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1.
Neural Regen Res ; 20(4): 1042-1057, 2025 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38989936

RESUMEN

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

3.
Sci Data ; 11(1): 712, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951502

RESUMEN

Riverine nitrogen is a pivotal determinant influencing water quality in inland and coastal waters. Despite the recognized utility, no spatially-explicit data on riverine nitrogen yield is available for large parts of the world, thus hindering our ability to identify the contributors to riverine nitrogen and understand aquatic nitrogen cycling. To fill the data gap for the United States, here we (1) compiled 294,996 total nitrogen (TN), 225,827 nitrate (NO3-), 204,015 ammonium (NH4+), and 158,837 total organic nitrogen (TON) concentrations, with concurrent streamflow data, across the Conterminous United States (CONUS), (2) estimated riverine nitrogen loads for over 1,800 hydrological stations, (3) derived the spatial distribution of annual riverine nitrogen yield by leveraging river and catchment connectivity information contained in the National Hydrography Dataset plus (NHDPlus), and (4) characterized nonpoint-source TN loads by excluding point-source loads. This new spatial dataset quantifies spatial sources of nitrogen yield from point and non-point sources (e.g., up to 36% from point sources across the U.S.) and serves as ground-truthing to validate water quality models.

4.
Sci Data ; 11(1): 788, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39019901

RESUMEN

Long-term streamflow observations contain essential information for understanding hydrological changes and managing water resources. A continental-scale dataset or analysis of temporal streamflow change is still lacking across hydrologic gauges in the Conterminous United States (CONUS). Here, we compiled 70 years of streamflow records from 1951 to 2021 at ~ 8000 hydrologic stations across the CONUS and characterized temporal trends, regime shifts, and extreme events using a Bayesian time series analysis algorithm. We found that the occurrences of sudden streamflow changes (e.g., regime shifts and extreme events) have been increasing with time across the CONUS. In addition, we derived 181 streamflow indicators that are valuable for hydrological and biological applications, such as the duration and frequency of high or low streamflow events. The Mississippi River Basin, especially the middle and lower parts, was a hot spot of high-frequency high-flow events. Overall, we anticipate the dataset generated here offers valuable information for understanding and quantifying changes in water resources across the CONUS.

5.
Front Cardiovasc Med ; 11: 1373480, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911515

RESUMEN

Background: Previous studies have indicated a strong link between blood metabolites and hypertension, however the causality of metabolites and hypertension is unknown. Methods: Two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between 486 blood metabolites and essential hypertension (EHT). Blood metabolite GWAS data was utilized as the exposure, with EHT GWAS data as the outcome. To further verify the results, another different source of EHT GWAS data was repeatedly analyzed. The major MR analytic approach used to determine causality was inverse variance weighted (IVW), with MR-Egger, Weighted Median, and MR-PRESSO models serving as supplements. We used the Cochran Q test to examine heterogeneity. Horizontal pleiotropy was examined using MR-Egger intercept and MR-PRESSO global test. The MR Steiger test confirmed the causal relationship between blood metabolites and EHT. Results: In this study, nine blood metabolites associated with EHT were preliminarily identified by MR analysis, including four known metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid, creatine, hexadecanedioate) and five unknown metabolites. Then another source of EHT GWAS data was repeatedly analyzed for further verification, and two overlapped metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid) were found. There was a negative correlation between N-acetylornithine and EHT (OR = 0.987, 95% CI = 0.980-0.993, P = 1.01 × 10-4), Cochran's Q test suggested there was no heterogeneity (Q = 31.7586, P = 0.1331), MR-Egger intercept and MR-PRESSO global test suggested there was no horizontal pleiotropy (P > 0.05), Leave-one-out analysis indicated that no single single-nucleotide polymorphism (SNP) had a significant effect on the results, and MR Steiger test confirmed that the direction of causality was correct (P < 0.001). There was a negative correlation between X-12510-2-aminooctanoic acid and EHT (OR = 0.982, 95% CI = 0.972-0.993, P = 0.0017), and there was no evidence of heterogeneity or pleiotropy in multiple sensitivity analyses. Conclusion: The study discovered some blood metabolites causally linked to EHT, which might lead to new understandings of the pathophysiology of hypertension.

