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Background: Parkinson's disease (PD) is a neurodegenerative movement disorder that impacts various systems, including the substantia nigra (SN) par compacta (SNpc) and extranigral regions like the spinal cord. The presence of persistent inflammation in the SN and spinal cord is associated with movement difficulties in PD. Atractylenolide-I (ATR-I) is a natural sesquiterpene recognized for its anti-inflammatory and neuroprotective effects. This research aimed to assess the impact of ATR-I treatment on motor function and inflammation in MPTP-induced subacute PD mice, particularly focusing on the role of ATR-I in spinal cord inflammation. Methods: The motor functions of the mice were assessed using suspension and gait tests. Dopaminergic neuronal loss in the SNpc and microglial activation in both the SNpc and spinal cord were evaluated through immunofluorescence staining. The levels of inflammatory mediators in the spinal cord were measured using RT-qPCR analysis. The expressions of SIRT1 and PGC-1α in the spinal cord were analyzed through Western blotting and RT-qPCR. Results: ATR-I treatment improved motor deficits in MPTP-induced mice. Moreover, ATR-I reduced the loss of dopamine neurons and microglial activation in the SNpc of MPTP-induced mice. Additionally, ATR-I suppressed spinal cord inflammation by decreasing microglial activation and the mRNA expression of TNF-α, IL-1ß, and iNOS in MPTP-induced mice. Interestingly, ATR-I also upregulated SIRT1 and PGC-1α levels in the spinal cord of MPTP-induced mice. Conclusion: These findings suggest that ATR-I exhibits anti-inflammatory and neuroprotective properties in PD. The attenuation of spinal cord inflammation via the SIRT1/PGC-1α pathway may contribute to enhancing motor function, highlighting ATR-I as a potential therapeutic avenue for PD.
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Alzheimer's disease (AD) is one of the most common forms of neurodegenerative dementia. The etiology of AD is multifactorial, and its complex pathophysiology involves tau and amyloid-ß deposition, increased oxidative stress, neuroinflammation, metabolic disorders, and massive neuronal loss. Due to its complex pathology, no effective cure for AD has been found to date. Therefore, there is an unmet clinical need for the development of new drugs against AD. Natural products are known to be good sources of compounds with pharmacological activity and have potential for the development of new therapeutic agents. Naringin, a naturally occurring flavanone glycoside, is predominantly found in citrus fruits and Chinese medicinal herbs. Mounting evidence shows that naringin and its aglycone, naringenin, have direct neuroprotective effects on AD, such as anti-amyloidogenic, antioxidant, anti-acetylcholinesterase, and anti-neuroinflammatory effects, as well as metal chelation. Furthermore, they are known to improve disordered glucose/lipid metabolism, which is a high risk factor for AD. In this review, we summarize the latest data on the impact of naringin and naringenin on the molecular mechanisms involved in AD pathophysiology. Additionally, we provide an overview of the current clinical applications of naringin and naringenin. The novel delivery systems for naringin and naringenin, which can address their widespread pharmacokinetic limitations, are also discussed. The literature indicates that naringin and naringenin could be multilevel, multitargeted, and multifaceted for preventing and treating AD.
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Enfermedad de Alzheimer , Flavanonas , Fármacos Neuroprotectores , Flavanonas/farmacología , Flavanonas/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Péptidos beta-Amiloides/metabolismoRESUMEN
BACKGROUND: Increasing evidence has shown that environmental factors play a crucial role in the pathogenesis of periodontitis. Humans are simultaneously exposed to a variety of environmental brominated flame retardants (BFRs). However, the relationship between BFRs in periodontitis remains unclear. This study aimed to investigate the overall association between BFRs and periodontitis in a nationally representative US population and to further identify important chemicals. METHODS: Data from 3322 NHANES participants from 2009 to 2016 were used. Serum BFRs were registered, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE100, PBDE-153, PBDE-154, PBDE-183, PBDE-209 and PBB-153. Survey weighted generalized logistic regression models, restricted cubic splines (RCS) were conducted to assess single BFRs exposure with periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of BFRs mixtures with periodontitis and to identify significant chemicals. RESULTS: A total of 3322 participants were included in the study, of whom 1795 had periodontitis. After adjusting for potential confounders, multiple logistic regression analysis revealed significant positive associations between serum levels of PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153 and the risk of periodontitis (all P < 0.05). A dose-response relationship was observed for many of these BFRs, with higher quantiles associated with an increased risk of periodontitis. WQS regression identified PBDE-183 (38.60%), PBDE-153 (21.20%), PBDE-209 (14.40%), and PBDE-99 (11.90%) as the BFRs with the largest weights contributing to the overall mixture effect on periodontitis risk. BKMR analysis further supported the positive association between serum BFRs and periodontitis, with most individual BFRs showing a positive trend, except for PBDE-153. Restricted cubic spline analysis revealed a generally increasing probability of periodontitis with increasing concentrations of BFRs, albeit with some nonlinear patterns for certain compounds. CONCLUSION: In conclusion, this study provides compelling evidence of a significant association between exposure to brominated flame retardants (BFRs) and an increased risk of periodontitis in a nationally representative sample of U.S. adults. Elevated serum levels of several BFRs, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153, were found to be positively associated with periodontitis, exhibiting a dose-response relationship.
