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1.
Int J Biol Macromol ; 279(Pt 2): 134866, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233159

RESUMEN

In this study, the PVA/starch blend films were prepared by dry melting method. The microstructure showed that the starch existed in the continuous PVA matrix in granular structure. When the amount of starch was 30 wt%, the tensile strength increased from 12.8 to 14.7 MPa, and the elastic modulus increased from 15.4 to 20.5 MPa, and the water absorption increased by about 2 %. The addition of starch increased the Tmax by 8.1-29.64 °C compared to pure PVA. Considering the mechanical, hydrophilic and optical properties of the blend films, PVA/starch at 7:3 was the most promising packaging material. Notably, the blend films exhibit great reusability and renewability. Overall, these findings highlight the potential of PVA/starch blend films as environmentally friendly materials with enhanced properties.

2.
Front Microbiol ; 15: 1467029, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296301

RESUMEN

Influenza B virus (IBV) stands as a paradox, often overshadowed by its more notorious counterpart, influenza A virus (IAV). Yet, it remains a captivating and elusive subject of scientific inquiry. Influenza B is important because it causes seasonal flu outbreaks that can lead to severe respiratory illnesses, including bronchitis, pneumonia, and exacerbations of chronic conditions like asthma. Limitations in the influenza B virus's epidemiological, immunological, and etiological evolution must be addressed promptly. This comprehensive review covers evolutionary epidemiology and pathogenesis, host-virus interactions, viral isolation and propagation, advanced molecular detection assays, vaccine composition and no animal reservoir for influenza B virus. Complex viral etiology begins with intranasal transmission of influenza B virus with the release of a segmented RNA genome that attacks host cell machinery for transcription and translation within the nucleus and the release of viral progeny. Influenza B virus prevalence in domesticated and wild canines, sea mammals, and birds is frequent, yet there is no zoonosis. The periodic circulation of influenza B virus indicates a 1-3-year cycle for monophyletic strain replacement within the Victoria strain due to frequent antigenic drift in the HA near the receptor-binding site (RBS), while the antigenic stability of Yamagata viruses portrays a more conservative evolutionary pattern. Additionally, this article outlines contemporary antiviral strategies, including pharmacological interventions and vaccination efforts. This article serves as a resource for researchers, healthcare professionals, and anyone interested in the mysterious nature of the influenza B virus. It provides valuable insights and knowledge essential for comprehending and effectively countering this viral foe, which continues to pose a significant public health threat.

3.
J Neurosurg ; : 1-11, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303301

RESUMEN

OBJECTIVE: Craniopharyngiomas (CPs) in adults are rare benign epithelial tumors, and few contemporary studies have explored outcomes after surgical treatment in elderly patients, especially with regard to endoscopic endonasal surgery (EES). METHODS: A retrospective cohort study was conducted on patients aged ≥ 18 years with CP who were treated with EES from 2013 to 2022. The cohort was divided into nonelderly (18-64 years) and elderly (≥ 65 years) groups based on age. Various parameters, including patient and tumor characteristics, surgical outcomes, complications, and follow-up, were compared between the two age groups. RESULTS: A total of 193 patients met the inclusion criteria, with 161 (83.4%) patients in the nonelderly group and 32 (16.6%) patients in the elderly group. Preoperatively, older patients were more likely to have memory impairment (4.3% vs 18.8%, p = 0.010), fatigue or decreased energy (9.3% vs 34.4%, p = 0.001), hypopituitarism (68.7% vs 90.6%, p = 0.012), or hydrocephalus (18% vs 40.6%, p = 0.005), and they were more likely asymptomatic (1.2% vs 9.4%, p = 0.033) and less likely to experience headache (57.8% vs 31.3%, p = 0.006). Patients in the elderly group had a longer symptom duration (median [IQR] 5 [10] months vs 9.5 [13] months, p = 0.001) and higher comorbidity scores (p < 0.001). Postoperatively, gross-total resection was achieved in 145 (90.1%) and 28 (87.5%) patients in the nonelderly and elderly groups, respectively. Older patients were more likely to develop pneumonia (5% vs 21.9%, p = 0.004). There were no significant differences in the extent of resection (p = 0.541), pathological subtypes (88.2% vs 75.0% adamantinomatous, p = 0.089), operation time (mean ± SD 307.8 ± 68.3 minutes vs 323.5 ± 86.0 minutes, p = 0.257), estimated blood loss (median [IQR] 300 [200] ml vs 300 [238] ml, p = 0.594), length of stay (median [IQR] 15 [8] days vs 15 [22] days, p = 0.964), perioperative mortality (2.5% vs 3.1%, p > 0.99), or postoperative severe hypothalamic dysfunction (37.9% vs 50.0%, p = 0.237) between the groups. Multivariate Cox regression analysis demonstrated that tumor calcification (HR 3.406, 95% CI 1.859-27.233, p = 0.038) and preoperative hydrocephalus (HR 3.688, 95% CI 1.310-10.386, p = 0.013) were independently associated with decreased survival. The median follow-up period in the elderly group was shorter (71 months vs 44 months, p = 0.001), and no recurrence was observed (7.1% vs 0%, p = 0.132). CONCLUSIONS: This study demonstrates that EES is a viable treatment option for older CP patients. With appropriate perioperative management, EES does not significantly increase mortality and, in selected populations, is well tolerated by patients.

