiotemporally organize the cellular biochemistry of eukaryotic cells. However, such dynamic organization has not been realized in prokaryotes that naturally lack organelles, and strategies are urgently needed for dynamic biomolecular compartmentalization. Here we develop a light-switchable condensate system for on-demand dynamic organization of functional cargoes in the model prokaryotic Escherichia coli cells. The condensate system consists of two modularly designed and genetically encoded fusions that contain a condensation-enabling scaffold and a functional cargo fused to the blue light-responsive heterodimerization pair, iLID and SspB, respectively. By appropriately controlling the biogenesis of the protein fusions, the condensate system allows rapid recruitment and release of cargo proteins within seconds in response to light, and this process is also reversible and repeatable. Finally, the system is demonstrated to dynamically control the subcellular localization of a cell division inhibitor, SulA, which enables the reversible regulation of cell morphologies. Therefore, this study provides a new strategy to dynamically control cellular processes by harnessing light-controlled condensates in prokaryotic cells.
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The travel and tourism industry is among most severely impacted by natural disasters, terrorism, financial crises, and pandemics. Scholars are currently paying attention to how to revive tourism and establish tourist loyalty in the post-pandemic era. Aesthetics is a fundamental component of the tourist experience, and significantly affects tourist loyalty, intention, and behavior. However, research on destination aesthetics is limited, with most studies neglecting the role of memorability in the outcomes of aesthetics, particularly after the pandemic. Therefore, this study explores the mediating role of memorability in the effects of the aesthetic experiential qualities (scenery, cleanliness, harmony, art/architecture, and genuineness) of a nature-based tourism destination on tourist loyalty. Based on a two-wave panel data approach, 509 survey responses were collected and analyzed using Smarts. The findings indicate that the aesthetic experiential qualities positively affect tourists' memorability. Although three of the five aesthetic qualities (scenery, harmony, art/architecture) demonstrated no direct impact on loyalty, all the qualities had significant indirect effects on loyalty through the mediation of memorability. This study provides insights and new perspectives for promoting tourist loyalty in the context of post-pandemic tourism recovery.
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The buried interface of the perovskite layer has a profound influence on its film morphology, defect formation, and aging resistance from the outset, therefore, significantly affects the film quality and device performance of derived perovskite solar cells. Especially for FAPbI3 , although it has excellent optoelectronic properties, the spontaneous transition from the black perovskite phase to nonperovskite phase tends to start from the buried interface at the early stage of film formation then further propagate to degrade the whole perovskite. In this work, by introducing âNH3 + rich proline hydrochloride (PF) with a conjugated rigid structure as a versatile medium for buried interface, it not only provides a solid α-phase FAPbI3 template, but also prevents the phase transition induced degradation. PF also acts as an effective interfacial stress reliever to enhance both efficiency and stability of flexible solar cells. Consequently, a champion efficiency of 24.61% (certified 23.51%) can be achieved, which is the highest efficiency among all reported values for flexible perovskite solar cells. Besides, devices demonstrate excellent shelf-life/light soaking stability (advanced level of ISOS stability protocols) and mechanical stability.
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There is a wide variety of cancer cells that can be linked to the presence of TPX2. However, there is not a lot of evidence regarding its role in the development and maintenance of clear cell renal cell carcinoma (ccRCC). In our study, bioinformatics analysis was performed to obtain differentially expressed mRNAs and miR-NAs in ccRCC. Survival curves predicted correlation of TPX2 expression with patient survival. The upstream regulatory miRNA of TPX2 was predicted to be miRNA-27b-3p through database, and dual luciferase assay verified the targeted relationship. qRT-PCR and Western blot were employed for examination of TPX2 mRNA and protein expression in ccRCC cells. Proliferation, invasion, migration and cell cycle were detected by CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. The results showed that TPX2 showed very high expression in ccRCC, and patients with higher TPX2 expression had shorter relative survival. Low miRNA-27b-3p expression was found in ccRCC. Knockdown of TPX2 or forced expression of miRNA-27b-3p in ccRCC cells inhibited cell proliferation, migration, invasion, and arrested cell division in G0/G1 phase. Dual luciferase reporter presented that miRNA-27b-3p targeted TPX2 to inhibit its expression. Rescue experiments demonstrated that the miRNA-27b-3p/ TPX2 axis affected the biological functions of ccRCC cells. Concurrent overexpression of miRNA-27b-3p and TPX2 inhibited the facilitating effect of TPX2 on ccRCC cell growth. The results revealed novel regulatory mechanisms involved in ccRCC progression, hoping that it may spark an insight for later discovery about the new therapeutic targets for ccRCC.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , MicroARNs , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Renales/genética , Neoplasias Renales/patología , Luciferasas , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Asociadas a Microtúbulos/genéticaRESUMEN