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Exposición a Riesgos Ambientales , Retardadores de Llama , Éteres Difenilos Halogenados , Periodontitis , Retardadores de Llama/análisis , Humanos , Adulto , Femenino , Éteres Difenilos Halogenados/sangre , Periodontitis/epidemiología , Periodontitis/inducido químicamente , Periodontitis/sangre , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/sangre , Anciano , Teorema de Bayes , Adulto JovenRESUMEN
In recent years, various transition metal compounds have been extensively studied to deal with the problems of slow reaction kinetics and the shuttle effect of lithium-sulfur (Li-S) batteries. Nevertheless, their catalytic performance still needs to be further improved by enhancing intrinsic catalytic activity and enriching active sites. Doping is an effective means to boost the catalytic performance through adjusting the electron structure of the catalysts. Herein, the electron structure of CoSe2 is adjusted by doping P, S with different p electron numbers and electronegativity. After S doping (S-CoSe2), the content of Co2+ increases, and charge is redistributed. Furthermore, more electrons are transferred between Li2S4/Li2S and S-CoSe2, and optimal Co-S bonds are formed between them with optimized d-p orbital hybridization, making the bonds of Li2S4/Li2S the longest and easy to break and decompose. Consequently, the Li-S batteries with the S-CoSe2-modified separator achieve improved rate performance and cycling performance, benefiting from the better bidirectional catalytic activity. This work will provide reference for the selection of the anion doping element to enhance the catalytic effect of transition metal compounds.
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The utilisation of coated controlled-release fertilizers (CRFs) leads to the persistence of residual plastic films in agricultural soils, posing a potential threat to crop health. This study investigates the impacts of four residual films (0.39â¯%, w/w) derived from CRFs in soil, including petrochemical polyether, bio-based polyether, castor oil polyester, and wheat straw polyester polyurethane on wheat growth. This study found that PecPEUR significantly reduced wheat plant height, stem diameter, leaf area, and aboveground fresh weight by 24.8â¯%, 20.2â¯%, and 25.7â¯%. Through an in-depth exploration of transcriptomics and metabolomics, it has been discovered that all residual films disrupted glycolysis-related metabolic pathways in wheat roots, affecting seedling growth. Among them, PecPEUR significantly reduced the fresh weight of aboveground parts by 20.5â¯%. In contrast, polyester polyurethane residue had no discernible impact on aboveground wheat growth. This was attributed to the enrichment of wheat root genes in jasmonic acid and γ-aminobutyric acid metabolic pathways, thus mitigating oxidative stress, enhancing stress resistance, and ensuring normal plant growth. This study, for the first time, provides comprehensive insights into the effects of polyurethane film residue on wheat seedling growth, underscoring its potential as a promising alternative to conventional plastics in soil.