4.
Food Chem ; 463(Pt 2): 141133, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39265302

RESUMEN

A new convenient method for identifying colorant compounds (CCs) in food matrices was developed using high-performance liquid chromatography with a diode array detector and quadrupole-time-of-flight mass spectrometer (HPLC-DAD-Q/TOF-MS) combined with theoretical calculations. A model sample containing three typical CCs was completely separated via HPLC-DAD. The obtained 3D ultraviolet-visible (UV-vis) spectra revealed the maximum absorption wavelengths (MAWs) of all CCs (yellow, 430 nm; red, 520 nm; blue, 620 nm) in the range of 400-800 nm, and their colors were determined based on their MAWs. Temporary structures of the CCs were obtained using Q/TOF-MS analysis. Theoretical calculations were then performed to obtain the theoretical MAWs and colors of the CCs according to their calculated UV-vis spectra based on temporary structures. The structures of the CCs were confirmed without the need for authoritative standards by comparing the consistency between their experimental and theoretical MAWs and colors. This method is particularly suitable for identifying CCs or compounds with UV-Vis absorption, including new compounds, compounds for which standards are difficult to obtain, and known compounds without reporting relevant molecular information.

5.
J Agric Food Chem ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39265547

RESUMEN

Simultaneous detection of the dynamic distribution of long-chain fatty acid ethyl esters (LCFAEEs) during Baijiu distillation is crucial for optimizing its flavor and health attributes. In this study, we synthesized a simple, cost-effective Fe3O4@NH2 adsorbent to simultaneously extract eight LCFAEEs from Baijiu. Through density functional theory and adsorption experiments, we elucidated 1,6-hexanediamine as a surface modifier, with the -NH2 groups providing adsorption sites for the LCFAEEs via hydrogen-bonding interactions and van der Waals forces. Additionally, we established the magnetic solid-phase extraction-GC-MS extraction technique combined with stable isotope dilution analysis to analyze LCFAEEs. This method revealed the dynamic distribution patterns of LCFAEEs during strong aroma-type Baijiu (SAB) distillation. We observed that the concentrations of the eight LCFAEEs gradually decreased with prolonged distillation and were significantly correlated with ethanol concentration. To ensure optimal flavor and clarity in SAB, it is recommended to select the heart-stage base Baijiu with an alcohol content of 58%-63%.

6.
Eur J Med Chem ; 278: 116794, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39226707

RESUMEN

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC50 value of 0.49 µM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aß42 aggregation. Moreover, the selected nuclide [18F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment.


Asunto(s)
Acetofenonas , Enfermedad de Alzheimer , Diseño de Fármacos , Imidazoles , Fármacos Neuroprotectores , Oximas , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Oximas/química , Oximas/farmacología , Oximas/síntesis química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/síntesis química , Animales , Relación Estructura-Actividad , Imidazoles/farmacología , Imidazoles/química , Imidazoles/síntesis química , Acetofenonas/química , Acetofenonas/farmacología , Acetofenonas/síntesis química , Estructura Molecular , Humanos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Acetilcolinesterasa/metabolismo , Relación Dosis-Respuesta a Droga , Ratas , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química
7.
J Hazard Mater ; 480: 135874, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39316915

