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1.
Exp Mol Med ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609519

RESUMO

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

2.
Animals (Basel) ; 14(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612332

RESUMO

Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.

3.
Neuroepidemiology ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599180

RESUMO

INTRODUCTION: We aimed to investigate the risk factors associated with post-stroke epilepsy (PSE) among patients with different subtypes of stroke, focusing on age-related risk and time-varying effects of stroke subtype on PSE development. METHODS: A retrospective, nationwide, population-based cohort study was conducted using Korean National Health Insurance Service-National Sample Cohort data. Patients hospitalized with newly diagnosed stroke from 2005 to 2015 were included and followed up for up to 10 years. The primary outcome was the development of PSE, defined as having a diagnostic code and a prescription for anti-seizure medication. Multivariable Cox proportional hazard models were used to estimate PSE hazard ratios (HRs), and time-varying effects were also assessed. RESULTS: A total of 8,305 patients with ischemic stroke, 1,563 with intracerebral hemorrhage (ICH), and 931 with subarachnoid hemorrhage (SAH) were included. During 10 years of follow-up, 4.6% of patients developed PSE. Among patients with ischemic stroke, significant risk factors for PSE were younger age (HR = 1.47), living in rural areas (HR = 1.35), admission through the emergency room (HR = 1.33), and longer duration of hospital stay (HR = 1.45). Time-varying analysis revealed elevated hazard ratios for ICH and SAH, particularly in the first two years following the stroke. The age-specific hazard ratios also showed an increased risk for those under the age of 65, with a noticeable decrease in risk beyond that age. CONCLUSION: The risk of developing PSE varies according to stroke subtype, age, and other demographic factors. These findings underscore the importance of tailored poststroke monitoring and management strategies to mitigate the risk of PSE.

4.
J Affect Disord ; 354: 619-626, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494140

RESUMO

BACKGROUND: Depression, migraine, insomnia, and fibromyalgia are reportedly comorbidities. Nevertheless, no study has evaluated the comorbidity of all four of these disorders. This study aimed to investigate the comorbidity of these four disorders. METHODS: Cross-sectional analyses were performed using data of the Circannual Change in Headache and Sleep study, an online nationwide population-based survey. Validated questionnaires were used to diagnose the disorders and measure quality of life. The change of clinical characteristics by addition of any comorbidity was analyzed using the Jonckheere-Terpstra trend test. RESULTS: The prevalence rates of depression, migraine, insomnia, and fibromyalgia were 7.2 %, 5.6 %, 13.3 %, and 5.8 %, respectively. Among the 3030 included participants, 494 (16.3 %), 164 (5.4 %), 40 (1.3 %), and 6 (0.2 %) had one, two, three, and four of these conditions, respectively. The number of headache days per 30 days (Jonckheere-Terpstra trend test, p = 0.011) and migraine-related disability (migraine disability assessment score, p = 0.021) increased with an increase in the number of comorbidities but not with the intensity of headache (visual analog scale, p = 0.225) among participants with migraine. The severity of insomnia (Insomnia Severity Index, p < 0.001) and fibromyalgia (fibromyalgia severity score, p = 0.002) increased with additional comorbidities; however, depression (Patient Health Questionnaire-9, p = 0.384) did not show such an increase. LIMITATIONS: The diagnoses of conditions were based on self-reported questionnaires. CONCLUSIONS: The findings confirmed significant comorbidity between depression, migraine, insomnia, and fibromyalgia. Health professionals should be aware of the probable comorbidity of depression, migraine, insomnia, and fibromyalgia when caring for individuals with any of these four disorders.


Assuntos
Fibromialgia , Transtornos de Enxaqueca , Distúrbios do Início e da Manutenção do Sono , Humanos , Fibromialgia/epidemiologia , Depressão/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Qualidade de Vida , Comorbidade , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/diagnóstico , Cefaleia
5.
Sci Rep ; 14(1): 6007, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472388

RESUMO

Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1-2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment-adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking-was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.