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Metabolómica , Microplásticos , Poliuretanos , Contaminantes del Suelo , Triticum , Poliuretanos/química , Triticum/efectos de los fármacos , Triticum/crecimiento & desarrollo , Triticum/genética , Contaminantes del Suelo/toxicidad , Microplásticos/toxicidad , Transcriptoma/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/efectos de los fármacos , Fertilizantes , Suelo/químicaRESUMEN
Extracellular vesicles (EVs) act as mediators for intercellular transfer of Aß and tau proteins, promoting the propagation of these pathological misfolded proteins throughout the brain in Alzheimer's disease (AD). Levels of blood exosomal Aß42, total Tau (t-Tau) and phosphorylated Tau (p-Tau) had a high correlation with their concentrations in cerebrospinal fluid (CSF), demonstrating that exosomal biomarkers have equal contribution as those in CSF for the diagnosis of AD. We aimed to comprehensively characterize the proteome of plasma-derived EVs to identify differentially expressed proteins (DEPs) and pathways in AD. Tandem mass tag (TMT) labeled quantitative proteomics was applied to analyze plasma-derived EV proteins in 9 AD patients and 9 healthy controls. 335 proteins were quantified, and 12 DEPs were identified including seven upregulated proteins and five down-regulated proteins. Oligomerized Aß1-42 induced SH-SY5Y cell damage model was built to mimic the pathological changes of AD, and small interfering RNA (siRNA) against S100A8 was used to knock down S100A8 expression. Results displayed S100A8 was down regulated in plasma-derived EVs from AD patients, while enriched in EVs derived from Aß1-42-induced SH-SY5Y cells. Furthermore, Aß1-42-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aß levels in cell lysate and EVs, especially in EVs. SIGNIFICANCE: The investigation aimed to comprehensively characterize the proteome of plasma-derived EVs to identify DEPs and potential biomarker of AD. S100A8 was found down regulated in plasma-derived EVs from AD patients using TMT labeled quantitative proteomics. The diagnostic value of S100A8 was also confirmed using receiver operating characteristic curve (ROC) analysis. Furthermore, Aß1-42-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aß levels in cell lysate and EVs, especially in EVs. The preliminary findings suggest that suppression of S100A8 expression inhibits Aß aggregation both in cell lysate and EVs from Aß1-42-induced SH-SY5Y cells, and S100A8 more likely regulates Aß aggregation via EVs. Therefore, plasma-derived EV S100A8 might be a potential biomarker of AD. Manipulation of S100A8 expression may be a novel therapeutic strategy in the treatment of AD.
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Enfermedad de Alzheimer , Biomarcadores , Calgranulina A , Vesículas Extracelulares , Proteómica , Humanos , Enfermedad de Alzheimer/metabolismo , Biomarcadores/metabolismo , Proteómica/métodos , Masculino , Vesículas Extracelulares/metabolismo , Femenino , Anciano , Calgranulina A/metabolismo , Línea Celular Tumoral , Péptidos beta-Amiloides/metabolismo , Persona de Mediana Edad , Proteoma/metabolismoRESUMEN
Herpes zoster (HZ), a common disease in older adults, affects their quality of life. Therefore, this study aimed to examine the blog posts of HZ-related information on social media platforms to analyze the attitudes and behaviors of residents toward the dissemination of health information. This research used content analysis to focus on Weibo, a representative social media in China, to analyze the content of 1866 blog posts related to herpes zoster (HZ) and herpes zoster vaccine (HZV). According to the consistency test by Cohen's Kappa, four themes were identified: (a) sources, (b) tones, (c) epidemiological information, and (d) extended parallel process model elements. The findings showed that most information on Weibo came from non-professionals, with a neutral tone, and showed the invisible pain of HZ and the effectiveness of HZV through the two largest aspects of prevention and aged protection in epidemiological information. However, current blog posts treat the older adult as invisible individuals, failing to acknowledge them as recipients of the information. Additionally, the cost of the vaccine acts as an invisible economic barrier, contributing to the dissemination of incorrect information about folk remedies. This impacts the older adult's acceptance of health information related to HZV. Thus, the way to share health information with the older adult needs to be improved in the future, and attention should be paid to the transmission of incorrect information to improve their vaccination rates and awareness of health management.
