The autophagic regulation of rosiglitazone-promoted adipocyte browning.

Objective: Browning of white adipocytes is considered an efficient approach to combat obesity. Rosiglitazone induces the thermogenetic program of white adipocytes, but the underlying mechanisms remain elusive. Methods: Expression levels of browning and autophagy flux markers were detected by real-time PCR and immunoblotting. H&E and Oil Red O staining were performed to evaluate the lipid droplets area. Nuclear protein extraction and immunoprecipitation were used to detect the proteins interaction. Results: In this study, we reported that rosiglitazone promoted adipocyte browning and inhibited autophagy. Rapamycin, an autophagy inducer, reversed adipocyte browning induced by rosiglitazone. Autophagy inhibition by rosiglitazone does not prevent mitochondrial clearance, which was considered to promote adipose whitening. Instead, autophagy inhibition increased p62 nuclear translocation and stabilized the PPARγ-RXRα heterodimer, which is an essential transcription factor for adipocyte browning. We found that rosiglitazone activated NRF2 in mature adipocytes. Inhibition of NRF2 by ML385 reversed autophagy inhibition and the pro-browning effect of rosiglitazone. Conclusion: Our study linked autophagy inhibition with rosiglitazone-promoted browning of adipocytes and provided a mechanistic insight into the pharmacological effects of rosiglitazone.

The beneficial and toxic effects of selenium on zebrafish. A systematic review of the literature.

Selenium is an important and essential trace element in organisms, but its effects on organisms are also a "double-edged sword". Selenium deficiency or excess can endanger the health of humans and animals. In order to thoroughly understand the nutritional value and toxicity hazards of selenium, researchers have conducted many studies on the model animal zebrafish. However, there is a lack of induction and summary of relevant research on which selenium acts on zebrafish. This paper provides a review of the reported studies. Firstly, this article summarizes the benefits of selenium on zebrafish from three aspects: Promoting growth, Enhancing immune function and anti-tumor ability, Antagonizing some pollutants, such as mercury. Then, three aspects of selenium toxicity to zebrafish are introduced: nervous system and behavior, reproductive system and growth, and damage to some organs. This article also describes how different forms of selenium compounds have different effects on zebrafish health. Finally, prospects for future research directions are presented.

Contrastive Graph Pooling for Explainable Classification of Brain Networks.

Functional magnetic resonance imaging (fMRI) is a commonly used technique to measure neural activation. Its application has been particularly important in identifying underlying neurodegenerative conditions such as Parkinson's, Alzheimer's, and Autism. Recent analysis of fMRI data models the brain as a graph and extracts features by graph neural networks (GNNs). However, the unique characteristics of fMRI data require a special design of GNN. Tailoring GNN to generate effective and domain-explainable features remains challenging. In this paper, we propose a contrastive dual-attention block and a differentiable graph pooling method called ContrastPool to better utilize GNN for brain networks, meeting fMRI-specific requirements. We apply our method to 5 resting-state fMRI brain network datasets of 3 diseases and demonstrate its superiority over state-of-the-art baselines. Our case study confirms that the patterns extracted by our method match the domain knowledge in neuroscience literature, and disclose direct and interesting insights. Our contributions underscore the potential of ContrastPool for advancing the understanding of brain networks and neurodegenerative conditions. The source code is available at https://github.com/AngusMonroe/ContrastPool.

Mitochondrial-to-nuclear communications through multiple routes regulate cardiomyocyte proliferation.