6.
Infect Dis Model ; 9(3): 975-994, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38881537

RESUMEN

Parameter identification involves the estimation of undisclosed parameters within a system based on observed data and mathematical models. In this investigation, we employ DAISY to meticulously examine the structural identifiability of parameters of a within-host SARS-CoV-2 epidemic model, taking into account an array of observable datasets. Furthermore, Monte Carlo simulations are performed to offer a comprehensive practical analysis of model parameters. Lastly, sensitivity analysis is employed to ascertain that decreasing the replication rate of the SARS-CoV-2 virus and curbing the infectious period are the most efficacious measures in alleviating the dissemination of COVID-19 amongst hosts.

7.
Wei Sheng Yan Jiu ; 53(3): 455-464, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38839588

RESUMEN

OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk. METHODS: Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 ℃ for 30 min, then incubated with papain and acid phosphatase at 45 ℃ for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 µm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method. RESULTS: 11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 µg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 µg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected. CONCLUSION: The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.


Asunto(s)
Leche , Espectrometría de Masas en Tándem , Leche/química , Espectrometría de Masas en Tándem/métodos , Animales , Cromatografía Líquida de Alta Presión/métodos , Niacinamida/análisis , Riboflavina/análisis , Nutrientes/análisis , Ácido Pantoténico/análisis , Bovinos , Piridoxina/análisis , Niacina/análisis , Carnitina/análisis
8.
J Environ Manage ; 365: 121588, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38941851

RESUMEN

There have been notable changes in precipitation patterns on the Loess Plateau (LP) of China in recent decades, and numerous attribution studies have focused on sea surface temperature anomalies and atmospheric circulation changes induced by aerosols and greenhouse gases emission. However, the influences of global land use and land cover change (LULCC) as an important forcing factor in the climate system on regional precipitation remains poorly understood. In this study, we quantified the impacts of LULCC on precipitation and the water vapor budget in the LP region, utilizing data from LULCC forcing experiments conducted by the sixth phase of the Coupled Model Intercomparison Project (CMIP6). Although global LULCC forcing exerted a negative effect on long-term mean precipitation on the LP region from 1850 to 2014, the different response characteristics were detected during different time periods. The global LULCC caused a decrease of 14 mm in annual precipitation during the period of 1850-1960. Conversely, from 1961 to 2014, it led to an increase of 6.4 mm, which is largely attributed to the enhanced water vapor transport along the southern boundary and westerly belt of the LP region. Moreover, from the perspective of the net water vapor balance of the entire LP, although LULCC caused net water vapor export during both periods 1850-1960 and 1961-2014, the export during the latter period (0.20 × 104 kg s-1) was smaller than that during the former period (0.28 × 104 kg s-1), indicating that the global expansion of grassland and cropland, along with the continuous rise in the leaf area index from 1961 to 2014, contributed to retaining more water vapor within the LP, which in turn was more favorable for precipitation. These findings provide valuable insights into the reasons behind precipitation variations in the LP region, emphasizing that global vegetation restoration and greening play a significant role in improving precipitation in ecologically fragile areas.


Asunto(s)
Vapor , China , Cambio Climático , Lluvia
9.
Heliyon ; 10(10): e30923, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38778950