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Vacuna contra el Herpes Zóster , Herpes Zóster , Medios de Comunicación Sociales , Humanos , Medios de Comunicación Sociales/estadística & datos numéricos , Herpes Zóster/prevención & control , Herpes Zóster/epidemiología , China/epidemiología , Anciano , Masculino , Femenino , Persona de Mediana Edad , Dolor , Calidad de VidaRESUMEN
ABSTRACT: Parkinson's disease is the second most common progressive neurodegenerative disorder, and few reliable biomarkers are available to track disease progression. The proteins, DNA, mRNA, and lipids carried by exosomes reflect intracellular changes, and thus can serve as biomarkers for a variety of conditions. In this study, we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson's disease and the potential therapeutic roles of these proteins in Parkinson's disease. Using a tandem mass tag-based quantitative proteomics approach, we characterized the proteomes of plasma exosomes derived from individual patients, identified exosomal protein signatures specific to patients with Parkinson's disease, and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein. N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot. The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson's disease, but also decreased with increasing Hoehn-Yahr stage, suggesting that N-acetyl- alpha-glucosaminidase could be used to rapidly evaluate Parkinson's disease severity. Furthermore, western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with methyl-4-phenylpyridinium (MPP+) and cells overexpressing a-synuclein (α-syn) compared with control cells. Additionally, N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibited α-syn expression in MPP+-treated cells. Taken together, our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson's disease diagnosis, and that N-acetyl-alpha- glucosaminidase may reduce α-syn expression and MPP+-induced neurotoxicity, thus providing a new therapeutic target for Parkinson's disease.
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PURPOSE: This study aimed to explore the real experiences and needs of neonatal intensive care unit (NICU) preterm intergenerational caregivers for discharge preparation and provide a basis for nursing staff to formulate systemic and personalized health education plans and continuous nursing plans for preterm discharge. DESIGN AND METHODS: This was a descriptive qualitative study. An objective sampling method was used to select 16 intergenerational caregivers of preterm infants admitted to the NICU of tertiary obstetrics and gynecology hospitals in Zhejiang and Jilin provinces from December 2023 to February 2024. Semi-structured interviews were conducted on the day of discharge of the preterm infants and six weeks after discharge. Colaizzi's seven-step analysis method was used to analyze the interview data. RESULTS: Based on the existence, relatedness, and growth (ERG) theory, the discharge preparation experiences and needs of neonatal intergenerational caregivers in the NICU were summarized into three themes: psychological condition, care capacity condition, and multi-party support needs. CONCLUSIONS: In the process of hospital discharge preparation, intergenerational caregivers of premature infants in NICU have multiple needs, including enhancing nursing ability and obtaining psychological and multi-party support. It is helpful to take effective interventions to improve their readiness for discharge. PRACTICE IMPLICATIONS: The nursing staff should develop personalized discharge health education plans and continuous nursing plans to improve the level of discharge preparation. PATIENT OR PUBLIC CONTRIBUTIONS: There were no patient or public contributions.
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Cuidadores , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Alta del Paciente , Investigación Cualitativa , Humanos , Recién Nacido , Femenino , Masculino , Cuidadores/educación , Cuidadores/psicología , Adulto , Evaluación de Necesidades , China , Relaciones IntergeneracionalesRESUMEN
Stylo (Stylosanthes spp.) is an important pasture legume with strong aluminum (Al) resistance. However, the molecular mechanisms underlying its Al tolerance remain fragmentary. Due to the incomplete genome sequence information of stylo, we first conducted full-length transcriptome sequencing for stylo root tips treated with and without Al and identified three Snakin/GASA genes, namely, SgSnakin1, SgSnakin2, and SgSnakin3. Through quantitative RT-PCR, we found that only SgSnakin1 was significantly upregulated by Al treatments in stylo root tips. Histochemical localization assays further verified the Al-enhanced expression of SgSnakin1 in stylo root tips. Subcellular localization in both tobacco and onion epidermis cells showed that SgSnakin1 localized to the cell wall. Overexpression of SgSnakin1 conferred Al tolerance in transgenic Arabidopsis, as reflected by higher relative root growth and cell vitality, as well as lower Al concentration in the roots of transgenic plants. Additionally, overexpression of SgSnakin1 increased the activities of SOD and POD and decreased the levels of O2·- and H2O2 in transgenic Arabidopsis in response to Al stress. These findings indicate that SgSnakin1 may function in Al resistance by enhancing the scavenging of reactive oxygen species through the regulation of antioxidant enzyme activities.
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Aluminio , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno , Aluminio/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/efectos de los fármacos , Fabaceae/metabolismo , Fabaceae/genética , Fabaceae/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Peróxido de Hidrógeno/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/efectos de los fármacosRESUMEN
Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.