The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research. Despite extensive investigations into the loss of regenerative potential during evolution and development, unlocking the mechanisms governing cardiomyocyte proliferation remains elusive. Two recent groundbreaking studies have provided fresh perspectives on mitochondrial-to-nuclear communication, shedding light on novel factors that regulate cardiomyocyte proliferation. The studies identified two mitochondrial processes, fatty acid oxidation and protein translation, as key players in restricting cardiomyocyte proliferation. Inhibition of these processes led to increased cell cycle activity in cardiomyocytes, mediated by reduction in H3k4me3 levels through accumulated α-ketoglutarate (αKG), and activation of the mitochondrial unfolded protein response (UPRmt), respectively. In this research highlight, we discuss the novel insights into mitochondrial-to-nuclear communication presented in these studies, the broad implications in cardiomyocyte biology and cardiovascular diseases, as well as the intriguing scientific questions inspired by the studies that may facilitate future investigations into the detailed molecular mechanisms of cardiomyocyte metabolism, proliferation, and mitochondrial-to-nuclear communications.

A Generalized Cortico-Muscular-Cortical Network to Evaluate the Effects of Three-Week Brain Stimulation.

OBJECTIVE: Post-stroke transcranial magnetic stimulation (TMS) has gradually become a brain intervention to assist patients in the recovery of motor function. The long lasting regulatory of TMS may involve the coupling changes between cortex and muscles. However, the effects of multi-day TMS on motor recovery after stroke is unclear. METHODS: This study proposed to quantify the effects of three-week TMS on brain activity and muscles movement performance based on a generalized cortico-muscular-cortical network (gCMCN). The gCMCN-based features were further extracted and combined with the partial least squares (PLS) method to predict the Fugl-Meyer of upper extremity (FMUE) in stroke patients, thereby establishing an objective rehabilitation method that can evaluate the positive effects of continuous TMS on motor function. RESULTS: We found that the improvement of motor function after three-week TMS was significantly correlated with the complexity trend of information interaction between hemispheres and the intensity of corticomuscular coupling. In addition, the fitting coefficient ([Formula: see text]) for predicted and actual FMUE before and after TMS were 0.856 and 0.963, respectively, suggesting that the gCMCN-based measurement may be a promising method for evaluating the therapeutic effect of TMS. CONCLUSION: From the perspective of a novel brain-muscles network with dynamic contraction as the entry point, this work quantified TMS-induced connectivity differences while evaluating the potential efficacy of multi-day TMS. SIGNIFICANCE: It provides a unique insight for the further application of intervention therapy in the field of brain diseases.

The lysine 2-hydroxyisobutyrylome of Helicobacter pylori: Indicating potential roles of lysine 2-hydroxyisobutyrylation in the bacterial metabolism.

Helicobacter pylori (H. pylori) is a pathogen which colonizes the stomach, causing ulcers, chronic gastritis and other related diseases. Protein post-translational modifications (PTMs) in bacteria mainly include glycosylation, ubiquitination, nitrosylation, methylation, phosphorylation and acetylation, all of which have divergent functions in the physiology and pathology of the bacterium. Lysine 2-hydroxyisobutyrylation (Khib) is a newly discovered type of PTM in recent years in some kinds of organisms, and this PTM is involved in the regulation of a variety of metabolic process, such as bacterial glucose metabolism, lipid metabolism and protein synthesis. This study performed the first qualitative lysine 2-hydroxyisobutyrylome in H. pylori, and a total of 4419 Khib sites in 812 proteins were identified. The results show that Khib sites are mainly located in the key functional regions or active domains of proteins involved in nickel-trafficking, energy production, virulence factors, anti-oxidation, metal resistance, and ribosome biosynthesis in H. pylori. The study presented here provides new hints in the metabolism and pathology of H. pylori and the proteins with Khib modification may be potentially promising targets for the further development of antibiotics, especially considering the high occurrence of treatment failure of H. pylori failure due to development of antibiotics-resistance.

TPN10475 alleviates concanavalin A-induced autoimmune hepatitis by limiting T cell development and function through inhibition of PI3K-AKT pathway.

