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1.
Diabetes Obes Metab ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118216

RESUMO

AIM: To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD. RESULTS: Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all ptrend <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk. CONCLUSIONS: This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD.

3.
Environ Pollut ; 360: 124716, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39142431

RESUMO

In this study, the concentration of inorganic ions (SO42-, NH4+, NO3- and NO2-) and morphological characteristics of condensable particulate matter (CPM) were investigated to elucidate the formation mechanism of inorganic CPM from ultra-low emission coal-fired power plants. The concentration of inorganic ions increased with the increase of H2O content and concentration of inorganic gaseous contaminants (SO2, NOX and NH3), and decrease of condensation temperature, indicating the enhancement of heterogenous reaction in the saturated flue gas. Furthermore, NOX and SO2 could undergo redox reactions, leading to an elevation in the concentration of SO42- and NO3-. Additionally, the introduction of NH3 resulted in increased concentrations of SO42-, NO3-, and NO2-, highlighting the significant role of NH3 neutralization in CPM nucleation. The condensation of SO3/sulfuric acid aerosols was enhanced under saturation conditions, and SO2 and SO3/sulfuric acid aerosols could contribute synergistically to the formation of SO42-. Moreover, morphological analysis revealed the presence of both well-aggregated solid CPM and dispersed liquid CPM, confirming the formation of inorganic CPM during fast condensation. Furthermore, the detected CPM were composed of S and O, which identified the significant role of sulfates in the inorganic CPM. These findings provide valuable insights for the control of inorganic CPM in flue gas systems.

4.
Placenta ; 155: 32-41, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39121585

RESUMO

INTRODUCTION: Preeclampsia is a pregnancy-specific disorder characterized by de novo development of hypertension and proteinuria over 20 weeks gestation that has been associated with the dysfunction of trophoblasts. Current evidence suggests that syncytin-1 plays an important role in the non-fusogenic biological activity of trophoblasts, except for specific fusogenic function. However, the underlying mechanism remains unclear. METHODS: The expression and location of syncytin-1 in normal and the late-onset preeclampsia placentas were detected by quantitative real-time PCR, western blotting and immunofluorescence. Morphological and apoptosis analysis were processed in placentas. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Real-time quantitative PCR and immunoblotting were used to calculate syncytin-1 levels in the trophoblast cells before and after syncytin-1 knockdown or overexpression. CCK-8 assay was used to detect the cell viability. TUNEL staining and immunoblotting were processed in trophoblast cells. Transwell assays and wound healing assays were utilize to assess the invasion and migration of trophoblastic cells. Conditional knockout of syncytin-a mouse model was conducted to present the change of placentas in vivo. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Western blotting was used to identify the key proteins of PI3K/Akt pathways and invasion-related proteins in trophoblast cells. RESULTS AND DISCUSSION: Here, reduced syncytin-1 was identified in the late-onset preeclampsia placentas. Reduced syncytin-1 may attenuates the EMT process by promoting apoptosis, inhibiting proliferation and invasion by suppressed PI3K/Akt pathway in trophoblast cells. Our findings provide novel insights into the non-fusogenic biological function of reduced syncytin-1 that may be involves in the pathogenesis of preeclampsia.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39067514

RESUMO

OBJECTIVES: To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in hematopoietic stem cell transplantation (HSCT) patients and analyze POS plasma concentrations. METHODS: A single-arm trial was designed with a historical cohort as control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences (CAMS) from December 2020 to May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. RESULTS: The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81% [95% CI, 0.09%-5.50%] versus 7.69% [95% CI, 4.60%-10.78%]; P = 0.044). Adverse events were comparable between the groups, with liver changes in 33/144 (22.92%) versus 84/287 (29.27%) (P = 0.162), and renal injuries in 15/144 (10.41%) versus 37/287 (12.89%) (P = 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22post-administration were 930.97 ng/ml, 1143.97 ng/ml, 1569.8 ng/ml, and 1652.57 ng/ml, respectively. CONCLUSION: Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentration in HSCT patients stabilized by day 15 of medication.