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BACKGROUND: The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus (MERS-CoV) infection, thereby providing a novel therapeutic strategy for managing the clinical treatment of inflammatory response caused by respiratory virus infection. METHODS: We investigated the development of MERS by infecting hDPP4 mice with hCoV-EMC (107 TCID50 [50% tissue culture infectious dose]) intranasally. We infected A549 cells with MERS-CoV, which concurrently interfered with IL-37, detecting the viral titer, viral load, and cytokine expression at certain points postinfection. Meanwhile, we administered IL-37 (12.5 µg/kg) intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5 days after infection to investigate the efficacy of IL-37 in MERS-CoV infection. RESULTS: The viral titer of MERS-CoV-infected A549 cells interfering with IL-37 was significantly reduced by 4.7-fold, and the viral load of MERS-CoV-infected hDPP4 mice was decreased by 59-fold in lung tissue. Furthermore, the administration of IL-37 suppressed inflammatory cytokine and chemokine (monocyte chemoattractant protein 1, interferon-γ, and IL-17A) expression and ameliorated the infiltration of inflammatory cells in hDPP4 mice. CONCLUSION: IL-37 exhibits protective properties in severe pneumonia induced by MERS-CoV infection. This effect is achieved through attenuation of lung viral load, suppression of inflammatory cytokine secretion, reduction in inflammatory cell infiltration, and mitigation of pulmonary injury.
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Layered transition metal oxides are highly promising host materials for K ions, owing to their high theoretical capacities and appropriate operational potentials. To address the intrinsic issues of KxMnO2 cathodes and optimize their electrochemical properties, a novel P3-type oxide doped with carefully chosen cost-effective, electrochemically active and multi-functional elements is proposed, namely K0.57Cu0.1Fe0.1Mn0.8O2. Compared to the pristine K0.56MnO2, its reversible specific is increased from 104 to 135â mAh g-1. In addition, the Cu and Fe co-doping triples the capacity under high current densities, and contributes to long-term stability over 500â cycles with a capacity retention of 68 %. Such endeavor holds the potential to make potassium-ion batteries particularly competitive for application in sustainable, low-cost, and large-scale energy storage devices. In addition, the cathode is also extended for sodium storage. Facilitated by the interlayer K ions that protect the layered structure from collapsing and expand the diffusion pathway for sodium ions, the cathode shows a high reversible capacity of 144â mAh g-1, fast kinetics and a long lifespan over 1000â cycles. The findings offer a novel pathway for the development of high-performance and cost-effective sodium-ion batteries.
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Since its discovery, the role of the transcription factor, signal transducer and activator of transcription 3 (STAT3), in both normal physiology and the pathology of numerous diseases, including cancer, has been extensively studied. STAT3 is aberrantly activated in different types of cancer, fulfilling a critical role in cancer progression. The biological process, epithelialmesenchymal transition (EMT), is indispensable for embryonic morphogenesis. During the development of cancer, EMT is hijacked to confer motility, tumor cell stemness, drug resistance and adaptation to changes in the microenvironment. The aim of the present review was to outline recent advances in knowledge of the role of STAT3 in EMT, which may contribute to the understanding of the function of STAT3 in EMT in various types of cancer. Delineating the underlying mechanisms associated with the STAT3EMT signaling axis may generate novel diagnostic and therapeutic options for cancer treatment.
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Neoplasias , Factor de Transcripción STAT3 , Humanos , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Transducción de Señal/fisiología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Neoplasias/genéticaRESUMEN
Chinese liquor distillers' grain (CLDG) is a valuable and abundant by-product from traditional Chinese baijiu production, containing a diverse array of bioactive components that have attracted significant interest. Herein, a water-soluble polysaccharide, DGPS-2B, with a weight-average molecular weight of 37.3 kDa, was isolated from the alkali-extract fraction of CLDG. Methylation and NMR analysis identified that the primary constituents of DGPS-2B are arabinoxylans, with an arabinose-to-xylose ratio of 0.66. In an animal model of colitis, DGPS-2B treatment significantly altered the gut microbiota composition by increasing the SCFA-producing bacteria (e.g., Butyricicoccus) and reducing the mucin-degrading bacteria such as Muribaculaceae. This microbial shift resulted in elevated production of butyrate, acetate, and propionate, which subsequently suppressed NF-κB signaling, decreased the levels of IL-1ß, IL-6, and TNFα, and potentially inactivated Notch signaling. These multifaceted effects stimulated mucin 2 production, reduced inflammation and apoptosis in the gut epithelium, and ultimately alleviated colitis symptoms. Collectively, this study not only elucidates the purification and characterization of DGPS-2B from CLDG but also illuminates its anti-colitic properties and the underlying molecular mechanisms. These findings underscore the potential of DGPS-2B as a therapeutic intervention for managing inflammatory bowel disease and emphasize CLDG as a promising source for developing value-added products.