Solid polymer electrolytes (SPEs) encounter the challenge of balancing high ionic conductivity and mechanical strength. Ionic liquids, which are among the contenders to be used in high-performance supercapacitors, have difficulty infiltrating commercial polyolefin separators for combined applications. In this study, a novel SPE involving uniform infiltration in the micropores of commercial polyolefin separators with polyethylene oxide (PEO), lithium salt, and different proportions of added ionic liquid was developed. The composite membranes combining ionic liquid-filled SPE with polypropylene (PP) microporous separators simultaneously achieve excellent mechanical strength and high-ionic conductivity. The low wettability of pure ionic liquids and commercial polyolefin-based separators is addressed. The 70 wt% IL-filled solid electrolyte composite membrane (PLI(70)@PP) exhibits a high ionic conductivity (2.9 × 10-3 S cm-1), low resistance at the electrolyte-electrode interface and excellent mechanical strength (128 MPa) at 25 °C. The all-solid-state supercapacitor using PLI(70)@PP exhibits a specific capacitance of 158 F g-1 at 0.1 A g-1 and stable cycle performance. The proposed method can be performed via high-volume roll-to-roll processing to obtain high-performance all-solid-state supercapacitors (ASSCs) for engineering applications.
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Skeletal muscle disuse atrophy can cause degenerative changes in neuromuscular junction morphology. Although Daurian ground squirrels (Spermophilus dauricus) are a natural anti-disuse animal model for studying muscle atrophy during hibernation, little is known about the morphological and regulatory mechanisms of their neuromuscular junctions. Here, we found that morphological indices of the soleus muscle were significantly lower during hibernation (torpor and interbout arousal) compared with pre-hibernation but recovered during post-hibernation. In the extensor digitorum longus muscle, neuromuscular junction morphology did not change significantly during hibernation. Agrin-Lrp4-MuSK is a key pathway for the formation and maintenance of the neuromuscular junction. Our results showed that low-density lipoprotein receptor-associated protein 4 (Lrp4) expression in the soleus (slow muscle) decreased by 46.2% in the interbout arousal group compared with the pre-hibernation group (P = 0.019), with recovery in the post-hibernation group. Compared with the pre-hibernation group, agrin expression in the extensor digitorum longus (fast muscle) increased by 67.0% in the interbout arousal group (P = 0.016). In conclusion, periodic up-regulation in agrin expression during interbout arousal may be involved in the maintenance of neuromuscular junction morphology in the extensor digitorum longus muscle during hibernation. The degenerative changes in neuromuscular junction morphology and the periodic decrease in Lrp4 protein expression in the soleus during hibernation, these changes recovered to the pre-hibernation levels in the post-hibernation group, exhibiting significant plasticity. This plasticity may be one of the important mechanisms for resisting disuse atrophy in hibernating animals.NEW & NOTEWORTHY This study is the first to explore the neuromuscular junction morphology of slow- and fast-twitch muscles in Daurian ground squirrels during different periods of hibernation. Results showed that the neuromuscular junction maintained stable morphology in the extensor digitorum longus muscle. The degenerative changes in neuromuscular junction morphology and the periodic decrease in Lrp4 protein expression in the soleus muscle during hibernation recovered in post-hibernation, exhibiting significant plasticity.
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Hibernación , Trastornos Musculares Atróficos , Animales , Sciuridae/metabolismo , Agrina/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Unión Neuromuscular , Factores de Transcripción/metabolismo , Trastornos Musculares Atróficos/patología , Hibernación/fisiologíaRESUMEN
The Stokes shift is negligible in bulk perovskites but large in two-dimensional (2D) CsPbBr3 perovskites. The issue has attracted a lot of discussion, but it remains controversial. Here, we report the temperature-dependent absorption and photoluminescence (PL) spectra of CsPbBr3 perovskite nanoplatelets (NPLs). We observe a temperature-dependent Stokes shift changing from 26 to 41 meV. This phenomenon was attributed to the exciton fine structure according to the great difference in peak width. The triple bright exciton levels all participate in the absorption process and result in a wide absorption peak, while only the lowest exciton level contributes to photon emission and exhibits a relatively narrow PL peak. The PL decay curves also present the characterization of bright and dark exciton couplings at low temperatures. The splitting of triple bright excitons is induced by the morphology anisotropy of the 2D structure, so the large Stokes shift is proposed to be an intrinsic property of 2D perovskites.