6.
World J Orthop ; 15(7): 642-649, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39070933

RESUMO

BACKGROUND: Tibial avulsion fractures of the posterior cruciate ligament (PCL) are challenging to treat and compromise knee stability and function. Traditional open surgery often requires extensive soft tissue dissection, which may increase the risk of morbidity. In response to these concerns, arthroscopic techniques have been evolving. The aim of this study was to introduce a modified arthroscopic technique utilizing an M-shaped suture fixation method for the treatment of tibial avulsion fractures of the PCL and to evaluate its outcomes through a case series. AIM: To evaluate the effects of arthroscopic M-shaped suture fixation on treating tibia avulsion fractures of the PCL. METHODS: We developed a modified arthroscopic M-shaped suture fixation technique for tibia avulsion fractures of the PCL. This case series included 18 patients who underwent the procedure between January 2021 and December 2022. The patients were assessed for range of motion (ROM), Lysholm score and International knee documentation committee (IKDC) score. Postoperative complications were also recorded. RESULTS: The patients were followed for a mean of 13.83 ± 2.33 months. All patients showed radiographic union. At the final follow-up, all patients had full ROM and a negative posterior drawer test. The mean Lysholm score significantly improved from 45.28 ± 8.92 preoperatively to 91.83 ± 4.18 at the final follow-up (P < 0.001), and the mean IKDC score improved from 41.98 ± 6.06 preoperatively to 90.89 ± 5.32 at the final follow-up (P < 0.001). CONCLUSION: The modified arthroscopic M-shaped suture fixation technique is a reliable and effective treatment for tibia avulsion fractures of the PCL, with excellent fracture healing and functional recovery.

11.
Postgrad Med ; 136(5): 551-561, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38912825

RESUMO

OBJECTIVE: The aim of this study is to examine the perception, willingness to engage, and demand of community residents regarding the 'internet + nursing service' in a designated pilot area, aiming to offer insights for the widespread adoption of the 'internet + nursing service' throughout China. METHODS: A survey pertaining to the 'internet + nursing service' was conducted from March to April 2022. The study specifically targeted residents within two sub-districts of a city in the Jiangsu province. The sampling technique employed in this study was stratified random sampling. RESULTS: Out of a total of 400 community residents selected from two sub-districts in this region, 378 provided valid responses, resulting in an effective rate of 94.5%. Within the study cohort, 80 participants (21.16%) demonstrated familiarity with the concept of 'internet + nursing service.' Additionally, 231 participants (61.11%) conveyed their willingness to adopt such services. Regarding service preferences, the primary demands were for health guidance, vital sign monitoring, and basic care. Challenges in implementing the service were attributed to concerns related to medical risks, personal safety for both nurses and patients, and potential breaches of privacy. CONCLUSIONS: Residents in the pilot area exhibited a moderate awareness of the 'internet + nursing service,' with a relatively high willingness to embrace the program. There is a need for further refinement of pertinent laws, widespread dissemination of policies, and enhancements in the quality of nursing services. These measures aim to ensure that a greater number of community residents can avail themselves of improved home-based nursing services.


Assuntos
Internet , Humanos , China , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Inquéritos e Questionários , Serviços de Assistência Domiciliar/organização & administração
12.
Asian J Androl ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38748865