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Colitis , Agua , Xilanos , Xilanos/química , Xilanos/farmacología , Animales , Ratones , Agua/química , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Solubilidad , Microbioma Gastrointestinal/efectos de los fármacos , Grano Comestible/química , Masculino , Modelos Animales de Enfermedad , Peso MolecularRESUMEN
Arecoline, the predominant bioactive substance extracted from areca nut (AN), is the world's fourth most frequently used psychoactive material. Research has revealed that chewing AN can affect the central nervous system (CNS) and may lead to neurocognitive deficits that are possibly linked to the action of arecoline. However, the mechanism behind the neurotoxicity caused by arecoline remains unclear. This study aimed to investigate the neurotoxic effects of arecoline and its underlying mechanism. The results showed that arecoline caused cytotoxicity against HT22 cells in a dose-dependent manner and induced apoptosis by upregulating the expression of pro-apoptotic caspase and Bcl-2 family proteins. Furthermore, arecoline escalated intracellular reactive oxygen species (ROS) levels and Ca2+ concentration with increasing doses, thereby motivating endoplasmic reticulum stress (ERS) and ERS-associated apoptotic protein expression. Additionally, the study found that arecoline attenuates intracellular antioxidant defense by inhibiting the translocation of NF-E2-related factor-2 (Nrf2) into the nucleus and decreasing downstream Heme oxygenase-1 (HO-1) levels. The specific inhibitor Sodium 4-phenylbutyrate (4-PBA) can dramatically attenuate arecoline-mediated cell apoptosis and ERS-associated apoptotic pathway expression by blocking ERS. The antioxidant N-Acetylcysteine (NAC) also effectively reverses the arecoline-mediated increase of ERS-related apoptotic pathway protein levels by scavenging intracellular ROS accumulation. In conclusion, this study suggests that arecoline induces neurotoxicity in HT22 cells via ERS mediated by oxidative stress- and Ca2+ disturbance, as well as by downregulation of the Nrf2/HO-1 pathway.
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Apoptosis , Arecolina , Estrés del Retículo Endoplásmico , Transducción de Señal , Animales , Ratones , Apoptosis/efectos de los fármacos , Arecolina/toxicidad , Calcio/metabolismo , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Plant residues are important sources of soil organic carbon in terrestrial ecosystems. The degradation of plant residue by microbes can influence the soil carbon cycle and sequestration. However, little is known about the microbial composition and function, as well as the accumulation of soil organic carbon (SOC) in response to the inputs of different quality plant residues in the desert environment. The present study evaluated the effects of plant residue addition from Pinus sylvestris var. mongolica (Pi), Artemisia desertorum (Ar) and Amorpha fruticosa (Am) on desert soil microbial community composition and function in a field experiment in the Mu Us Desert. The results showed that the addition of the three plant residues with different C/N ratios induced significant variation in soil microbial communities. The Am treatment (low C/N ratio) improved microbial diversity compared with the Ar and Pi treatments (medium and high C/N ratios). The variations in the taxonomic and functional compositions of the dominant phyla Actinobacteria and Proteobacteria were higher than those of the other phyla among the different treatments. Moreover, the network links between Proteobacteria and other phyla and the CAZyme genes abundances from Proteobacteria increased with increasing residue C/N, whereas those decreased for Actinobacteria. The SOC content of the Am, Ar and Pi treatments increased by 45.73%, 66.54% and 107.99%, respectively, as compared to the original soil. The net SOC accumulation was positively correlated with Proteobacteria abundance and negatively correlated with Actinobacteria abundance. These findings showed that changing the initial quality of plant residue from low C/N to high C/N can result in shifts in taxonomic and functional composition from Actinobacteria to Proteobacteria, which favors SOC accumulation. This study elucidates the ecophysiological roles of Actinobacteria and Proteobacteria in the desert carbon cycle, expands our understanding of the potential microbial-mediated mechanisms by which plant residue inputs affect SOC sequestration in desert soils, and provides valuable guidance for species selection in desert vegetation reconstruction.