RESUMEN

The amelioration of cadmium (Cd2+) toxicity in plants by ammonium (NH4+) has been widely investigated. However, the molecular mechanisms underpinning this amelioration have remained ambiguous. Here, we found that NH4+ significantly reduces Cd2+ accumulation and enhances antioxidant capacity by increasing ABA accumulation, which, in turn, improves Cd2+ tolerance in rice seedlings. A combination of qPCR, yeast-one-hybrid and dual-luciferase assays, and CUT&RUN-qPCR methods demonstrates that OsbZIP20 directly binds to the promoters of OsAPX2 and OsCATA, activating their transcription, and we show that the process requires phosphorylation modification of OsbZIP20 by OsSAPK9. Under Cd2+ stress, Osbzip20 and Ossapk9 mutants show reduced peroxidase and catalase activities, higher H2O2 accumulation, and reduced Cd2+ tolerance. In sum, our results elucidate a novel mechanism by which NH4+ enhances Cd2+ resistance, through ABA-SAPK9-bZIP20-APX2/CATA, offering a new strategy for improving Cd2+ resistance in rice.

8.
Org Biomol Chem ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39318223

RESUMEN

A convenient method for synthesizing ß-trifluoromethyl vinyl ethers and diethers through the base-mediated C-O coupling of (E)-1,2-dichloro-3,3,3-trifluoroprop-1-ene and phenols has been developed. Remarkably, the present process shows perfect regioselective and stereoselective yield of the Z/E isomers for ß-trifluoromethyl vinyl ethers with high efficiency. Additionally, ß-trifluoromethyl vinyl diethers with identical/diverse phenoxy groups were also obtained and the regulation of the product configuration was achieved. These reactions feature transition-metal-free conditions, wide substrate scope, and atom economy.

9.
Amino Acids ; 56(1): 56, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292313

RESUMEN

Lupus nephritis (LN) is an immunoinflammatory glomerulonephritis associated with renal involvement in systemic lupus erythematosus (SLE). Given the close relationship between plasma amino acids (AAs) and renal function, this study aimed to elucidate the plasma AA profiles in LN patients and identify key AAs and diagnostic patterns that distinguish LN patients from those with SLE and healthy controls. Participants were categorized into three groups: normal controls (NC), SLE, and LN. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to quantify AA levels in human plasma. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to identify key AAs. The diagnostic capacity of the models was assessed using receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) values. Significant alterations in plasma AA profiles were observed in LN patients compared to the SLE and NC groups. The OPLS-DA model effectively separated LN patients from the SLE and NC groups. A joint model using histidine (His), lysine (Lys), and tryptophan (Trp) demonstrated exceptional diagnostic performance, achieving an AUC of 1.0 with 100% sensitivity, specificity, and accuracy in predicting LN. Another joint model comprising arginine (Arg), valine (Val), and Trp also exhibited robust predictive performance, with an AUC of 0.998, sensitivity of 93.80%, specificity of 100%, and accuracy of 95.78% in distinguishing between SLE and LN. The joint forecasting models showed excellent predictive capabilities in identifying LN and categorizing lupus disease status. This approach provides a novel perspective for the early identification, prevention, treatment, and management of LN based on variations in plasma AA levels.


Asunto(s)
Aminoácidos , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Nefritis Lúpica/sangre , Nefritis Lúpica/diagnóstico , Femenino , Adulto , Masculino , Lupus Eritematoso Sistémico/sangre , Aminoácidos/sangre , Persona de Mediana Edad , Metabolómica/métodos , Espectrometría de Masas en Tándem/métodos , Curva ROC , Triptófano/sangre , Biomarcadores/sangre , Diagnóstico Diferencial
10.
Artículo en Inglés | MEDLINE | ID: mdl-39311935