Assuntos
Café , Transtornos de Enxaqueca , Humanos , Estudos Transversais , Transtornos de Enxaqueca/epidemiologia , Cefaleia/epidemiologia , Comorbidade
6.
J Sport Health Sci ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428732

RESUMO

BACKGROUND: Acute lateral ankle sprains (ALAS) are associated with long-term impairments and instability tied to altered neural excitability. Arthrogenic muscle inhibition (AMI) has been observed in this population; however, relationships with injury-related impairments are unclear, potentially due to the resting, prone position in which AMI is typically measured. Assessing AMI during bipedal stance may provide a better understanding of this relationship. METHODS: AMI was assessed in 38 young adults (19 ALAS within 72 h of injury: 10 males, 21.4 ± 2.7 years; 19 healthy controls: 10 males, 21.9 ± 2.2 years; mean ± standard deviation) using the Hoffmann reflex during bipedal stance. Electrical stimulation was administered to identify the maximal H-reflex (Hmax) and maximal motor response (Mmax) from the soleus, fibularis longus, and tibialis anterior muscles. The primary outcome measure was the Hmax/Mmax ratio. Secondary outcomes included acute symptoms (pain and swelling), postural control during bipedal stance, and self-reported function. RESULTS: No significant group-by-limb interactions were observed for any muscle. However, a significant group main effect was observed in the soleus muscle, F(1,35) = 6.82, p = 0.013, indicating significantly lower Hmax/Mmax ratios following ALAS (0.38 ± 0.20) compared to healthy controls (0.53 ± 0.16). Furthermore, lower Hmax/Mmax ratios in the soleus significantly correlated with acute symptoms and self-reported function but not with postural control. CONCLUSION: This study supports previous evidence of AMI in patients with ALAS, providing insight into neurophysiologic impacts of musculoskeletal injury. Our results suggest that assessing AMI in a standing position following acute injury may provide valuable insight into how AMI develops and guide potential therapeutic options to curb and offset the formation of joint instability.

7.
J Int Med Res ; 52(3): 3000605241233514, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38501996

RESUMO

OBJECTIVE: To compare the kinematic effects of two widely-used prefabricated ankle-foot orthoses (AFOs), the Dyna Ankle (DA) and UD Flex (UD), on the gait cycle of patients with hemiplegia due to cerebral palsy or acquired brain injury. METHODS: This was a retrospective cohort study involving 29 patients. Gait analysis results were assessed under three conditions: barefoot, with the DA, and with the UD. Friedman tests and post hoc analysis with Bonferroni correction were performed to assess differences between the three conditions. RESULTS: The DA significantly improved ankle dorsiflexion during the mid-swing phase, making it more effective in correcting foot drop compared with the UD (DA: 2.28°, UD: 0.44°). Conversely, the UD was more effective in preventing knee flexion during the loading response (DA: 28.11°, UD: 26.72°). CONCLUSIONS: The DA improved ankle dorsiflexion during the swing phase significantly more than that with the UD in patients with hemiplegia. Compared with the DA, the UD more effectively prevented increased knee flexion during the loading response. The choice to prescribe these orthoses should consider individual patient characteristics.


Assuntos
Tornozelo , Órtoses do Pé , Humanos , Hemiplegia , Estudos Retrospectivos , Articulação do Tornozelo
9.
Sci Rep ; 14(1): 6944, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521821

RESUMO

Transient global amnesia (TGA) often involves precipitating events associated with changes in autonomic nervous system (ANS), and heart rate variability (HRV) reflects the ANS state. This study aimed to investigate HRV changes after TGA. A retrospective analysis of HRV included patients diagnosed with TGA between January 2015 and May 2020. The time and frequency domains of HRV were compared among three groups: early (< 1 week after TGA, n = 19), late (1-4 weeks after TGA, n = 38), and healthy control (HC, n = 19). The Pearson's correlation between time and time-domain HRV was also examined. The standard deviation of NN intervals (SDNN) (early, 47.2; late, 35.5; HC, 41.5; p = 0.033) and root mean square of successive RR interval differences (RMSSD) (early, 38.5; late, 21.3; HC, 31.0; p = 0.006) differed significantly among the three groups. Post-hoc analysis showed statistically significant differences only in the early and late groups in both SDNN (p = 0.032) and RMSSD (p = 0.006) values. However, the frequency domain with total power, low-frequency and high-frequency powers, and low-frequency/high-frequency ratio did not differ. SDNN (Pearson correlation coefficient =- 0.396, p = 0.002) and RMSSD (Pearson correlation coefficient =- 0.406, p = 0.002) were negatively correlated with time after TGA. Changes in HRV occurred over time after the onset of TGA, with the pattern showing an increase in the first week and then a decrease within 4 weeks.


