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1.
J Stroke Cerebrovasc Dis ; : 107712, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599473

RESUMO

BACKGROUND: Previous studies have indicated the potential occurrence of alexithymia among stroke patients, yet the prevalence of alexithymia in this population remains disparate across different investigations without a synthesized overview. AIM: To systematically evaluate the prevalence and characteristics of alexithymia in stroke patients. METHODS: A systematic review and meta-analysis was conducted following the PRISMA guidelines. PubMed, Embase, Web of Science, The Cochrane Library, CINAHL, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Biomedical Database, and Weipu Database (VIP) were searched from inception to December 31,2022, two independent researchers extracted data and evaluated article quality. RESULTS: Seventeen studies were included, reporting on the prevalence of alexithymia or Toronto Alexithymia Scale-20 (TAS-20) scores among stroke patients. The pooled prevalence was found to be 35.0% (95%CI= 23.0-47.0%; I2 =97.5%), and the total scores (TS) of TAS-20 was 59.90 (95% CI=56.34-63.47; I2 =100.0%). Subgroup analysis revealed significant variation in TAS-20 scores across different geographical regions. Specifically, the total TAS-20 score in Chinese stroke patients (62.95, 95%CI=58.75-67.14; I2=100%) was higher compared to non-Chinese stroke patients (52.58, 95%CI=49.12-56.04; I2 = 99.0%). CONCLUSIONS: The prevalence of alexithymia is high among stroke patients, with TAS-20 scores surpassing those observed in patients with certain other medical conditions. This underscores the importance of addressing alexithymia in stroke patients promptly through assessment and intervention to mitigate negative emotional consequences and enhance overall quality of life. Future research could explore the influence of demographic factors such as age and sex on alexithymia in stroke patients, enabling a more comprehensive understanding of alexithymia.

2.
Postgrad Med ; : 1-14, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38635593

RESUMO

Gallbladder cancer is a common type of biliary tract tumor. Optimal management for early stage cases typically involves radical excision as the primary treatment modality. Various surgical techniques, including laparoscopic, robotic, and navigational surgery, have demonstrated favorable clinical outcomes in radical gallbladder excision. Unfortunately, most patients are ineligible for surgical intervention because of the advanced stage of the disease upon diagnosis. Consequently, non-surgical interventions, such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, have become the mainstay of treatment for patients in advanced stages. This review focuses on elucidating various surgical techniques as well as advancements in immunotherapy and targeted therapy in the context of recent advancements in gallbladder cancer research.

3.
BMC Surg ; 24(1): 117, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643065

RESUMO

BACKGROUND: This study investigated the clinical application of the indocyanine green (ICG) fluorescence navigation technique in bile duct identification during laparoscopic common bile duct exploration (LCBDE) for complex hepatolithiasis. METHODS: Eighty patients with complex hepatolithiasis were admitted to our department between January 2022 and June 2023 and randomly divided into control and observation groups. The control group underwent conventional LCBDE, while the observation group underwent LCBDE guided by ICG fluorescence. RESULTS: Intraoperatively, the observation group had shorter operation and search times for the common bile duct (CBD), as well as reduced intraoperative blood loss and fewer complications, such as conversion to laparotomy and various injuries (gastroduodenal, colon, pancreatic, and vascular) than the control group, with statistical significance (P < 0.05). Postoperatively, the observation group had lower rates of postoperative bile leakage, abdominal infection, postoperative hemorrhage, and residual stone than the control group. Additionally, the observation group demonstrated significantly shorter times for resuming flatus, removal of the abdominal drainage tube, and hospitalization than the control group, with statistical significance (P < 0.05). CONCLUSION: ICG fluorescence navigation technology effectively visualizes the bile duct, improves its identification rate, shortens the operation time, prevents biliary tract injury, and reduces the occurrence of complications.


Assuntos
Coledocolitíase , Laparoscopia , Litíase , Hepatopatias , Humanos , Verde de Indocianina , Coledocolitíase/cirurgia , Hepatopatias/cirurgia , Litíase/cirurgia , Estudos Retrospectivos , Laparoscopia/métodos , Ducto Colédoco/cirurgia , Tempo de Internação
4.
Front Oncol ; 14: 1280607, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646429