RESUMEN

BACKGROUND: Osteoarthritis has become the predominant manifestation of arthritic conditions on a worldwide scale and serves as a significant instigator of pain, impairment, and increasing socio-economic strain on a global level. The ongoing discourse on the choice between total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) for patients suffering from anterior medial osteoarthritis continues to ignite scholarly controversy. Our objective was to assess and compare the clinical outcomes of UKA and TKA within the same patient, hereby offering a novel perspective on this topic. MATERIALS AND METHODS: Fifty-seven individuals who underwent TKA on one knee and UKA on the other knee at the Department of Orthopaedics, First Hospital of Hebei Medical University between March 2019 and March 2024 were analysed for this retrospective study. We conducted a comprehensive examination and evaluation of perioperative laboratory assessments, radiological examinations, knee functionality, contentment levels, and postoperative complications within the two groups. RESULTS: Following surgical procedures, levels of hemoglobin, red blood cells, and albumin were found to be elevated in the UKA group when compared to the TKA group (hemoglobin: 121.2 ± 12.54 vs. 110.1 ± 13.21 g/L; red blood cells: 4.0 ± 0.47 vs. 3.6 ± 0.42 *1012/L; albumin: 37.7 ± 5.66 vs. 35.3 ± 5.23 g/L). There is a significant difference in the hip-knee-ankle angles between the postoperative UKA group and the TKA group (5.3 ± 3.46° vs. 4.1 ± 2.86°, p < 0.05). There existed no notable disparity in postoperative visual analog scale, knee society score, and forgotten joint score between the two groups. However, a remarkable variance was observed in postoperative range of motion between the two groups (116.4 ± 5.96° vs. 108.4 ± 5.32°). CONCLUSION: We found that UKA resulted in less physical strain, less postoperative inflammatory response, improved joint mobility, although with less effective lower limb force line correction compared to TKA. Many patients have shown a preference for UKA and express higher levels of satisfaction with the procedure.

11.
Oral Dis ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39286942

RESUMEN

OBJECTIVES: The odd-skipped related transcription factor 1 (OSR1) gene exerts distinct regulatory effects on tumorigenesis and development in various cancer types. However, the precise role of OSR1 in oral squamous cell carcinoma (OSCC) remains to be elucidated. METHODS: GEPIA 2 and TCGA databases were utilized to analyze the OSR1 expression in head and neck squamous cell carcinoma (HNSC) patients and its impact on prognosis. Hematoxylin-eosin staining, immunohistochemistry, immunofluorescence, western blotting, and RT-qPCR were employed to detect the OSR1 expression in OSCC tissues and cells. Lentivirus transfection was utilized for overexpression and downexpression of OSR1 in OSCC. CCK8 cell proliferation assay, colony formation and cell scratch assay were conducted to investigate the effects of OSR1 on biological behavior of OSCC cells. Western blotting and RT-qPCR were applied to investigate the regulatory mechanism of OSR1 on AXIN2/ß-catenin signaling pathway. RESULTS: OSR1 expression was significantly decreased in HNSC patients, OSCC tissues and cells, leading to a decrease in 5-year survival rate. OSR1 overexpression inhibited the proliferation and migration of OSCC cells, and the AXIN2/ß-catenin signaling pathway was inhibited. Silencing OSR1 had the opposite effect. CONCLUSIONS: OSR1 functioned as a tumor suppressor gene in OSCC proliferation and migration by regulating the AXIN2/ß-catenin signaling pathway.

12.
Cancer Inform ; 23: 11769351241275877, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39238655

RESUMEN

Background: Ovarian cancer has brought serious threats to female health. CCAAT/enhancer binding proteins (C/EBPs) are key transcription factors involved in ovarian cancer. Therefore, comprehensive profiling C/EBPs in ovarian cancer is needed. Methods: A comprehensive analysis concerning C/EBPs in ovarian cancer was performed. Firstly, detailed expression of C/EBP family members was integrally retrieved and then confirmed using immunohistochemistry. The regulatory effects and transcription regulatory functions of C/EBPs were studied by using regulatory network analysis and enrichment analysis. Using survival analysis, receiver operating characteristic curve analysis, and target-disease association analysis, the predictive prognostic value of C/EBPs on survival and drug responsiveness was systematically evaluated. The effects of C/EBPs on tumor immune infiltration were also assessed. Results: Ovarian cancer tissues expressed increased CEBPA, CEBPB, and CEBPG but decreased CEBPD when compared with normal control tissues. The overall alteration frequency of C/EBPs in ovarian cancer was approaching 30%. C/EBP family members formed a reciprocal regulatory network involving carcinogenesis and had pivotal transcription regulatory functions. C/EBPs could affect survival of ovarian cancer and correlated with poor survival outcomes (OS: HR = 1.40, P = .0053 and PFS: HR = 1.41, P = .0036). Besides, expression of CEBPA, CEBPB, CEBPD, and CEBPE could predict platinum and taxane responsiveness of ovarian cancer. C/EBPs also affected immune infiltration of ovarian cancer. Conclusions: C/EBPs were closely involved in ovarian cancer and exerted multiple biological functions. C/EBPs could be exploited as prognostic and predictive biomarkers in ovarian cancer.