Autoimmune hepatitis (AIH) is an inflammatory liver disease in which the autoimmune system instigates an attack on the liver, causing inflammation and liver injury, and its incidence has increased worldwide in recent years. The mouse model of acute hepatitis established by concanavalin A (Con A) is a typical and recognized mouse model for the study of T-cell-dependent liver injury. In this study, we aimed to investigate whether the artemisinin derivative TPN10475 could alleviate AIH and its possible mechanisms. TPN10475 effectively inhibited lymphocyte proliferation and IFN-γ+ T cells production in vitro, alleviated liver injury by decreasing infiltrating inflammatory T cells producing IFN-γ in the liver and peripheral immune tissues, and demonstrated that TPN10475 weakened the activation and function of T cells by inhibiting PI3K-AKT signaling pathway. These results suggested that TPN10475 may be a potential drug for the treatment of AIH, and the inhibition of PI3K-AKT signaling pathway may provide new ideas for the study of the pathogenesis of AIH.

Revealing the effects and mechanisms of arbuscular mycorrhizal fungi on manganese uptake and detoxification in Rhus chinensis.

Arbuscular mycorrhizal fungi (AMF) can alleviate heavy metal phytotoxicity and promote plant growth, while the underlying mechanisms of AMF symbiosis with host plants under manganese (Mn) stress remain elusive. A pot experiment was carried out to investigate the plant growth, micro-structure, Mn accumulation, subcellular distribution, chemical forms, and physiological and biochemical response of Rhus chinensis inoculated with Funneliformis mosseae (FM) under different Mn treatments. The results showed that compared with plants without FM, FM-associated plants exhibited higher growth status, photosynthetic pigments, and photosynthesis under Mn stress. FM-associated plants were able to maintain greater integrity in mesophyll structure, higher thickness of leaf, upper epidermis, and lower epidermis under Mn treatment, and promote leaf growth. Mn accumulation in leaves (258.67-2230.50 mg kg-1), stems (132.67-1160.00 mg kg-1), and roots (360.92-2446.04 mg kg-1) of the seedlings inoculated with FM was higher than non-inoculated ones. FM-associated plants exhibited higher osmotic regulating substances and antioxidant enzymes' activities under Mn exposure, suggesting lower Mn toxicity in FM inoculated seedlings, despite the augment in Mn accumulation. After FM inoculation, Mn concentration (151.04-1211.32 mg kg-1) and percentage (64.41-78.55%) enhanced in the cell wall, whilst the transport of Mn to aerial plant organs decreased. Furthermore, FM symbiosis favored the conversion of Mn from high toxic forms (2.17-15.68% in FEthanol, 11.37-24.52% in Fdeionized water) to inactive forms (28.30-38.15% in FNaCl, 18.07-28.59% in FHAc, 4.41-17.99% in FHCl) with low phytotoxicity. Our study offers a theoretical basis for remediation of the FM- R. chinensis symbiotic system in Mn-contaminated environments.

The mechanisms of metronidazole resistance of Helicobacter pylori: A transcriptomic and biochemical study.

Helicobacter pylori (H. pylori) is a bacterial pathogen in the stomach, causing gastritis, gastric ulcer, duodenal ulcer and even gastric cancer. The triple therapy containing one bismuth-containing compound or a proton-pump inhibitor with two antibiotics was the cornerstone of the treatment of H. pylori infections. However the drug resistance of Helicobacter pylori is more and more common, which leads to the continued decline in the radical cure rate. The purpose of this study was to investigate the mechanism of metronidazole resistance of H. pylori through transcriptomics and biochemical characterizations. In this study, a 128-time-higher metronidazole-resistant H. pylori strain compared to the sensitive strain was domesticated, and 374 significantly differential genes were identified by transcriptomic sequencing as compared to the metronidazole-sensitive strain. Through GO and KEGG enrichment analysis, antibiotic-resistance pathways were found to be mainly involved in redox, biofilm formation and ABC transportation, and the results were verified by qRT-PCR. The subsequent biochemical analysis found that the urease activity of the drug-resistant strain decreased, and whereas the capabilities of bacterial energy production, membrane production and diffusion ability increased. The work here will drop hints for the mechanisms of antibiotic-resistance of H. pylori and provide promising biomarkers for the further development of new-kind drugs to treat metronidazole-resistant H. pylori.