RESUMO

Objective: There is still controversy about whether cervical lymph node dissection should be performed in surgical treatment of PTC. Based on the data of thyroid cancer patients from Liaocheng People's Hospital from 2015 to 2018, this study focused on appropriate indications for cervical lymph node dissection surgery. Methods: The clinical and pathological data of patients with initial treatment of PTC in thyroid surgery department from 2015 to 2018 were collected. In all cases, 1001 patients underwent total thyroidectomy + central lymph node dissection, and 1107 patients underwent total thyroidectomy + central + cervical lymph node dissection. Results: The average metastasis rate of all cases was 57.23%, and even the metastasis rate of PTMC was as high as 48.97%. The total metastasis rate of central and lateral cervical lymph nodes was 74.44%, and the cervical lymph nodes were present in 49.32% of the metastatic cases. In 55.56% of the cases, the tumor diameter was more than 1 cm, and the metastasis rate of cervical lateral area was 56%. With the increase of tumor diameter, the cervical metastasis rate increased from 22.54% to 73.33%. Conclusion: The metastasis rate of PTC is more than 50%, and nearly half of them have cervical metastasis, especially in patients with high risk factors. We observed that PTC 1 cm or greater has significant rates of metastasis.

5.
Comput Biol Med ; 174: 108392, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38608321

RESUMO

Proteins must be sorted to specific subcellular compartments to perform their functions. Abnormal protein subcellular localizations are related to many diseases. Although many efforts have been made in predicting protein subcellular localization from various static information, including sequences, structures and interactions, such static information cannot predict protein mis-localization events in diseases. On the contrary, the IHC (immunohistochemistry) images, which have been widely applied in clinical diagnosis, contains information that can be used to find protein mis-localization events in disease states. In this study, we create the Vislocas method, which is capable of finding mis-localized proteins from IHC images as markers of cancer subtypes. By combining CNNs and vision transformer encoders, Vislocas can automatically extract image features at both global and local level. Vislocas can be trained with full-sized IHC images from scratch. It is the first attempt to create an end-to-end IHC image-based protein subcellular location predictor. Vislocas achieved comparable or better performances than state-of-the-art methods. We applied Vislocas to find significant protein mis-localization events in different subtypes of glioma, melanoma and skin cancer. The mis-localized proteins, which were found purely from IHC images by Vislocas, are in consistency with clinical or experimental results in literatures. All codes of Vislocas have been deposited in a Github repository (https://github.com/JingwenWen99/Vislocas). All datasets of Vislocas have been deposited in Zenodo (https://zenodo.org/records/10632698).

6.
J Cardiol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583664

RESUMO

The tricuspid valve is known as "the forgotten valve". Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease. TR is often late in the course of the disease when it becomes symptomatic, often being a marker of late-stage chronic heart failure with a poor prognosis and high mortality rate at long-term follow-up. Despite the clear correlation between TR and mortality, most TR patients are under-treated. Neither pharmacologic nor surgical treatment demonstrates a significant survival benefit. Isolated tricuspid valve surgery has the highest mortality rate of all valve surgeries. Therefore, there is an urgent clinical need for minimally invasive therapies to meet the needs of patients with TR. In recent years, a variety of transcatheter tricuspid valve interventions representing less invasive alternatives to surgery have shown promising results, which bring hope to patients with severe TR. The purpose of this review is to provide a complete and updated overview on current transcatheter tricuspid valve interventions and clinical evidence.

8.
Chembiochem ; : e202300821, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564329

RESUMO

Bile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are needed to profile gut microbiota-associated enzymes such as BSH. Here, we develop a panel of BSH activity-based probes (ABPs) to determine how changes in diurnal rhythmicity of gut microbiota-associated metabolism affects BSH activity and substrate preference. This panel of covalent probes enables determination of BSH activity and substrate specificity from multiple gut anerobic bacteria derived from the human and mouse gut microbiome. We found that both gut microbiota-associated BSH activity and substrate preference is rhythmic, likely due to feeding patterns of the mice. These results indicate that this ABP-based approach can be used to profile changes in BSH activity in physiological and disease states that are regulated by circadian rhythms.

9.
bioRxiv ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38617281

RESUMO

The gut microbiome possesses numerous biochemical enzymes that biosynthesize metabolites that impact human health. Bile acids comprise a diverse collection of metabolites that have important roles in metabolism and immunity. The gut microbiota-associated enzyme that is responsible for the gateway reaction in bile acid metabolism is bile salt hydrolase (BSH), which controls the host's overall bile acid pool. Despite the critical role of these enzymes, the ability to profile their activities and substrate preferences remains challenging due to the complexity of the gut microbiota, whose metaproteome includes an immense diversity of protein classes. Using a systems biochemistry approach employing activity-based probes, we have identified gut microbiota-associated BSHs that exhibit distinct substrate preferences, revealing that different microbes contribute to the diversity of the host bile acid pool. We envision that this chemoproteomic approach will reveal how secondary bile acid metabolism controlled by BSHs contributes to the etiology of various inflammatory diseases.