13.
Theranostics ; 14(13): 5102-5122, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267784

RESUMEN

Rationale: Extrachromosomal circular DNA is a hallmark of cancer, but its role in shaping the genome heterogeneity of urothelial bladder carcinoma (UBC) remains poorly understood. Here, we comprehensively analyzed the features of extrachromosomal circular DNA in 80 UBC patients. Methods: We performed whole-genome/exome sequencing (WGS/WES), Circle-Seq, single-molecule real-time (SMRT) long-read sequencing of circular DNA, and RNA sequencing (RNA-Seq) on 80 pairs of tumor and AT samples. We used our newly developed circular DNA analysis software, Circle-Map++ to detect small extrachromosomal circular DNA from Circle-Seq data. Results: We observed a high load and significant heterogeneity of extrachromosomal circular DNAs in UBC, including numerous single-locus and complex chimeric circular DNAs originating from different chromosomes. This includes highly chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. We also found that large tumor-specific extrachromosomal circular DNAs could influence genome-wide gene expression, and are detectable in time-matched urinary sediments. Additionally, we found that the extrachromosomal circular DNA correlates with hypermutation, copy number variation, oncogene amplification, and clinical outcome. Conclusions: Overall, our study provides a comprehensive extrachromosomal circular DNA map of UBC, along with valuable data resources and bioinformatics tools for future cancer and extrachromosomal circular DNA research.


Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Circular , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Humanos , ADN Circular/genética , Variaciones en el Número de Copia de ADN/genética , Secuenciación Completa del Genoma/métodos , Heterogeneidad Genética , Masculino , Femenino , Secuenciación del Exoma/métodos , Anciano , Mutación/genética
14.
Artículo en Inglés | MEDLINE | ID: mdl-39235983

RESUMEN

Alzheimer disease (AD) is a prevalent neurodegenerative disorder that affects synapses and leads to progressive cognitive decline. The role of N-methyl-D-aspartic acid (NMDA) receptors in the pathogenesis of AD is well-established as they contribute to excitotoxicity and neurodegeneration in the pathological process of extrasynaptic glutamate concentration. However, the therapeutic potential of the NMDA receptor antagonist memantine in rescuing synaptic damage is limited. Research indicates that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors also play a significant role in AD. Abnormal transcription, expression, and localization of AMPA receptors lead to synaptic dysfunction and damage, contributing to early cognitive impairment in AD patients. Understanding the impact of AMPA receptors on AD pathogenesis and exploring the potential for the development of AMPA receptor-targeting drugs are crucial. This review aims to consolidate recent research findings on AMPA receptors in AD, elucidate the current state of AMPA receptor research and lay the foundation for future basic research and drug development.

15.
Protoplasma ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240379

RESUMEN

The phytohormone abscisic acid (ABA) is an important regulator of plant growth, but its potential participation in the process of in vitro shoot regeneration has not to date been reported. Here, we found that ABA appeared to inhibit in vitro shoot regeneration. ABA represses the formation of stem cell niches, thereby reducing the shoot regeneration by localizing the expression of WUSCHEL (WUS). During in vitro shoot regeneration, enrichment of H3K9ac in the specific region of WUS is a necessary event for its activation which could be inhibited by exogenous ABA. These findings reveal the potential function, as well as the possible way of ABA in regulating de novo shoot regeneration in Arabidopsis.

16.
Echocardiography ; 41(9): e15921, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39254093

RESUMEN

OBJECTIVE: The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. METHODS: STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. RESULTS: A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2 ± 9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr < 33.45% had more adverse long-term outcomes (log rank p < .0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p = .010). CONCLUSION: Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.


Asunto(s)
Ecocardiografía , Atrios Cardíacos , Lupus Eritematoso Sistémico , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Pronóstico , Ecocardiografía/métodos , Persona de Mediana Edad , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/sangre , Función del Atrio Derecho/fisiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/etiología , Estudios de Seguimiento
17.
CNS Neurosci Ther ; 30(9): e70024, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39218798

RESUMEN

AIMS: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression. METHODS: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. RESULTS: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. CONCLUSIONS: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.