Decoupling effect and driving factors of carbon footprint in megacity Wuhan, Central China.

Background: China's 35 largest cities, including Wuhan, are inhabited by approximately 18% of the Chinese population, and account for 40% energy consumption and greenhouse gas emissions. Wuhan is the only sub-provincial city in Central China and, as the eighth largest economy nationwide, has experienced a notable increase in energy consumption. However, major knowledge gaps exist in understanding the nexus of economic development and carbon footprint and their drivers in Wuhan. Methods: We studied Wuhan for the evolutionary characteristics of its carbon footprint (CF), the decoupling relationship between economic development and CF, and the essential drivers of CF. Based on the CF model, we quantified the dynamic trends of CF, carbon carrying capacity, carbon deficit, and carbon deficit pressure index from 2001 to 2020. We also adopted a decoupling model to clarify the coupled dynamics among total CF, its accounts, and economic development. We used the partial least squares method to analyze the influencing factors of Wuhan's CF and determine the main drivers. Results: The CF of Wuhan increased from 36.01 million t CO2eq in 2001 to 70.07 million t CO2eq in 2020, a growth rate of 94.61%, which was much faster than that of the carbon carrying capacity. The energy consumption account (84.15%) far exceeded other accounts, and was mostly contributed by raw coal, coke, and crude oil. The carbon deficit pressure index fluctuated in the range of 8.44-6.74%, indicating that Wuhan was in the relief zone and the mild enhancement zone during 2001-2020. Around the same time, Wuhan was in a transition stage between weak and strong CF decoupling and economic growth. The main driving factor of CF growth was the urban per capita residential building area, while energy consumption per unit of GDP was responsible for the CF decline. Conclusions: Our research highlights the interaction of urban ecological and economic systems, and that Wuhan's CF changes were mainly affected by four factors: city size, economic development, social consumption, and technological progress. The findings are of realistic significance in promoting low-carbon urban development and improving the city's sustainability, and the related policies can offer an excellent benchmark for other cities with similar challenges. Supplementary Information: The online version contains supplementary material available at 10.1186/s13717-023-00435-y.

Dual-roles of carbon black to accelerate phosphorus recovery as vivianite.

Carbon materials have been confirmed to promote phosphorus recovery as vivianite through enhancing dissimilatory iron reduction (DIR), which alleviates phosphorus crisis. Carbon black (CB) exhibits contradictory dual roles of cytotoxicity inducer and electron transfer bridge towards extracellular electron transfer (EET). Herein, the effect of CB on vivianite biosynthesis was investigated with dissimilatory iron reduction bacteria (DIRB) or sewage. With Geobacter sulfurreducens PCA as inoculum, the vivianite recovery efficiency increased accompanied with CB concentrations and enhanced by 39 % with 2000 mg·L-1 CB. G. sulfurreducens PCA activated the adaptation mechanism of secreting extracellular polymeric substance (EPS) to resist cytotoxicity of CB. While in sewage, the highest iron reduction efficiency of 64 % was obtained with 500 mg·L-1 CB, which was appropriate for functional bacterial selectivity like Proteobacteria and bio-transformation from Fe(III)-P to vivianite. The balance of CB's dual roles was regulated by inducing the adaptation of DIRB to gradient CB concentrations. This study provide an innovative perspective of carbon materials with dual roles for vivianite formation enhancement.

Hierarchical Trajectory Planning for Narrow-Space Automated Parking with Deep Reinforcement Learning: A Federated Learning Scheme.