Assuntos
Amnésia Global Transitória , Humanos , Frequência Cardíaca/fisiologia , Estudos Retrospectivos , Sistema Nervoso Autônomo
10.
Adv Mater ; : e2400977, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508776

RESUMO

Artificial intelligence (AI) is often considered a black box because it provides optimal answers without clear insight into its decision-making process. To address this black box problem, explainable artificial intelligence (XAI) has emerged, which provides an explanation and interpretation of its decisions, thereby promoting the trustworthiness of AI systems. Here, a memristive XAI hardware framework is presented. This framework incorporates three distinct types of memristors (Mott memristor, valence change memristor, and charge trap memristor), each responsible for performing three essential functions (perturbation, analog multiplication, and integration) required for the XAI hardware implementation. Three memristor arrays with high robustness are fabricated and the image recognition of 3 × 3 testing patterns and their explanation map generation are experimentally demonstrated. Then, a software-based extended system based on the characteristics of this hardware is built, simulating a large-scale image recognition task. The proposed system can perform the XAI operations with only 4.32% of the energy compared to conventional digital systems, enlightening its strong potential for the XAI accelerator.

11.
Front Neurol ; 15: 1330811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419706

RESUMO

Background: Intrathecal baclofen (ITB) therapy, a viable alternative for unsuitable candidates of conventional spasticity medications, is a preferred method of administration over the oral route. Owing to its enhanced bioavailability, ITB ensures a more effective delivery at the target site. Objective: There is a lack of conclusive evidence regarding the use of ITB treatment in managing ambulatory patients with spastic dystonia. Before ITB pump implantation, patients commonly undergo an ITB bolus injection trial to rule out potential adverse reactions and verify the therapeutic effects on hypertonic issues. In this report, we highlight a case of spastic dystonia, particularly focusing on an ambulatory patient who demonstrated significant improvement in both the modified Ashworth scale (MAS) score and gait pattern following the ITB injection trial. Case report: This case report outlines the medical history of a 67-year-old male diagnosed with left-side hemiplegia and spastic dystonia, resulting from his second episode of intracranial hemorrhage in the right thalamus. An ITB injection trial was initiated because the patient was not suitable for continued botulinum toxin injections and oral medications. This was due to the persistent occurrence of spastic dystonia in both the upper and lower extremities. The patient underwent a four-day ITB injection trial with progressively increasing doses, resulting in improved MAS scores and gait parameters, including cadence, step length, step time, stride length, and stride time were increased. Particularly, kinematic gait analysis demonstrates a substantial improvement of increased knee flexion in the swing phase in stiff knee gait pattern. These findings indicated a gradual reduction in spasticity-related symptoms, signifying the positive effect of the ITB injection trial. The patient eventually received an ITB pump implantation. Conclusion: In this post-stroke patient with spastic dystonia, ITB therapy has demonstrated effective and substantial management of spasticity, along with improvement in gait patterns.