10.
Anal Chim Acta ; 1304: 342576, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38637043

RESUMO

BACKGROUND: Small endosome-derived lipid nanovesicles (30-200 nm) are actively secreted by living cells and serve as pivotal biomarkers for early cancer diagnosis. However, the study of extracellular vesicles (EVs) requires isolation and purification from various body fluids. Although traditional EVs isolation and detection technologies are mature, they usually require large amount of sample, consumes long-time, and have relatively low-throughput. How to efficiently isolate, purify and detect these structurally specific EVs from body fluids with high-throughput remains a great challenge in in vitro diagnostics and clinical research. RESULTS: Herein, we suggest a nanosized microfluidic device for efficient and economical EVs filtration based on an alumina nanochannel array membrane. We evaluated the filtration device performance of alumina membranes with different diameters and found that an optimized chamber array with a hydrophilic-treated channel diameter of 90 nm could realize a filtration efficiency of up to 82% without any assistance from chemical or physical separation methods. Importantly, by integrating meticulously designed multichannel microfluidic biochips, EVs can be captured in-situ and monitored by antibody barcode biochip. The proposed filtration chip together with the high-throughput detection chip were capable of filtration of a few tens of µL samples and recognition of different phonotypes. The practical filtration and detection of EVs from clinical samples demonstrated the high performance of the device. SIGNIFICANT: Overall, this work provides a cost-effective, highly efficient and automated EVs filtration chip and detection dual-function integrated chip platform, which can directly separate EVs from serum or cerebrospinal fluid with an efficiency of 82% and conduct in-situ detection. This small fluidic device can provide a powerful tool for highly efficient identifying and analyzing EVs, presenting great application potential in clinical detection.


Assuntos
Vesículas Extracelulares , Microfluídica , Espaço Extracelular , Anticorpos , Biomarcadores Tumorais
11.
Precis Clin Med ; 7(1): pbae003, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38495337

RESUMO

Background: Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus (T2DM), can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian decoction (GQD). This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD. Methods: We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM. During the 12-week intervention, anthropometric measurements and diabetic traits were recorded every 4 weeks. Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing, liquid chromatography-mass spectrometry, and Bio-Plex panels. Results: Anti-diabetic effects were observed in the GQD group in the human trial. Specifically, glycated hemoglobin, fasting plasma glucose, and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group. Additionally, Faecalibacterium was significantly enriched in the GQD group, and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group. Moreover, Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin, fasting plasma glucose, and pro-inflammatory cytokines. Finally, the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzii (DSMZ 17677) in T2DM mouse model. Conclusions: GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state. Trial registration: Registry No. ChiCTR-IOR-15006626.

12.
ACS Appl Mater Interfaces ; 16(12): 15133-15142, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38488729

RESUMO

Dynamic control of ultralong organic room-temperature phosphorescence (UORTP) is a charming target. Herein, we report a stimuli-responsive phosphorescence unit 7H-indolo[2,3-c]quinoline (NBCz) and its derivatives (PCBNBCz, FSO2NBCz, and N2BCzSO2NBCz) that show photo- and oxygen- synergistically induced afterglow activation and afterglow color change in the PMMA film. PCBNBCz and FSO2NBCz feature a donor-acceptor (D-A) structure, and N2BCzSO2NBCz features acceptor-bridged two different phosphorescence units (NBCz and N2BCz). The photoactivated UORTP of PCBNBCz and FSO2NBCz arises from the photoinduced consumption of oxygen in the PMMA film. It is clear that the phosphorescence unit NBCz contributes to subsequent photoinduced UORTP color change because the NBCz-doped PMMA film shows the same UORTP color change process. ESR and HRMS measurements confirmed that oxidation of NBCz occurs at the nitrogen atom of the quinoline ring via photogenerated superoxide radicals, which results in the UORTP color change. TDDFT calculations proved that after oxidation of NBCz, the T1 energy level declines significantly. Furthermore, photocontrolled selective expression of phosphorescence units is achieved in the case of N2BCzSO2NBCz. After further UV irradiation, oxidation of NBCz happened, and the oxidized form N2BCzSO2NBCz-O emitted the intrinsic orange UORTP of NBCz-O selectively and screened the intrinsic yellowish-green UORTP of N2BCz. Finally, multilevel photolithography can be demonstrated based on the photoactivated UORTP and the photoinduced UORTP color change. This work may give a deep insight into organic phosphorescence and pave a simple way for the development of stimulus-responsive smart UORTP materials.