RESUMEN

Remotely sensed products are often used in watershed modeling as additional constraints to improve model predictions and reduce model uncertainty. Remotely sensed products also enabled the spatial evaluation of model simulations due to their spatial and temporal coverage. However, their usability is not extensively explored in various regions. This study evaluates the effectiveness of incorporating remotely sensed evapotranspiration (RS-ET) and leaf area index (RS-LAI) products to enhance watershed modeling predictions. The objectives include reducing parameter uncertainty at the watershed scale and refining the model's capability to predict the spatial distribution of ET and LAI at sub-watershed scale. Using the Soil and Water Assessment Tool (SWAT) model, a systematic calibration procedure was applied. Initially, solely streamflow data was employed as a constraint, gradually incorporating RS-ET and RS-LAI thereafter. The results showed that while 14 parameter sets exhibit satisfactory performance for streamflow and RS-ET, this number diminishes to six with the inclusion of RS-LAI as an additional constraint. Furthermore, among these six sets, only three effectively captured the spatial patterns of ET and LAI at the sub-watershed level. Our findings showed that leveraging multiple remotely sensed products has the potential to diminish parameter uncertainty and increase the credibility of intra-watershed process simulations. These results contributed to broadening the applicability of remotely sensed products in watershed modeling, enhancing their usefulness in this field.

10.
Cell Death Discov ; 10(1): 224, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724500

RESUMEN

Spinal cord injury (SCI) remains a formidable challenge, lacking effective treatments. Following SCI, neural stem cells (NSCs) migrate to SCI sites, offering a potential avenue for nerve regeneration, but the effectiveness of this intrinsic repair mechanism remains suboptimal. Salidroside has demonstrated pro-repair attributes in various pathological conditions, including arthritis and cerebral ischemia, and the ability to curtail early-stage inflammation following SCI. However, the specific role of salidroside in the late-stage repair processes of SCI remains less defined. In this investigation, we observed that continuous salidroside treatment in SCI mice improved motor function recovery. Immunofluorescence-staining corroborated salidroside's capacity to stimulate nerve regeneration and remyelination, suppress glial scar hyperplasia, reduce the activation of neurotoxic A1 astrocytes, and facilitate NSCs migration towards the injured region. Mechanistically, in vitro experiments elucidated salidroside's significant role in restraining astrocyte proliferation and A1 polarization. It was further established that A1 astrocytes hinder NSCs proliferation while inducing their differentiation into astrocytes. Salidroside effectively ameliorated this inhibition of NSCs proliferation through diminishing c-Jun N-terminal kinase (JNK) pathway phosphorylation and restored their differentiation into neurons by suppressing the signal transducer and activator of transcription 3 (STAT3) pathway. In summary, our findings suggest that salidroside holds promise as a therapeutic agent for traumatic SCI treatment.

11.
Food Chem ; 454: 139733, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38805923

RESUMEN

Milk phospholipids have multiple health benefits, but the deficiency of detailed phospholipid profiles in dairy products brings obstacles to intake calculation and function evaluation of dairy phospholipids. In present study, 306 phospholipid molecular species were identified and quantified among 207 milk, yogurt and cream products using a HILIC-ESI-Q-TOF MS and a HILIC-ESI-QQQ MS. The phospholipid profiles of five mammals' milk show that camel milk contains the most abundant phosphatidylethanolamine, phosphatidylserine and sphingomyelin; cow, yak and goat milk have similar phospholipidomes, while buffalo milk contains abundant phosphatidylinositol. Fewer plasmalogens but more lyso-glycerolphospholipids were found in ultra-high-temperature (UHT) sterilized milk than in pasteurized milk, and higher proportions of lyso-glycerolphospholipid/total phospholipid were observed in both cream and skimmed/semi-skimmed milk than whole milk, indicating that UHT and skimming processes improve glycerolphospholipid degradation and phospholipid nutrition loss. Meanwhile, more diacyl-glycerolphospholipids and less of their degradation products make yogurt a better phospholipid resource than whole milk.


Asunto(s)
Leche , Fosfolípidos , Yogur , Animales , Fosfolípidos/análisis , Fosfolípidos/química , Leche/química , Yogur/análisis , Bovinos , Manipulación de Alimentos , Cabras , Productos Lácteos/análisis , Camelus , Búfalos/metabolismo
12.
Eur J Radiol ; 175: 111449, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38604093