12.
Seizure ; 117: 36-43, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38308907

RESUMO

PURPOSE: This study aimed to describe long-term treatment outcomes of treatment-naïve patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: A retrospective review was conducted of treatment-naïve patients with MTLE-HS who visited the Yonsei Epilepsy Clinic from April 2000 to April 2022 and were followed up for at least 2 years. Seizure freedom (SF) was defined as no seizures or auras only for >1 year, and complete SF was defined as no seizures including auras for >1 year. RESULTS: Eighty-four treatment-naïve patients with MTLE-HS with a median follow-up of 122 months were included. Except for one patient who underwent early surgical treatment, of the remaining 83 patients, 31 (37.3 %) achieved SF and remained in remission, 38 (45.8 %) had fluctuations in seizure control, and 14 (16.9 %) never achieved SF. Additionally, 18 (21.7 %) patients achieved complete SF and remained in remission, 42 (50.6 %) showed fluctuations, and 23 (27.7 %) never achieved complete SF. Fifty-three (63.9 %) patients achieved SF and 34 (41.0 %) achieved complete SF at their last visit. Older age at epilepsy onset, male sex, low pretreatment seizure density, history of central nervous system infection before age 5, absence of aura, and fewer antiseizure medications in the final regimen were associated with favorable outcome. Of the 84 patients, 11 (13.1 %) underwent temporal lobectomy. CONCLUSIONS: Medical treatment outcomes in treatment-naïve MTLE-HS were relatively better than previously reported outcomes in MTLE-HS, although frequent fluctuations in seizure control were observed.

14.
Sci Rep ; 14(1): 4006, 2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369569

RESUMO

Parthenium hysterophorus, a globally widespread weed, poses a significant threat to agricultural ecosystems due to its invasive nature. We investigated the chloroplast genome of P. hysterophorus in this study. Our analysis revealed that the chloroplast genome of P. hysterophorus spans a length of 151,881 base pairs (bp). It exhibits typical quadripartite structure commonly found in chloroplast genomes, including inverted repeat regions (IR) of 25,085 bp, a small single copy (SSC) region of 18,052 bp, and a large single copy (LSC) region of 83,588 bp. A total of 129 unique genes were identified in P. hysterophorus chloroplast genomes, including 85 protein-coding genes, 36 tRNAs, and eight rRNAs genes. Comparative analysis of the P. hysterophorus plastome with those of related species from the tribe Heliantheae revealed both conserved structures and intriguing variations. While many structural elements were shared among the species, we identified a rearrangement in the large single-copy region of P. hysterophorus. Moreover, our study highlighted notable gene divergence in several specific genes, namely matK, ndhF, clpP, rps16, ndhA, rps3, and ndhD. Phylogenetic analysis based on the 72 shared genes placed P. hysterophorus in a distinct clade alongside another species, P. argentatum. Additionally, the estimated divergence time between the Parthenium genus and Helianthus (sunflowers) was approximately 15.1 million years ago (Mya). These findings provide valuable insights into the evolutionary history and genetic relationships of P. hysterophorus, shedding light on its divergence and adaptation over time.


Assuntos
Asteraceae , Genoma de Cloroplastos , Filogenia , Plantas Daninhas/genética , 60715 , Ecossistema , Asteraceae/genética
15.
Adv Mater ; : e2309708, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251443

RESUMO

Insects can efficiently perform object motion detection via a specialized neural circuit, called an elementary motion detector (EMD). In contrast, conventional machine vision systems require significant computational resources for dynamic motion processing. Here, a fully memristive EMD (M-EMD) is presented that implements the Hassenstein-Reichardt (HR) correlator, a biological model of the EMD. The M-EMD consists of a simple Wye (Y) configuration, including a static resistor, a dynamic memristor, and a Mott memristor. The resistor and dynamic memristor introduce different signal delays, enabling spatio-temporal signal integration in the subsequent Mott memristor, resulting in a direction-selective response. In addition, a neuromorphic system is developed employing the M-EMDs to predict a lane-changing maneuver by vehicles on the road. The system achieved a high accuracy (> 87%) in predicting future lane-changing maneuvers on the Next Generation Simulation (NGSIM) dataset while reducing the computational cost by 92.9% compared to the conventional neuromorphic system without the M-EMD, suggesting its strong potential for edge-level computing.