14.
J Thorac Dis ; 16(2): 1171-1179, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505028

RESUMO

Background: The diagnosis, treatment, and prognosis of early postoperative constrictive pericarditis (EPCP) have not been discussed in depth. The objective of this study was to devise and propose a management strategy for EPCP. Methods: In this study, constrictive pericarditis (CP) within 6 months after cardiac surgery was defined as EPCP, and patients were divided into two groups based on intraoperative findings: a parietal thickening group and a visceral thickening group. Results: A total of 20 patients were included in this study, and the incidence rate of recurrent pericardiectomy was 0.32% among all patients undergoing cardiovascular surgery. EPCP after valve surgery occurred in 85.0% of patients. Pleural effusion was the most common preoperative symptom, occurring in 90% of patients. Pericardial thickening occurred in the visceral layer in seven cases and in the parietal layer in 13 cases. There were no differences in comorbidities, C-reactive protein (CRP) level, or erythrocyte sedimentation rate (ESR) between the two groups. Most patients with visceral thickening (83.3%) needed cardiopulmonary bypass (CPB) assistance during surgery and had a longer hospital stay than those with parietal thickening (52.8±21.8 vs. 34.9±13.8 days, P=0.049). Central venous pressure (CVP) was decreased in all patients after pericardiectomy (24.9±6.96 vs. 8.9±2.92 cmH2O, P<0.001), and the cardiac function improved significantly in patients with parietal thickening [New York Heart Association (NYHA) grade ≥ III accounted for 28.6% of patients]. The long-term survival rate of patients with parietal thickening was 92.3% and that of patients with visceral thickening was 57.1%, and there was no significant difference between them (P=0.056). Conclusions: Recurrent episodes of chest tightness, pleural effusion, and elevated CVP within 6 months after cardiac surgery should be considered highly suggestive of EPCP. There are few points of difference between pericarditis with thickening of the parietal and visceral layers. After failure of conservative medical treatment, pericardiectomy results in significant improvements in cardiac function and quality of life, especially in patients with thickening of the parietal layer.

15.
Front Microbiol ; 15: 1304985, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550872

RESUMO

Soil nitrogen (N) availability is one of the limiting factors of crop productivity, and it is strongly influenced by global change and agricultural management practices. However, very few studies have assessed how the winter drought affected soil N availability during the subsequent growing season under chemical fertilization. We conducted a field investigation involving snow removal to simulate winter drought conditions in a Mollisol cropland in Northeast China as part of a 6-year fertilization experiment, and we examined soil physicochemical properties, microbial characteristics, and N availability. Our results demonstrated that chemical fertilization significantly increased soil ammonium and total N availability by 42.9 and 90.3%, respectively; a combined winter drought and fertilization treatment exhibited the highest soil N availability at the end of the growing season. As the growing season continued, the variation in soil N availability was explained more by fertilization than by winter drought. The Mantel test further indicated that soil Olsen-P content and microbial carbon use efficiency (CUE) were significantly related to soil ammonium availability. A microbial community structure explained the largest fraction of the variation in soil nitrate availability. Microbial CUE showed the strongest correlation with soil N availability, followed by soil available C:P and bacteria:fungi ratios under winter drought and chemical fertilization conditions. Overall, we clarified that, despite the weak effect of the winter drought on soil N availability, it cannot be ignored. Our study also identified the important role of soil microorganisms in soil N transformations, even in seasonally snow-covered northern croplands.

16.
J Tissue Viability ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38553354

RESUMO

BACKGROUND: Pressure injuries (PIs) are one of the leading potentially preventable hospital-acquired complications associated with prolonged hospital length, poor quality of life and financial burden. The relationship between body mass index (BMI) and PIs occurrence is controversial. OBJECTIVE: The aim of this study was to further examine relationships between BMI and PIs occurrence in hospitalized patients. DESIGN: A multi-center prospective study. SETTING: 39 hospitals located in northwest China from April 2021 to July 2023. PARTICIPANTS: 175,960 hospitalized patients aged over 18 years were enrolled, and 170,800 patients were included in the final analysis. METHODS: BMI and clinical characteristics were assessed at baseline. PIs assessment were performed by trained nurses, with data recorded for the presence, the location and stage of each PI. For staging PIs, the National Pressure Ulcer Advisory Panel(NPUAP) staging system were used. The multivariate logistic regressions analysis and restricted cubic splines (RCS) models were used to explore associations between BMI and PIs, adjusting for potential confounders. RESULTS: Of 175,960 participants, 5160 were excluded from analyses. The multivariate logistic regression model identified a positive relationship between under-weight BMI and risk of PIs occurrence (OR = 1.60, 95% CI:1.18-2.17). We also found U shaped association between BMI and PIs occurrence (non-linear P < 0.001). BMI less than 23 kg/m2 significantly increased risk of PIs, and there was a tendency to increase risk of PIs at BMI higher than 30 kg/m2. We stratified participants by sex to further investigate their association and found the risk of PIs increases substantially in women at BMI below 17 kg/m2 and in men at BMI below 23 kg/m2. CONCLUSIONS: The present study indicated that there was an approximate U shaped relationship between BMI and PIs occurrence, and this association was potentially different between men and women.