RESUMEN

PURPOSE: Calf muscles play an important role in marathon race, and the incidence of injury is high in this process. This study prospectively quantified diffusion tensor metrics, muscle fat fraction (MFF) and cross-sectional area (CSA) of calf muscles induced by endurance exercise in amateur marathoners, and the potential mechanisms underlying the changes in these parameters were analyzed. METHOD: In this prospective study, 35 marathoners (27 males, 8 females; mean age (standard deviation, SD), 38.92 (4.83) years) and 26 controls (18 males, 8 females; mean age (SD), 38.35 (6.75) years) underwent magnetic resonance imaging (MRI) from September 2022 to March 2023. The diffusion tensor eigenvalues (λ1, λ2, λ3), radial diffusivity (RD), fractional anisotropy (FA), MFF and CSA of calf muscles were compared between marathoners and controls. A binary logistic regression model with gender correction was performed analyze the relationship between marathon exercise and DTI parameters, CSA and MFF of calf muscles. RESULTS: Interobserver agreement was good (κ = 0.71). The results of binary logistic regression model with gender correction showed that the regression coefficients of FA values in anterior group of calf (AC), soleus (SOL), medial gastrocnemius (MG) and lateral gastrocnemius (LG) were negative, and the odds ratios (OR) were 0.33, 0.45, 0.35, 0.05, respectively (P < 0.05). The OR of RD in SOL and λ2 in external group of calf (EC) were relatively higher, 3.74 and 3.26, respectively (P < 0.05). CSA was greater in SOL of marathoners, with an OR value of 1.00(P < 0.05). The MFF in AC and LG was lower in marathoners and OR of two indexes were -0.69 and -0.59, respectively (P < 0.05). CONCLUSIONS: Diffusion tensor imaging (DTI) combined with chemical shift-encoded sequence can noninvasively detect and quantify the adaptive changes of calf muscle morphology, microstructure and tissue composition induced by long-term running training in amateur marathoners.


Asunto(s)
Imagen de Difusión Tensora , Carrera de Maratón , Músculo Esquelético , Humanos , Imagen de Difusión Tensora/métodos , Masculino , Femenino , Músculo Esquelético/diagnóstico por imagen , Adulto , Estudios Prospectivos , Carrera de Maratón/fisiología , Pierna/diagnóstico por imagen , Adaptación Fisiológica
13.
Curr Protoc ; 4(4): e1011, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38648070

RESUMEN

Indentation testing is the most common approach to quantify mechanical brain tissue properties. Despite a myriad of studies conducted already, reported stiffness values vary extensively and continue to be subject of study. Moreover, the growing interest in the relationship between the brain's spatially heterogeneous microstructure and local tissue stiffness warrants the development of standardized measurement protocols to enable comparability between studies and assess repeatability of reported data. Here, we present three individual protocols that outline (1) sample preparation of a 1000-µm thick coronal slice, (2) a comprehensive list of experimental parameters associated with the FemtoTools FT-MTA03 Micromechanical Testing System for spherical indentation, and (3) two different approaches to derive the elastic modulus from raw force-displacement data. Lastly, we demonstrate that our protocols deliver a robust experimental framework that enables us to determine the spatially heterogeneous microstructural properties of (mouse) brain tissue. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Mouse brain sample preparation Basic Protocol 2: Indentation testing of mouse brain tissue using the FemtoTools FT-MTA03 Micromechanical Testing and Assembly System Basic Protocol 3: Tissue stiffness identification from force-displacement data.


Asunto(s)
Encéfalo , Animales , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Ratones , Módulo de Elasticidad , Fenómenos Biomecánicos , Pruebas Mecánicas
15.
Int Immunopharmacol ; 133: 112067, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38608444