16.
J Clin Sleep Med ; 20(1): 39-47, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163942

RESUMO

STUDY OBJECTIVES: We aimed to identify the relationship between duration of categorized catch-up sleep on free days (CUS) and measured body mass index (BMI) in adults using the data from the seventh Korean National Health and Nutrition Examination Survey (KNHANES VII), 2016. METHODS: CUS duration was classified as ≤ 0, > 0-1, > 1-2, and > 2 hours. Being overweight or obese was defined as having a BMI ≥ 25.0 kg/m2 or ≥ 30.0 kg/m2, respectively. RESULTS: Of 6,382 participants aged 19-80 years in the KNHANES VII survey of 2016, 201 and 583 participants were excluded because of shift-working and insufficient data, respectively. Of 5,598 participants, CUS was observed in 2,274 (44.9%) participants, of which 3,324 (55.1%), 1,043 (19.4%), 724 (14.7%), and 507 (10.8%) had CUS of ≤ 0, > 0-1, > 1-2, and > 2 hours, respectively; the prevalence of obesity was 5.6%, 5.6%, 4.8%, and 6.1%, respectively. The association between BMI and CUS duration showed a significant negative association in the CUS ≤ 0 hours group (beta [95% confidence interval], -0.394 [-0.646, -0.143], P = .002); however, other CUS groups did not show any significant association with BMI (CUS > 0-1 hours: -0.196 [-1.258, 0.865], P = .716; CUS > 1-2 hours, -0.542 [-1.625, 0.541], P = .325; CUS > 2 hours, -0.113 [-0.459, 0.233], P = .519). CONCLUSIONS: Our findings provide an understanding of the relationship between CUS and BMI and can serve as an instructive basis for the management of BMI. CITATION: Lee HJ, Cho S, Lee SH, Kim SJ, Kim KM, Chu MK. Catch-up sleep on free days and body mass index: results from the seventh Korea National Health and Nutrition Examination Survey, 2016. J Clin Sleep Med. 2024;20(1):39-47.


Assuntos
Obesidade , Sono , Adulto , Humanos , Índice de Massa Corporal , Inquéritos Nutricionais , Obesidade/epidemiologia , República da Coreia/epidemiologia
17.
Sensors (Basel) ; 24(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38203126

RESUMO

Synthetic data generation addresses the challenges of obtaining extensive empirical datasets, offering benefits such as cost-effectiveness, time efficiency, and robust model development. Nonetheless, synthetic data-generation methodologies still encounter significant difficulties, including a lack of standardized metrics for modeling different data types and comparing generated results. This study introduces PVS-GEN, an automated, general-purpose process for synthetic data generation and verification. The PVS-GEN method parameterizes time-series data with minimal human intervention and verifies model construction using a specific metric derived from extracted parameters. For complex data, the process iteratively segments the empirical dataset until an extracted parameter can reproduce synthetic data that reflects the empirical characteristics, irrespective of the sensor data type. Moreover, we introduce the PoR metric to quantify the quality of the generated data by evaluating its time-series characteristics. Consequently, the proposed method can automatically generate diverse time-series data that covers a wide range of sensor types. We compared PVS-GEN with existing synthetic data-generation methodologies, and PVS-GEN demonstrated a superior performance. It generated data with a similarity of up to 37.1% across multiple data types and by 19.6% on average using the proposed metric, irrespective of the data type.

18.
Materials (Basel) ; 17(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38204099

RESUMO

The surface hydrophilization of mixed plastic waste aggregates (MPAs) was conducted to improve the bond between an MPA and the surrounding cement matrix using two types of coating agents: a silicone amine resin and acrylic binders. The coating agents formed a physical bond with the MPAs, and the results of contact angle measurement also revealed that the surface of MPAs was hydrophilic. The workability of a mortar mix increased by up to 1.47 times with the surface hydrophilization of MPAs. Meanwhile, the compressive and flexural strengths of mortar mixes decreased by 29~43% and 72~86%, respectively, at 28 days with the surface hydrophilization of MPAs. Namely, the surface hydrophilization of MPAs was successively conducted, and the workability of mortar mixes was improved accordingly, but the compressive and flexural strengths of mortar mixes decreased as the physical bond was partially separated from not only the MPA but also the surrounding cement matrix and the surface friction was decreased.