RESUMO

ABSTRACT: Systematic prostate biopsy has limitations, such as overdiagnosis of clinically insignificant prostate cancer and underdiagnosis of clinically significant prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy, a promising alternative, might improve diagnostic accuracy. To compare the cancer detection rates of systematic biopsy and combined biopsy (systematic biopsy plus MRI-targeted biopsy) in Asian men, we conducted a retrospective cohort study of men who underwent either systematic biopsy or combined biopsy at two medical centers (Queen Mary Hospital and Tung Wah Hospital, Hong Kong, China) from July 2015 to December 2022. Descriptive statistics were calculated, and univariate and multivariate logistic regression analyses were performed. The primary and secondary outcomes were prostate cancer and clinically significant prostate cancer. A total of 1391 participants were enrolled. The overall prostate cancer detection rates did not significantly differ between the two groups (36.3% vs 36.6%, odds ratio [OR] = 1.01, 95% confidence interval [CI]: 0.81-1.26, P = 0.92). However, combined biopsy showed a significant advantage in detecting clinically significant prostate cancer (Gleason score ≥ 3+4) in patients with a total serum prostate-specific antigen (tPSA) concentration of 2-10 ng ml-1 (systematic vs combined: 11.9% vs 17.5%, OR = 1.58, 95% CI: 1.08-2.31, P = 0.02). Specifically, in the transperineal biopsy subgroup, combined biopsy significantly outperformed systematic biopsy in the detection of clinically significant prostate cancer (systematic vs combined: 12.6% vs 24.0%, OR = 2.19, 95% CI: 1.21-3.97, P = 0.01). These findings suggest that in patients with a tPSA concentration of 2-10 ng ml-1, MRI-targeted biopsy may be of greater predictive value than systematic biopsy in the detection of clinically significant prostate cancer.

13.
Bioengineering (Basel) ; 11(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38790312

RESUMO

BACKGROUND AND AIMS: Accurate recognition of endoscopic instruments facilitates quantitative evaluation and quality control of endoscopic procedures. However, no relevant research has been reported. In this study, we aimed to develop a computer-assisted system, EndoAdd, for automated endoscopic surgical video analysis based on our dataset of endoscopic instrument images. METHODS: Large training and validation datasets containing 45,143 images of 10 different endoscopic instruments and a test dataset of 18,375 images collected from several medical centers were used in this research. Annotated image frames were used to train the state-of-the-art object detection model, YOLO-v5, to identify the instruments. Based on the frame-level prediction results, we further developed a hidden Markov model to perform video analysis and generate heatmaps to summarize the videos. RESULTS: EndoAdd achieved high accuracy (>97%) on the test dataset for all 10 endoscopic instrument types. The mean average accuracy, precision, recall, and F1-score were 99.1%, 92.0%, 88.8%, and 89.3%, respectively. The area under the curve values exceeded 0.94 for all instrument types. Heatmaps of endoscopic procedures were generated for both retrospective and real-time analyses. CONCLUSIONS: We successfully developed an automated endoscopic video analysis system, EndoAdd, which supports retrospective assessment and real-time monitoring. It can be used for data analysis and quality control of endoscopic procedures in clinical practice.

14.
Medicine (Baltimore) ; 103(16): e37816, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640275

RESUMO

To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (n = 382) and observation group (n = 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (P > .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (P < .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (P < .05). The negative emotion score of the observation group was significantly lower than that of the control group (P < .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (P < .05). The bladder function was significantly better than that of the control group (P < .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.


Assuntos
Motivação , Neoplasias do Colo do Útero , Humanos , Feminino , Qualidade de Vida , Estudos Retrospectivos , Neoplasias do Colo do Útero/cirurgia , Sono , Dor
16.
Am J Transl Res ; 16(3): 864-872, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586099