RESUMEN

Silicosis is one of the most common and severe types of pneumoconiosis and is characterized by lung dysfunction, persistent lung inflammation, pulmonary nodule formation, and irreversible pulmonary fibrosis. The transdifferentiation of fibroblasts into myofibroblasts is one of the main reasons for the exacerbation of silicosis. However, the underlying mechanism of transcription factors regulating silicosis fibrosis has not been clarified. The aim of this study was to investigate the potential mechanism of transcription factor FOXF1 in fibroblast transdifferentiation in silica-induced pulmonary fibrosis. Therefore, a silicosis mouse model was established, and we found that FOXF1 expression level was significantly down-regulated in the silicosis group, and after overexpression of FOXF1 by adeno-associated virus (AAV), FOXF1 expression level was up-regulated, and silicosis fibrosis was alleviated. In order to further explore the specific regulatory mechanism of FOXF1 in silicosis, we established a fibroblasts transdifferentiation model induced by TGF-ß in vitro. In the model, the expression levels of SMAD2/3 and P-SMAD2/3 were up-regulated, but the expression levels of SMAD2/3 and P-SMAD2/3 were down-regulated, inhibiting transdifferentiation and accumulation of extracellular matrix after the overexpressed FOXF1 plasmid was constructed. However, after silencing FOXF1, the expression levels of SMAD2/3 and P-SMAD2/3 were further up-regulated, aggravating transdifferentiation and accumulation of extracellular matrix. These results indicate that the activation of FOXF1 in fibroblasts can slow down the progression of silicosis fibrosis by inhibiting TGF-ß/SMAD2/3 classical pathway, which provides a new idea for further exploration of silicosis treatment.


Asunto(s)
Transdiferenciación Celular , Fibroblastos , Fibrosis Pulmonar , Transducción de Señal , Silicosis , Factor de Crecimiento Transformador beta , Animales , Humanos , Masculino , Ratones , Transdiferenciación Celular/genética , Células Cultivadas , Modelos Animales de Enfermedad , Fibroblastos/citología , Fibroblastos/metabolismo , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Pulmón/patología , Ratones Endogámicos C57BL , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Dióxido de Silicio , Silicosis/complicaciones , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Proteína smad3/genética , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo
16.
Front Microbiol ; 15: 1331130, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38596370

RESUMEN

The gut-brain axis is evident in modulating neuropsychiatric diseases including autism spectrum disorder (ASD). Chromosomal 16p11.2 microduplication 16p11.2dp/+ is among the most prevalent genetic copy number variations (CNV) linked with ASD. However, the implications of gut microbiota status underlying the development of ASD-like impairments induced by 16p11.2dp/+ remains unclear. To address this, we initially investigated a mouse model of 16p11.2dp/+, which exhibits social novelty deficit and repetitive behavior characteristic of ASD. Subsequently, we conducted a comparative analysis of the gut microbial community and metabolomic profiles between 16p11.2dp/+ and their wild-type counterparts using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS). Our microbiota analysis revealed structural dysbiosis in 16p11.2dp/+ mice, characterized by reduced biodiversity and alterations in species abundance, as indicated by α/ß-diversity analysis. Specifically, we observed reduced relative abundances of Faecalibaculum and Romboutsia, accompanied by an increase in Turicibacter and Prevotellaceae UCG_001 in 16p11.2dp/+ group. Metabolomic analysis identified 19 significantly altered metabolites and unveiled enriched amino acid metabolism pathways. Notably, a disruption in the predominantly histamine-centered neurotransmitter network was observed in 16p11.2dp/+ mice. Collectively, our findings delineate potential alterations and correlations among the gut microbiota and microbial neurotransmitters in 16p11.2dp/+ mice, providing new insights into the pathogenesis of and treatment for 16p11.2 CNV-associated ASD.

17.
Bioact Mater ; 36: 157-167, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38463554

RESUMEN

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

18.
Microbiome ; 12(1): 66, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38549163

RESUMEN

BACKGROUND: Microdeletion of the human chromosomal region 16p11.2 (16p11.2 + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 + / -  syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 + / -  are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 + / - , as well as the underlying molecular mechanisms. RESULTS: Mice with the 16p11.2 + / -  showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. CONCLUSIONS: Our study reveals that 16p11.2 + / -  leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 + / -  mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome. Video Abstract.