Collision-free trajectory planning in narrow spaces has become one of the most challenging tasks in automated parking scenarios. Previous optimization-based approaches can generate accurate parking trajectories, but these methods cannot compute feasible solutions with extremely complex constraints in a limited time. Recent research uses neural-network-based approaches that can generate time-optimized parking trajectories in linear time. However, the generalization of these neural network models in different parking scenarios has not been considered thoroughly and the risk of privacy compromise exists in the case of centralized training. To address the above issues, this paper proposes a hierarchical trajectory planning method with deep reinforcement learning in the federated learning scheme (HALOES) to rapidly and accurately generate collision-free automated parking trajectories in multiple narrow spaces. HALOES is a federated learning based hierarchical trajectory planning method to fully exert high-level deep reinforcement learning and the low-level optimization-based approach. HALOES further fuse the deep reinforcement learning model parameters to improve the generalization capabilities with a decentralized training scheme. The federated learning scheme in HALOES aims to protect the privacy of the vehicle's data during model parameter aggregation. Simulation results show that the proposed method can achieve efficient automatic parking in multiple narrow spaces, improve planning time from 12.15% to 66.02% compared to other state-of-the-art methods (e.g., hybrid A*, OBCA) and maintain the same level of trajectory accuracy while having great model generalization.

Does paraspinal muscle morphometry predict functional status and re-operation after lumbar spinal surgery? A systematic review and meta-analysis.

OBJECTIVES: Whether paraspinal muscle degeneration is related to poor clinical outcomes after lumbar surgery is still indistinct, which limits its clinical application. This study aimed to evaluate the predictive value of paraspinal muscle morphology on functional status and re-operation after lumbar spinal surgery. METHODS: A review of the literature was conducted using a total of 6917 articles identified from a search of PubMed, EMBASE, and Web of Science databases through September 2022. A full-text review of 140 studies was conducted based on criteria including an objective assessment of preoperative paraspinal muscle morphology including multifidus (MF), erector spinae (ES), and psoas major (PS) in addition to measuring its relationship to clinical outcomes including Oswestry disability index (ODI), pain and revision surgery. Meta-analysis was performed when required metrics could be calculated in ≥ three studies, otherwise vote counting model was a good alternative to show the effect direction of evidence. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. RESULTS: A total of 10 studies were included in this review. Of them, five studies with required metrics were included in the meta-analysis. The meta-analysis suggested that higher preoperative fat infiltration (FI) of MF could predict higher postoperative ODI scores (SMD = 0.33, 95% CI 0.16-0.50, p = 0.0001). For postoperative pain, MF FI could also be an effective predictor for persistent low back pain after surgery (SMD = 0.17, 95% CI 0.02-0.31, p = 0.03). However, in the vote count model, limited evidence was presented for the prognostic effects of ES and PS on postoperative functional status and symptoms. In terms of revision surgery, there was conflicting evidence that FI of MF and ES could predict the incidence of revision surgery in the vote count model. CONCLUSION: The assessment of MF FI could be a viable method to stratify patients with lumbar surgery by the risk of severe functional disability and low back pain. KEY POINTS: • The fat infiltration of multifidus can predict postoperative functional status and low back pain after lumbar spinal surgery. • The preoperative evaluation of paraspinal muscle morphology is conducive for surgeons.

Correlations between paraspinal extensor muscle endurance and clinical outcomes in preoperative LSS patients and clinical value of an endurance classification.