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Clima Desértico , Microbiología del Suelo , Ecosistema , Carbono/análisis , Carbono/metabolismo , Suelo/química , Secuestro de Carbono , Microbiota , Bacterias/clasificación , Bacterias/genéticaRESUMEN
Introduction: Ovulation dysfunction is now a widespread cause of infertility around the world. Although the impact of immune cells in human reproduction has been widely investigated, systematic understanding of the changes of the immune atlas under female ovulation remain less understood. Methods: Here, we generated single cell transcriptomic profiles of 80,689 PBMCs in three representative statuses of ovulation dysfunction, i.e., polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and menopause (MENO), and identified totally 7 major cell types and 25 subsets of cells. Results: Our study revealed distinct cluster distributions of immune cells among individuals of ovulation disorders and health. In patients with ovulation dysfunction, we observed a significant reduction in populations of naïve CD8 T cells and effector memory CD4 T cells, whereas circulating NK cells and regulatory NK cells increased. Discussion: Our results highlight the significant contribution of cDC-mediated signaling pathways to the overall inflammatory response within ovulation disorders. Furthermore, our data demonstrated a significant upregulation of oxidative stress in patients with ovulation disorder. Overall, our study gave a deeper insight into the mechanism of PCOS, POI, and menopause, which may contribute to the better diagnosis and treatments of these ovulatory disorder.
Asunto(s)
Infertilidad Femenina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/diagnóstico , Transcriptoma , Ovulación/genética , Infertilidad Femenina/terapiaRESUMEN
Importance: Antenatal corticosteroid treatment of individuals with singletons at risk for delivery during the late-preterm period has been academically recommended. However, the evidence on the use of antenatal corticosteroid treatment for twins at risk for delivery during the late-preterm period is still lacking. Objective: To evaluate whether antenatal corticosteroid treatment during the late-preterm period in twin pregnancies was associated with a lower risk of newborn morbidity. Design, Setting, and Participants: This retrospective cohort study of twin pregnancies delivered from February 1, 2013, to September 30, 2020, in a university-affiliated hospital in China included 1974 individuals with twin pregnancies who were at risk for late preterm birth (34 weeks and 0 days to 36 weeks and 6 days of gestation). Data were analyzed from June 30 to July 13, 2023. Exposures: Antenatal corticosteroid treatment during the late-preterm period. Main Outcomes and Measures: The primary outcome measure was composite neonatal respiratory morbidity, defined as at least 1 of the following postnatal occurrences in at least 1 neonate of the twins: respiratory distress syndrome, mechanical ventilation, surfactant administration, transferred with respiratory complications, or neonatal death. Propensity score overlap weighting was used to analyze the association between antenatal corticosteroid treatment and the risk of neonatal outcomes. Results: The study population consisted of 1974 individuals with twin pregnancies, including 303 (15.3%; mean [SD] maternal age, 30.8 [4.2] years) who received antenatal corticosteroid treatment and 1671 (84.7%; mean [SD] maternal age, 31.2 [4.0] years) who did not receive antenatal corticosteroid treatment. The propensity score overlap weighting showed no significant differences between the antenatal corticosteroid treatment group and the no-antenatal corticosteroid treatment group in the risk of neonatal primary outcome (29 of 303 [9.6%] vs 41 of 1671 [2.5%]; weighted odds ratio, 1.27 [95% CI, 0.60-2.76]). None of the subgroup interaction tests were significant for the neonatal primary outcome in terms of gestational age at delivery, year of delivery, chorionicity, at least 1 infant small for gestational age, intertwin growth discordance, and infant sex, and neither was the sensitivity analysis of using propensity score matching and a different administration-to-birth interval and treating twin infants as individuals. Conclusions and Relevance: This cohort study found insufficient evidence that antenatal corticosteroid treatment during the late-preterm period in twin pregnancies could be associated with a lower risk of newborn morbidity. This new finding can provide a reference for clinical practice.