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INTRODUCTION: The role of submucosal injection during cold snare polypectomy (CSP) remains uncertain. In this study, we investigated the impact of submucosal saline injection during CSP for colorectal polyps sized 3-9 mm. METHODS: This was a multicenter randomized controlled trial conducted in 6 Chinese centers between July and September 2020 (ChiCTR2000034423). Patients with nonpedunculated colorectal polyps sized 3-9 mm were randomized in a 1:1 ratio to either CSP with submucosal injection (SI-CSP) or conventional CSP (C-CSP). The primary outcome was the incomplete resection rate (IRR). Secondary outcomes included procedure time, intraprocedural bleeding, delayed bleeding, and perforation. RESULTS: One hundred fifty patients with 234 polyps in the SI-CSP group and 150 patients with 216 polyps in the C-CSP group were included in the analysis. The IRR was not decreased in the SI-CSP group compared with that in the C-CSP group (1.7% vs 1.4%, P = 1.000). The median procedure time in the SI-CSP group was significantly longer than that in the C-CSP group (108 seconds vs 48 seconds, P < 0.001). The incidences of intraprocedural bleeding and delayed bleeding were not significantly different between the 2 groups ( P = 0.531 and P = 0.250, respectively). There was no perforation in either group. DISCUSSION: Submucosal saline injection during CSP for colorectal polyps sized 3-9 mm did not decrease the IRR or reduce adverse events but prolonged the procedure time.
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Pólipos del Colon , Neoplasias Colorrectales , Humanos , Pólipos del Colon/complicaciones , Colonoscopía/métodos , Microcirugia/efectos adversos , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/etiología , Neoplasias Colorrectales/etiologíaRESUMEN
Many tools are used to predict difficult airway, including bedside screening tests, radiological variables, and ultrasonography. However, the "gold standard" to identify difficult airway before intubation has not been established. The assessment and prediction of difficult airway is receiving increasing attention in clinical practice due to the devastating results of failed oxygenation or intubation. A literature visualization study is necessary to understand the research trend and help tailor future research directions. Science citation index-expanded web of Science database were used to search for literature related to assessment and prediction of difficult airways published before May 9th, 2022. VOS viewer software was used for visual analysis, including literature statistics, and co-occurrence analysis. A total of 2609 articles were included. The amount of relevant research interest and literature is increasing every year. According to co-occurrence network analysis, the research results can be grouped into the following 5 clusters, intubation approaches, intubation in special populations, difficult airway assessment tests, intubation in critical care/emergency settings and education, and laryngoscopes. Co-occurrence overlay analysis showed that video laryngoscopes and index prediction (including computed tomography and ultrasonography), emerged recently and comprised an important percentage of current studies. It can be predicted that future studies should focus on understanding the upper airway anatomy and constructing risk index predictions. Based on current global research trends, risk index predictions are the next hot topics in the evaluation and prediction of difficult airways, and video laryngoscopes will continue to be a hot topic in this field.
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Laringoscopios , Laringe , Humanos , Intubación Intratraqueal/métodos , Tráquea , Bibliometría , Laringoscopía/métodosRESUMEN
Immunogenic cell death (ICD) is one of the mechanisms regulating cell death, which activates adaptive immunity in immunocompetent hosts and is associated with tumor progression, prognosis and therapeutic response. Endometrial cancer (EC) is one of the most common malignancies of the female genital tract, and the potential role of immunogenic cell death-related genes (IRGs) in the tumor microenvironment (TME) remains unclear. We describe the variation of IRGs and assess the expression patterns in EC samples from The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Based on the expression of 34 IRGs, we identified two different ICD-related clusters and subsequently differentially expressed genes between the two ICD-related clusters were used for the identification of two ICD gene clusters. We identified the clusters and found that alterations in the multilayer IRG were associated with patient prognosis and TME cell infiltration characteristics. On this basis, ICD score risk scores were calculated, and ICD signatures were constructed and validated for their predictive power in EC patients. To help clinicians better apply the ICD signature, an accurate nomogram was constructed. The low ICD risk group was characterized by high microsatellite instability, high tumor mutational load, high IPS score and stronger immune activation. Our comprehensive analysis of IRGs in EC patients suggested a potential role in the tumor immune interstitial microenvironment, clinicopathological features and prognosis. These findings may improve our understanding of the role of ICDs, and provide a new basis for assessing prognosis and developing more effective immunotherapeutic strategies in EC.