Background: Few study has investigated how paraspinal muscle endurance deteriorates in lumbar spinal stenosis (LSS) patients. In addition, little information is available on the relationship between clinical outcomes and the endurance of paraspinal muscles. Objective: To explore the correlation between paraspinal extensor muscle endurance, quality of life (QOL) and sagittal spinopelvic alignment. Besides, we attempted to propose a paraspinal extensor muscle endurance test (PEMET) classification for identifying the severity of clinical symptoms and sagittal imbalance in LSS patients. Methods: 171 hospitalized LSS patients and 100 healthy controls from the community were prospectively enrolled in this study. The paraspinal extensor endurance test was performed at baseline according to Ito test. The LSS patients were stratified into three groups based on the performance time of endurance test: grade I (<10s); grade II (10-60s); and grade III (>60s). Clinical measures of QOL included the visual analog scale scores (VAS) for back pain and leg pain and the Oswestry Disability Index (ODI). Sagittal alignment was analysed by standing posteroanterior and lateral whole spine X-ray in LSS patients. Results: The LSS group had a significantly shorter performance time of the endurance test than the control group. The paraspinal muscle endurance significantly correlated with VAS-back, VAS-leg, ODI, pelvic tilt, lumbar lordosis and sagittal vertical axis (SVA; all p < 0.05). In binary logistic regression, the performance time of the endurance test was an independent factor of both poor functional status (ODI >40; p = 0.005, OR = 0.985) and global sagittal imbalance (SVA >50 mm; p = 0.019, OR = 0.985). Based on PEMET classification, moving from the grade III group to the grade I group, there was progressive worsening in VAS-back and ODI (all adjusted p < 0.05). Moreover, the grade I group had significantly greater VAS- leg, less LL and greater SVA than the other two groups (all adjusted p < 0.05). Conclusion: Paraspinal muscle endurance was associated with QOL and sagittal spinopelvic alignment in LSS patients. A PEMET classification system has been constructed and has shown a correlation with QOL and sagittal imbalance. Translational potential statement: The PEMET classification system proposed in this study could be available for identifying the severity of clinical symptoms and sagittal imbalance during preoperative evaluation in LSS patients.

The application of artificial intelligence in spine surgery.

Due to its obvious advantages in processing big data and image information, the combination of artificial intelligence and medical care may profoundly change medical practice and promote the gradual transition from traditional clinical care to precision medicine mode. In this artical, we reviewed the relevant literatures and found that artificial intelligence was widely used in spine surgery. The application scenarios included etiology, diagnosis, treatment, postoperative prognosis and decision support systems of spinal diseases. The shift to artificial intelligence model in medicine constantly improved the level of doctors' diagnosis and treatment and the development of orthopedics.

Chinese Food Image Database for Eating and Appetite Studies.

Modern people live in an environment with ubiquitous food cues, including food advertisements, videos, and smells. Do these food cues change people's eating behavior? Since diet plays a crucial role in maintaining health, it has been researched for decades. As convenient alternatives for real food, food images are widely used in diet research. To date, researchers from Germany, Spain, and other countries have established food photo databases; however, these food pictures are not completely suitable for Chinese studies because of the ingredients and characteristics of Chinese food. The main goal of this research is to create a library of Chinese food images and to provide as complete a data reference as possible for future studies that use food images as experimental material. After standardized processing, we selected 508 common Chinese food pictures with high familiarity and recognizability and attached detailed classifications concerning taste, macronutrients, calories, and participants' emotional responses to the pictures. Additionally, with food pictures as material, we conducted research on how people make dietary decisions in order to identify the variables that may affect a person's food choices. The effects of individual perceived healthiness and palatability, gender, BMI, family income, and levels of emotional and restricted eating were examined using eating decisions based on healthiness and palatability as dependent variables. The results showed that people with low household incomes are more likely to be influenced by food taste in their dietary decision-making process, while individuals with high household incomes are more likely to consider the healthy aspects of food. Moreover, parental BMI affects what children consume, with children who have parents with higher BMIs being more prone to overlook the healthiness value of food.

Can fat infiltration in the multifidus muscle be a predictor of postoperative symptoms and complications in patients undergoing lumbar fusion for degenerative lumbar spinal stenosis? A case-control study.