19.
Biomed Pharmacother ; 171: 116126, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219386

RESUMO

The main cause of inflammatory bowel disease (IBD) is abnormal intestinal permeability due to the disruption of the tight junction of the intestinal barrier through a pathogen-mediated inflammatory mechanism and an imbalance of the gut microbiota. This study aimed to evaluate whether 2-ketoglutaric acid alleviated permeability dysfunction with tight junction localization, activated the transforming growth factor beta-activated kinase 1 (TAK1) inflammation pathway, and regulated the homeostasis of the intestinal microbiome in vitro and in vivo IBD model. Our findings revealed that 2-ketoglutaric acid significantly suppressed abnormal intestinal permeability, delocalization of tight junction proteins from the intestinal cell, expression of inflammatory cytokines, such as TNF-α, both in vitro and in vivo. 2-Ketoglutaric acid was found to directly bind to TAK1 and inhibit the TNF receptor-associated factor 6 (TRAF6)-TAK1 interaction, which is related to the activation of nuclear factor kappa B (NF-κB) pathways, thereby regulating the expression of mitogen-activated protein kinase. Dietary 2-ketoglutaric acid also alleviated gut microbiota dysbiosis and IBD symptoms, as demonstrated by improvements in the intestine length and the abundance of Ligilactobacillus, Coriobacteriaceae_UCG_002, and Ruminococcaceae_unclassified in mice with colitis. This study indicated that 2-ketoglutaric acid binds to TAK1 for activity inhibition which is related to the NF-κB pathway and alleviates abnormal permeability by regulating tight junction localization and gut microbiome homeostasis. Therefore, 2-ketoglutaric acid is an effective nutraceutical agent and prebiotic for the treatment of IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Camundongos , Animais , NF-kappa B/metabolismo , Ácidos Cetoglutáricos/farmacologia , Mucosa Intestinal , Prebióticos , Quinase de Cadeia Leve de Miosina/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Colite/metabolismo , Sulfato de Dextrana/farmacologia , Junções Íntimas , Camundongos Endogâmicos C57BL
20.
Sci Rep ; 14(1): 1214, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216610

RESUMO

Due to global climate change, crops are certainly confronted with a lot of abiotic and biotic stress factors during their growth that cause a serious threat to their development and overall productivity. Among different abiotic stresses, salt and drought are considered the most devastating stressors with serious impact on crop's yield stability. Here, the current study aimed to elucidate how melatonin works in regulating plant biomass, oxidative stress, antioxidant defense system, as well as the expression of genes related to salt and drought stress in rice plants. Eight groups of rice plants (3 replicates, 5 plants each) underwent varied treatments: control, melatonin, salt, drought, salt + drought, salt + melatonin, drought + melatonin, and salt + drought + melatonin. Melatonin (100 µM) was alternately applied a week before stress exposure; salt stress received 100 mM NaCl every 3 days for 3 weeks, and drought stress involved 10% PEG. Young leaves were randomly sampled from each group. The results showed that melatonin treatment markedly reduces salt and drought stress damage by promoting root, shoot length, fresh and dry weight, increasing chlorophyll contents, and inhibiting excessive production of oxidative stress markers. Salt and drought stress significantly decreased the water balance, and damaged cell membrane by reducing relative water contents and increasing electrolyte leakage. However, melatonin treated rice plants showed high relative water contents and low electrolyte leakage. Under salt and drought stress conditions, exogenous application of melatonin boosted the expression level of salt and drought stress responsive genes like OsSOS, OsNHX, OsHSF and OsDREB in rice plants. Taken together, our results reveal that melatonin treatment significantly increases salt and drought tolerance of rice plants, by increasing plant biomass, suppressing ROS accumulation, elevating antioxidants defense efficiency, and up-regulating the expression of salt and drought stress responsive genes.


Assuntos
Melatonina , Oryza , Melatonina/farmacologia , Melatonina/metabolismo , Secas , Oryza/metabolismo , Resistência à Seca , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Fisiológico/genética , Eletrólitos/metabolismo , Água/metabolismo
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