17.
Opt Lett ; 49(6): 1508-1511, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489437

RESUMO

Spontaneous infrared radiation dissipation is a critical factor in facilitating object cooling, which influences the thermal stability and stealth efficacy of infrared stealth devices. Furthermore, the compatibility between efficient visible, infrared, and radar stealth is challenging due to different camouflage principles in different bands. This Letter presents a five-layer etched film structure to achieve multispectral stealth, and the utilization of the high-quality ultrathin silver films enables highly efficient infrared selective emission. This etched film structure with few layers demonstrates potential applications in diverse domains, including multi-band anti-detection and multispectral manipulation.

18.
Nat Methods ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532015

RESUMO

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

19.
Nat Commun ; 15(1): 2766, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553465

RESUMO

Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or instead utilize existing extracellular matrix microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3-dimensional migration, few recapitulate these natural migration paths. Here, we develop a biopolymer-based bicontinuous hydrogel system that comprises a covalent hydrogel of enzymatically crosslinked gelatin and a physical hydrogel of guest and host moieties bonded to hyaluronic acid. Bicontinuous hydrogels form through controlled solution immiscibility, and their continuous subdomains and high micro-interfacial surface area enable rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior is mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which is shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a design that leverages important local interfaces to guide rapid cell migration.


Assuntos
Matriz Extracelular , Hidrogéis , Hidrogéis/química , Movimento Celular , Matriz Extracelular/metabolismo , Esferoides Celulares , Biopolímeros/metabolismo
20.
Int Immunopharmacol ; 130: 111738, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38428149

RESUMO

BACKGROUND: Neuroinflammation, a critical component of the secondary injury cascade post-spinal cord injury, involves the activation of pro-inflammatory cells and release of inflammatory mediators. Resolution of neuroinflammation is closely linked to cellular autophagy. This study investigates the potential of Fisetin, a natural anti-inflammatory compound, to ameliorate neuroinflammation and confer spinal cord injury protection through the regulation of autophagy in pro-inflammatory cells. METHODS: Utilizing a rat T10 spinal cord injury model with distinct treatment groups (Sham, Fisetin-treated, and Fisetin combined with autophagy inhibitor), alongside in vitro models involving lipopolysaccharide (LPS)-stimulated microglial cell activation and co-culture with neurons, we employed techniques such as transcriptomic sequencing, histological assessments (immunofluorescence staining, etc.), molecular analyses (PCR, WB, ELISA, etc.), and behavioral evaluations to discern differences in neuroinflammation, autophagy, neuronal apoptosis, and neurological function recovery. RESULTS: Fisetin significantly augmented autophagic activity in injured spinal cord tissue, crucially contributing to neurological function recovery in spinal cord-injured rats. Fisetin's autophagy-dependent effects were associated with a reduction in neuronal apoptosis at the injury site. The treatment reduced the population of CD68+ and iNOS+ cells, coupled with decreased pro-inflammatory cytokines IL-6 and TNF-α levels, through autophagy-dependent pathways. Fisetin pre-treatment attenuated LPS-induced pro-inflammatory polarization of microglial cells, with this protective effect partially blocked by autophagy inhibition. Fisetin-induced autophagy in the injured spinal cord and pro-inflammatory microglial cells was associated with significant activation of AMPK and inhibition of mTOR. CONCLUSION: Fisetin orchestrates enhanced autophagy in pro-inflammatory microglial cells through the AMPK-mTOR signaling pathway, thereby mitigating neuroinflammation and reducing the apoptotic effects of neuroinflammation on neurons. This mechanistic insight significantly contributes to the protection and recovery of neurological function following spinal cord injury, underscoring the vital nature of Fisetin as a potential therapeutic agent.


Assuntos
Flavonóis , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal , Ratos , Animais , Lipopolissacarídeos/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Inflamação/metabolismo , Traumatismos da Medula Espinal/complicações , Serina-Treonina Quinases TOR/metabolismo , Medula Espinal/patologia , Microglia , Autofagia
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