RESUMO

OBJECTIVE: To analyze the efficacy of arthroscopic treatment for patients with rotator cuff injuries and frozen shoulder combined with rotator cuff injuries and assess the factors influencing patient prognosis. METHODS: A retrospective analysis was performed on 85 patients who underwent arthroscopic surgery at Hanzhong Central Hospital between October 2016 and October 2021, including 42 patients treated for rotator cuff injuries alone (Group A), and 43 patients for frozen shoulder combined with rotator cuff injuries (Group B). Both groups underwent general anesthesia with controlled hypotension during surgery. Treatment outcomes, including shoulder joint functional scores, pain scores, shoulder joint range of motion, and muscle strength were assessed and compared between the two groups before treatment, as well as at 2 weeks and 2 months post-treatment. Quality of life was also evaluated and compared at 2 months post-treatment. Patients were categorized into good and poor prognosis groups based on their outcome, and factors influencing patient prognosis were analyzed. RESULTS: Before treatment, both groups exhibited relatively low shoulder joint function scores and external rotation angles, coupled with higher pain scores; however, these differences were not significant between groups (all P>0.05). The surgery duration for Group B was notably longer than that of Group A (P<0.05). Nevertheless, there was no significant variance in intraoperative blood loss between the two groups (P>0.05). After a 2-week treatment duration, both groups demonstrated a significant improvement in shoulder joint function score, pain score, and shoulder joint range of motion compared to baseline, but with no statistically significant intergroup differences. However, two months after the treatment, patients in Group A exhibited marked improvements in shoulder joint function score, pain score, shoulder joint range of motion, and overall quality of life compared to Group B (all P<0.05). Furthermore, the therapeutic efficacy in Group A was superior to that in Group B at the 2-month follow-up (P<0.05). Age, comorbid diabetes, metabolic disorders such as thyroid dysfunction, and the extent of shoulder cuff injury were identified as independent risk factors influencing prognosis. CONCLUSION: Arthroscopic treatment is effective for both frozen shoulder combined with rotator cuff injury and rotator cuff injury alone, with better outcomes observed in patients with rotator cuff injury only. This technique warrants further promotion.

17.
Immun Inflamm Dis ; 12(4): e1237, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577984

RESUMO

BACKGROUND: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. METHODS: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to quantify inflammatory factors (IL-1ß, IL-6, TNF-α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α-SMA, TGF-ß1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining. RESULTS: In vivo, CVB3-AMG487 reduced cardiac injury, α-SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL-1ß, IL-6, and TNF-α). In vitro, CXCL4/CXCR3B axis activation TGF-ß1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation. CONCLUSION: CXCL4 acts as a profibrotic factor in TGF-ß1/Smad2/3 pathway-induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.


Assuntos
Acetamidas , Infecções por Coxsackievirus , Miocardite , Pirimidinonas , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa , Interleucina-6 , Colágeno , Fibrose
18.
Nutr Res ; 125: 79-90, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552503

RESUMO

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.


Assuntos
Neoplasias Colorretais , Dieta , Fragilidade , Inflamação , Interleucina-10 , Interleucina-6 , Humanos , Neoplasias Colorretais/sangue , Estudos Transversais , Masculino , Feminino , Fragilidade/sangue , Inflamação/sangue , Idoso , Interleucina-6/sangue , Interleucina-10/sangue , Pessoa de Meia-Idade , Biomarcadores/sangue
19.
Chin J Traumatol ; 27(3): 153-162, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38458896

RESUMO

PURPOSE: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. METHODS: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q1, Q3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. RESULTS: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 - 25.42, p = 0.002), 2.85 (95% CI: 1.11 - 7.31, p = 0.030), 2.62 (95% CI: 1.12 - 6.13, p = 0.027), 2.44 (95% CI: 1.25 - 4.76, p = 0.009), and 1.5 (95% CI: 1.10 - 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. CONCLUSION: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.


Assuntos
Acidentes de Trânsito , Edema Encefálico , Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/complicações , Fatores de Risco , Masculino , Feminino , Estudos de Casos e Controles , Edema Encefálico/etiologia , Edema Encefálico/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Modelos Logísticos
20.
Brain Res Bull ; 210: 110928, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493836

RESUMO

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic.


Assuntos
Disfunção Cognitiva , Epilepsia , Humanos , Camundongos , Animais , Proteína-Lisina 6-Oxidase/genética , Proteína-Lisina 6-Oxidase/metabolismo , Aminopropionitrilo/farmacologia , Regulação da Expressão Gênica , Modelos Animais de Doenças , Disfunção Cognitiva/tratamento farmacológico
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