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Neoplasias Endometriales , Muerte Celular Inmunogénica , Humanos , Femenino , Microambiente Tumoral/genética , Neoplasias Endometriales/genética , Familia de Multigenes , MutaciónRESUMEN
Antimicrobial resistance (AMR) has become a major global health concern prompting the quest for new antibiotics with higher efficiency and less proneness to drug resistance. Antimicrobial peptides (AMPs) offer such properties and have therefore gained increasing attention as a new generation of antibiotics to overcome AMR. In an attempt to develop new highly selective and highly efficient antifungal peptides, a sequence (named At1) originating from the natural AMP Ponericin-W1 was used as a lead sequence for rational design of a series of short cationic antifungal peptides named At2-At12. The charge, hydrophobicity, and terminal amino acids of the peptides were modified in a systematic way to investigate the effect of such structural changes on the biological activity of the peptides. Among all the designed peptides, three peptides (coded as At3, At5 and At10) exhibited high antifungal activity without any significant hemolytic activity in human red blood cells. The higher selectivity of these peptides for fungal cells over human cells was further confirmed in cocultures of Candida albicans and human foreskin fibroblasts. These three peptides lacked any hydrophilic residues in their hydrophobic domain, contained lysine residues in their hydrophilic region and had an overall charge of 7+. They also had a higher helical content in microbial membrane mimicking DPPG SUVs than the rest of the peptides. The fungi did not develop any resistance to the designed antifungal peptides even after 25 generations indicating low AMR. At5 was also used in vivo for the treatment of wounds infected with Candida albicans in mice and showed superiority over fluconazole for treating infection and accelerating wound healing. There was an interplay between the hydrophobicity and positive charge density to determine the antifungal activity of the peptides. The results from this study suggest this class of antifungal peptides as promising candidates for antifungal drugs with high efficiency, high biocompatibility and low propensity for drug resistance.
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Antifúngicos , Péptidos Antimicrobianos , Humanos , Ratones , Animales , Péptidos Catiónicos Antimicrobianos/química , Candida albicans , Antibacterianos/químicaRESUMEN
Aiming at the traditional ecological footprint model, the improved ecological footprint of the carbon footprint effectively makes up for the singularity of the ecological footprint's consideration of carbon emissions, and plays an important role in promoting high-quality development and ecological sustainability. This paper selects 2015, 2018 and 2020 as important time points for the study, corrects the ecological footprint parameter factors based on net primary productivity (NPP), measures the ecological footprint after the improvement of the carbon footprint, studies the spatial and temporal variation in the ecological footprint at the 100-m grid scale with the support of IPCC greenhouse gas inventory analysis, and analyzes the current ecological conservation status of the Yellow River Delta. Additionally, in the context of a low carbon economy, the decoupling index of carbon emissions and GDP is extended to the evaluation and analysis of high-quality development. The study showed that (1) the ecological footprint of the Yellow River Delta has increased year by year, from 0.721 hm2·person- 1 to 0.758 hm2·person- 1, an average annual increase of 2.9%; the ecological carrying capacity has decreased from 0.40 hm2·person- 1 to 0.31 hm2·person- 1, an overall decrease of 28.59%. (2) The overall ecological deficit of the Yellow River Delta grid is lightly overloaded, with most of the ecological surplus occurring in the northern and eastern parts of the study area and a few moderate and heavy overloads in the center of the core area where there is a lot of built-up land and the area is small and easy to gather. (3) Based on the low-carbon economy analysis, 2015, 2017 and 2020 reach absolute decoupling and are in the ideal scenario. However, in the rest of the years, carbon emissions and economic development are still in a large contradiction, and decoupling has fluctuated and varied greatly in the last six years. The effective combination of ecological footprint and low carbon economy analysis provides an important theoretical basis for improving ecological conservation and achieving high-quality development.