Asunto(s)
Trastorno del Espectro Autista , Propionatos , Humanos , Ratones , Animales , Transmisión Sináptica , Hipocampo , Indoles
19.
PLoS One ; 19(2): e0298792, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38386660

RESUMEN

BACKGROUND AND AIM: The clinical outcome of endoscopy submucosal dissection with subsequent radiotherapy for esophageal squamous cell carcinoma remain unclear. In this study we aim to investigate the efficacy and safety of endoscopic submucosal dissection with adjuvant radiotherapy in the treatment of superficial esophageal squamous cell carcinoma involving the muscularis mucosae (T1a-MM) or the submucosa < 200 µm (T1b-SM1). METHODS: We analyzed 20 patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell carcinoma treated by endoscopic submucosal dissection from 2016 to 2020 in Lihuili Hospital, 9 patients received adjuvant radiotherapy (RT group) and 11 patients received did not (non-RT group). RESULTS: All 20 patients underwent en bloc resection, and both the vertical and horizontal margins were negative. There was no recurrence or lymph node metastasis in the RT group, and no serious complications or death were observed. In the non-RT group, 2 patients had local recurrence and 1 had distant metastasis. None of the 20 patients died of esophageal carcinoma. CONCLUSIONS: Adjuvant radiotherapy following endoscopic submucosal dissection may be a safe and effective method for the treatment of T1a-MM/T1b-SM1 superficial esophageal squamous cell carcinoma.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/radioterapia , Carcinoma de Células Escamosas de Esófago/cirugía , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Radioterapia Adyuvante/efectos adversos , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Resultado del Tratamiento
20.
Eur Spine J ; 33(2): 386-393, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38180515

RESUMEN

PURPOSE: The aim of this study was to translate and cross-culturally adapt the Core Outcome Measures Index for (COMI) into a Simplified Chinese version (COMI-SC) and to evaluate the reliability and validity of COMI-SC in patients with neck pain. METHODS: The COMI-neck was translated into Chinese according to established methods. The COMI-neck questionnaire was then completed by 122 patients with a hospital diagnosis of neck pain. Reliability was assessed by calculating Cronbach's alpha and intraclass correlation coefficient (ICC). Construct validity was assessed by correlating the COMI-neck with the Neck Pain and Disability Scale (NPDS), the Neck Disability Index (NDI), the VAS and the Short Form (36) Health Survey (SF-36). Using confirmatory factor analysis to validate the structural, convergent and discriminant validity of the questionnaire. RESULTS: The COMI-neck total scores were well distributed, with no floor or ceiling effects. Internal consistency was excellent (Cronbach's alpha = 0.861). Moderate to substantial correlations were found between COMI-neck and NPDS (r = 0.420/0.416/0.437, P < 0.001), NDI (r = 0.890, P < 0.001), VAS (r = 0.845, P < 0.001), as well as physical function (r = - 0.989, P < 0.001), physical role (r = - 0.597, P < 0.001), bodily pain (r = - 0. 639, P < 0.001), general health (r = - 0.563, P < 0.001), vitality (r = - 0.702, P < 0.001), social functioning (r = - 0.764, P < 0.001), role emotional (r = - 0.675, P < 0.001) and mental health (r = - 0.507, P < 0.001) subscales of the SF-36. An exploratory factor analysis revealed that the 3-factor loading explained 71.558% of the total variance [Kaiser-Mayer-Olkin (KMO) = 0.780, C2 = 502.82, P < 0.001]. CMIN/DF = 1.813, Tucker-Lewis index (TLI) = 0.966 (> 0.9), Comparative Fit Index (CFI) = 0.982 (> 0.9), Normed Fit Index (NFI) = 0.961 (> 0.9), RMSEA = 0.082 (< 0.5) indicating that the model fits well. CONCLUSION: COMI-neck was shown to have acceptable reliability and validity in patients with non-specific chronic neck pain and could be recommended for patients in mainland China. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.


Asunto(s)
Comparación Transcultural , Dolor de Cuello , Humanos , Dolor de Cuello/diagnóstico , Estudios Transversales , Reproducibilidad de los Resultados , Cuello , Encuestas y Cuestionarios , Psicometría , Evaluación de la Discapacidad
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