PURPOSE: This study aimed to explore whether 25% as the cutoff value of fat infiltration (FI) in multifidus (MF) could be a predictor of clinical outcomes of lumbar spinal stenosis (LSS) patients. METHODS: A total of 461 patients undergoing posterior lumbar interbody fusion for LSS with 1-year follow-up were identified. After sex- and age-match, 160 pairs of patients were divided into a FI < 25% group and a FI ≥ 25% group according to FI of MF at L4 on preoperative magnetic resonance imaging. Patient-reported outcomes including the visual analog scale scores (VAS) for back pain and leg pain and the Oswestry disability index (ODI) scores were evaluated. Bone nonunion and screw loosening were evaluated by dynamic X-ray. RESULTS: After matching, there was no significant difference in age, sex, body mass index, fusion to S1, number of fusion levels, osteoporosis, spondylolisthesis, smoking and diabetes. FI ≥ 25% group had significantly higher VAS for back pain, VAS for leg pain and ODI than FI < 25% group at 1-year follow-up. However, there was no significant difference in the change of them from baseline to 1-year follow-up between the two groups. In light of complications, FI ≥ 25% group had a significantly higher rate of bone nonunion than FI < 25% group, whereas there was no significant difference of screw loosening rates between the two groups. CONCLUSION: MF FI might be a pragmatic cutoff value to predict bone nonunion in LSS patients, but it has little predictive value on screw loosening and postoperative improvement of symptoms.

A Rapid Therapeutic Drug Monitoring Strategy of Carbamazepine in Serum by Using Coffee-Ring Effect Assisted Surface-Enhanced Raman Spectroscopy.

Carbamazepine (CBZ) has a narrow therapeutic concentration range, and therapeutic drug monitoring (TDM) is necessary for its safe and effective individualized medication. This study aims to develop a procedure for CBZ detection in serum using coffee-ring effect assisted surface-enhanced Raman spectroscopy (SERS). Silver nanoparticles deposited onto silicon wafers were used as the SERS-active material. Surface treatment optimization of the silicon wafers and the liquid-liquid extraction method were conducted to eliminate the influence of impurities on the silicon wafer surface and the protein matrix. The proposed detection procedure allows for the fast determination of CBZ in artificially spiked serum samples within a concentration range of 2.5-40 µg·mL-1, which matches the range of the drug concentrations in the serum after oral medication. The limit of detection for CBZ was found to be 0.01 µg·mL-1. The developed method allowed CBZ and its metabolites to be ultimately distinguished from real serum samples. The developed method is anticipated to be a potential tool for monitoring other drug concentrations.

Dynamic observation of 5-fluorouracil-induced myocardial injury and mitochondrial autophagy in aging rats.

Patients treated with 5-fluorouracil (5-FU) can develop rare but potentially severe cardiac effects, including cardiomyopathy, angina pectoris, heart failure and cardiogenic shock. The specific pathologies and underlying mechanisms are yet to be fully understood. The results of previous studies have indicated that mitochondrial autophagy is widely detected in many angiocardiopathies. In the present study, the dynamic changes in the homeostasis of mitochondrial injury and autophagy were observed in rats treated with 5-FU for different durations. A corresponding control group and a 5-FU model group were established in groups of Sprague-Dawley rats aged 2 and 18 months, and the myocardial enzyme levels were determined at different time points. At 2 weeks post-model establishment, cardiac ultrasound and myocardial histological staining were performed, cardiomyocyte apoptosis and myocardial mitochondrial function were assessed, and mitochondrial ultrastructure was examined. In addition, the expression levels of autophagy-related proteins were evaluated in the 18-month-old rats on days 7 and 14 of 5-FU administration. The experimental results demonstrated that 5-FU induced an elevation in the levels of myocardial enzymes, as well as changes in the cardiac structure and function, and that these changes were more prominent over longer drug durations. In addition, 5-FU decreased the levels of myocardial mitochondrial ATP and mitochondrial membrane potential, and aggravated myocardial fibrosis and cardiomyocyte apoptosis compared with those observed in the untreated control group, treated with the same volume of saline as 5-FU in the 5-FU group. These injuries were particularly evident in aging rats. Notably, 5-FU increased the expression levels of myocardial mitochondrial autophagy-related proteins, and electron microscopy revealed a more severe autophagic state in the model groups compared with that in the control groups. In conclusion, 5-FU induced myocardial mitochondrial damage, the degree of which was more severe in aging rats compared with that in young rats. The mitochondrial autophagy induced by 5-FU was excessive, and the degree of autophagy was aggravated with increased 5-FU administration time.