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RATIONALE AND OBJECTIVE: Post-traumatic stress disorder (PTSD) is a prevalent and debilitating psychiatric disorder. However, its specific etiological mechanism remains unclear. Previous studies have shown that traumatic stress changes metabotropic glutamate receptor 5 (mGluR5) expression in the hippocampus (HIP) and prefrontal cortex (PFC). More importantly, mGluR5 expression is often accompanied by alterations in brain-derived neurotrophic factor (BDNF). Furthermore, BDNF/tropomyosin-associated kinase B (TrkB) signaling plays multiple roles, including roles in neuroplasticity and antidepressant activity, by regulating glutamate transporter-1 (GLT-1) expression. This study aims to explore the effects of inhibiting mGluR5 on PTSD-like behaviors and BDNF, TrkB, and GLT-1 expression in the HIP and PFC of inevitable foot shock (IFS)-treated rats. METHODS: Seven-day IFS was used to establish a PTSD rat model, and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) (10 mg/kg, intraperitoneal injection) was used to inhibit the activity of mGluR5 during IFS in rats. After modeling, behavioral changes and mGluR5, BDNF, TrkB, and GLT-1 expression in the PFC and HIP were examined. RESULTS: First, the IFS procedure induced PTSD-like behavior. Second, IFS increased the expression of mGluR5 and decreased BDNF, TrkB, and GLT-1 expression in the PFC and HIP. Third, the mGluR5 antagonist blocked the above behavioral and molecular alterations. CONCLUSIONS: mGluR5 was involved in IFS-induced PTSD-like behavior by changing BDNF, TrkB, and GLT-1 expression.
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Factor Neurotrófico Derivado del Encéfalo , Transportador 2 de Aminoácidos Excitadores , Receptor del Glutamato Metabotropico 5 , Receptor trkB , Trastornos por Estrés Postraumático , Animales , Ratas , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Corteza Prefrontal/metabolismo , Receptor del Glutamato Metabotropico 5/genética , Receptor del Glutamato Metabotropico 5/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo , Trastornos por Estrés Postraumático/genética , Trastornos por Estrés Postraumático/metabolismo , Transportador 2 de Aminoácidos Excitadores/genética , Transportador 2 de Aminoácidos Excitadores/metabolismoRESUMEN
BACKGROUND: Chronic unpredictable mild stress (CUMS) can induce depressive behaviours and alter the composition of the gut microbiome. Although modulating gut microbiota can improve depression-like behaviour in rats, the mechanism of action is unclear. Additionally, gut microbiota can affect brain function through the neuroendocrine pathway. This pathway may function by regulating the secretion of neurotransmitters such as tryptophan (TRP). Metabolites of TRP, such as 5-hydroxytryptamine (5-HT) and kynurenine (KYN), are related to the pathophysiological process of depression. Indoleamine-2, 3-dioxygenase-1 (IDO1) and Tryptophan hydroxylase 2 (TPH2) are the key rate-limiting enzymes in TRP metabolism and play an important role in KYN and 5-HT metabolism. METHODS: Rats were subjected to four weeks of CUMS and given rifaximin150 mg/kg by oral gavage daily. After modelling, we investigated the rat's behaviours, composition of the faecal microbiome, neurotransmitter metabolism and key metabolic enzymes of the TRP pathway in the hippocampus (HIP). RESULTS: Rifaximin administration improved depressive behaviour in rats, corrected intestinal microbiota disorders and HIP TRP metabolism and regulated the expression of IDO1 and TPH2 in the HIP. CONCLUSIONS: Rifaximin improves depression-like behaviour in CUMS rats by influencing the gut microbiota and tryptophan metabolism.
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Microbioma Gastrointestinal , Triptófano , Ratas , Animales , Triptófano/metabolismo , Depresión , Rifaximina/uso terapéutico , Serotonina/metabolismo , Quinurenina/metabolismo , Hipocampo/metabolismo , Estrés PsicológicoRESUMEN
Oxidative stress is a phenomenon caused by an imbalance between the production and accumulation of reactive oxygen species in cells and tissues that eventually leads to the production of various diseases. Here, we investigated the antioxidant effects of the extract from Sonchus brachyotus DC. (SBE) based on the 0.2% oxazolone-induced intestinal oxidative stress model of zebrafish. Compared to the model group, the treatment group alleviated oxazolone-induced intestinal tissue damage and reduced the contents of malondialdehyde, reactive oxygen species, IL-1ß, and TNF-α and then increased the contents of superoxide dismutase, glutathione peroxidase, and IL-10. The 16s rDNA gene sequencing findings demonstrated that SBE could increase the relative abundance of Fusobacteriota, Actinobacteriota, and Firmicutes and decrease the relative abundance of Proteobacteria. Based on the correlation analysis between the oxidative stress biomarkers and intestinal flora, we found that the trends of oxidative stress biomarkers were significantly correlated with intestinal microorganisms, especially at the genus level. The correlations of MDA, IL-1ß, and TNF-α were significantly negative with Shewanella, while SOD, GSH-Px, and IL-10 were significantly positive with Cetobacterium, Gemmobacter, and Flavobacterium. Consequently, we concluded that the antioxidant effect of SBE was realized through the interaction between oxidative stress biomarkers and gut microbiota.