Asunto(s)
Astrocitos , Diabetes Mellitus Tipo 2 , Regulación hacia Abajo , Transportador 2 de Aminoácidos Excitadores , Hipocampo , Ratones Endogámicos C57BL , Complicaciones Cognitivas Postoperatorias , Animales , Transportador 2 de Aminoácidos Excitadores/metabolismo , Transportador 2 de Aminoácidos Excitadores/biosíntesis , Transportador 2 de Aminoácidos Excitadores/genética , Astrocitos/metabolismo , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/metabolismo , Hipocampo/metabolismo , Ratones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Transgénicos
18.
CNS Neurosci Ther ; 30(8): e14902, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39138637

RESUMEN

AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.


Asunto(s)
Delirio , MicroARNs , Neuronas , Complicaciones Posoperatorias , ARN Circular , Sirtuina 3 , Animales , Sirtuina 3/metabolismo , Sirtuina 3/genética , Delirio/metabolismo , Ratones , MicroARNs/metabolismo , MicroARNs/genética , ARN Circular/metabolismo , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Masculino , Complicaciones Posoperatorias/metabolismo , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/efectos de los fármacos , Ratones Endogámicos C57BL , Fracturas de la Tibia/cirugía , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología
19.
Int J Biol Macromol ; 278(Pt 1): 134613, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39127284

RESUMEN

In the present study, the in vivo absorption and fecal excretion of a purified fraction of polysaccharides from the fruits of Lycium barbarum L. (LBPs-4) in rats were investigated by labelling LBPs-4 with fluorescein isothiocyanate (FITC). It was found that the fluorescent labeled LBPs-4 (LBPs-4-FITC) was not detected in the plasma within 24 h following the administration of a single dose of LBPs-4-FITC (100 mg/kg of body weight) to rats, indicating that LBPs-4 was hardly absorbed in its prototype form. Instead, a smaller fragment dissociated from LBPs-4-FITC was observed in feces and was accumulated in a time-dependent manner, suggesting that LBPs-4 was excreted into the feces with a form of degradation. Meanwhile, we observed that LBPs-4-FTIC could modulate the fecal bacterial community profile via increasing the relative abundances of Bacteroides ovatus and Alistipes and promote the production of acetic acid. Furthermore, the monoculture experiment confirmed that LBPs-4 could be metabolized into smaller fragment by B. ovatus, producing acetic acid. Collectively, our study provides information on the destiny of LBPs-4 after oral administration: non-absorbed but moved to the large intestine and catabolized by gut microbiota, especially B. ovatus.


Asunto(s)
Heces , Frutas , Lycium , Polisacáridos , Animales , Heces/química , Lycium/química , Ratas , Frutas/química , Polisacáridos/química , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Ratas Sprague-Dawley
20.
Sci Rep ; 14(1): 19889, 2024 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191800

RESUMEN

When IL-1 receptor antagonist (IL-1rn) is knocked out, mice have shown strain background dependent and major QTL regulated susceptibility to spontaneously inflammatory arthritis disease (SAD). The impact on bone properties resulting from the interactions of IL-1rn, genomic background strains, and the QTL locus, is unknown. Bone properties in the four specifically bred mouse strains with mutation of IL-1rn and variations in genomic components were investigated with high-resolution MicroCT and genomic analytical tools. Two congenic mouse strains were also measured to evaluate the influence on bone properties by a QTL in the region in chromosome 1. Our results reveal that several bone phenotypes, including bone mineral density (BMD), bone volume, tibial length, and cortical thickness of the tibia are different between wild type and IL-1rn knockout mice in both Balb/c and DBA/1 backgrounds, but IL-1rn knockout affects BMD differently between the two mouse strains. The absence of IL-1rn decreases BMD in Balb/c mice but increases BMD in DBA/1-/- mice compared to their respective wild type counterparts. A QTL transferred from the Balb/c genetic background which affects arthritis in congenic strains appears to also regulate BMD. While several genes, including Ctsg and Prg2, may affect BMD, Ifi202b is the most favored candidate gene for regulating BMD as well as SAD. In conclusion, the previously mentioned bone phenotypes are each influenced in different ways by the loss of IL-1ra when considered in mice from varying genomic backgrounds.


Asunto(s)
Densidad Ósea , Proteína Antagonista del Receptor de Interleucina 1 , Ratones Noqueados , Sitios de Carácter Cuantitativo , Animales , Ratones , Densidad Ósea/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/deficiencia , Ratones Endogámicos BALB C , Huesos/metabolismo , Huesos/diagnóstico por imagen , Huesos/patología , Ratones Endogámicos DBA , Masculino , Fenotipo , Microtomografía por Rayos X , Enfermedades Autoinflamatorias Hereditarias
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