ABSTRACT
Retinal injury may be exacerbated by iron overload. Astragaloside IV (AS-IV) has potential applications in the food and healthcare industry to promote eye health. We sought to determine the mechanisms responsible for the protective effects of AS-IV on photoreceptor and retinal pigment epithelium cell death induced by iron overload. We conducted in vitro and in vivo experiments involving AS-IV pretreatment. We tested AS-IV for its ability to protect iron-overload mice from retinal injury. In particular, we analyzed the effects of AS-IV on iron overload-induced ferroptosis in 661W and ARPE-19 cells. AS-IV not only attenuated iron deposition and retinal injury in iron-overload mice but also effectively reduced iron overload-induced ferroptotic cell death in 661W and ARPE-19 cells. AS-IV effectively prevented ferroptosis by inhibiting iron accumulation and lipid peroxidation. In addition, inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) eliminated the protective effect of AS-IV against ferroptosis. The results suggest that ferroptosis might be a significant cause of retinal cell death associated with iron overload. AS-IV provides protection from iron overload-induced ferroptosis, partly by activating the Nrf2 signaling pathway.
Subject(s)
Ferroptosis , Iron Overload , Mice, Inbred C57BL , Retinal Pigment Epithelium , Saponins , Triterpenes , Ferroptosis/drug effects , Animals , Triterpenes/pharmacology , Triterpenes/therapeutic use , Saponins/pharmacology , Iron Overload/metabolism , Iron Overload/drug therapy , Mice , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology , Disease Models, Animal , Lipid Peroxidation/drug effects , Humans , Retinal Diseases/prevention & control , Retinal Diseases/metabolism , Retinal Diseases/pathology , Retinal Diseases/drug therapy , NF-E2-Related Factor 2/metabolism , Blotting, Western , Male , Iron/metabolismABSTRACT
RATIONALE AND OBJECTIVES: Hematoma expansion (HE) in intracerebral hemorrhage (ICH) is a critical factor affecting patient outcomes, yet effective clinical tools for predicting HE are currently lacking. We aim to develop a fully automated framework based on deep learning for predicting HE using only clinical non-contrast CT (NCCT) scans. MATERIALS AND METHODS: A large retrospective dataset (n = 2484) was collected from 84 centers, while a prospective dataset (n = 500) was obtained from 26 additional centers. Baseline NCCT scans and follow-up NCCT scans were conducted within 6 h and 48 h from symptom onset, respectively. HE was defined as a volume increase of more than 6 mL on the follow-up NCCT. The retrospective dataset was divided into a training set (n = 1876) and a validation set (n = 608) by patient inclusion time. A two-stage framework was trained to predict HE, and its performance was evaluated on both the validation and prospective sets. Receiver operating characteristics area under the curve (AUC), sensitivity, and specificity were leveraged. RESULTS: Our two-stage framework achieved an AUC of 0.760 (95% CI 0.724-0.799) on the retrospective validation set and 0.806 (95% CI 0.750-0.859) on the prospective set, outperforming the commonly used BAT score, which had AUCs of 0.582 and 0.699, respectively. CONCLUSION: Our framework can automatically and robustly identify ICH patients at high risk of HE using admission head NCCT scans, providing more accurate predictions than the BAT score.
ABSTRACT
Determining visual attention during cognitive tasks using activation MRI remains challenging. This study aimed to develop a new eye-tracking (ET) post-processing platform to enhance data accuracy, validate the feasibility of subsequent ET-fMRI applications, and provide tool support. Sixteen volunteers aged 18 to 20 were exposed to a visual temporal paradigm with changing images of objects and faces in various locations while their eye movements were recorded using an MRI-compatible ET system. The results indicate that the accuracy of the data significantly improved after post-processing. Participants generally maintained their visual attention on the screen, with mean gaze positions ranging from 89.1% to 99.9%. In cognitive tasks, the gaze positions showed adherence to instructions, with means ranging from 46.2% to 50%. Temporal consistency assessments indicated prolonged visual tasks can lead to decreased attention during certain tasks. The proposed methodology effectively identified and quantified visual artifacts and losses, providing a precise measure of visual attention. This study offers a robust framework for future work integrating filtered eye-tracking data with fMRI analyses, supporting cognitive neuroscience research.
Subject(s)
Artifacts , Attention , Cognition , Eye Movements , Eye-Tracking Technology , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Attention/physiology , Male , Female , Young Adult , Eye Movements/physiology , Adolescent , Cognition/physiology , AdultABSTRACT
Exploration of factors originating from brown adipose tissue that govern the thermogenic adipocyte differentiation is imperative for comprehending the regulatory framework underlying brown fat biogenesis and for devising therapeutic approaches for metabolic disorders associated with obesity. Prior evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating thermogenesis within adipose tissue. Here, we aimed to explore and identify the critical lncRNA that could promote thermogenic adipocyte differentiation and to provide a novel strategy to treat obesity-related metabolic diseases in the future. In this study, through amalgamation with our previous lncRNA microarray data from small extracellular vesicles derived from BAT (sEV-BAT), we have identified sEV-BAT-enriched lncRNA AK029592 as a critical constituent of the thermogenic program, which actively fostered beige adipocyte differentiation and enhanced the thermogenic capacities of adipose tissue. Moreover, lncRNA AK029592 could sponge miR-199a-5p in adipocytes to stimulate thermogenic gene expression. Consequently, we concluded lncRNA AK029592 as a crucial lncRNA component of the thermogenic program that regulated beige adipocyte differentiation and white adipose tissue browning, thereby providing a novel therapeutic target and strategy in combating obesity and related metabolic diseases.
ABSTRACT
OBJECTIVE: The 5-year survival rate of early-stage non-small cell lung cancer (NSCLC) is still not optimistic. We aimed to construct prognostic tools using clinicopathological (CP) and serum 8-miRNA panel to predict the risk of overall survival (OS) in early-stage NSCLC. MATERIALS AND METHODS: A total of 799 patients with early-stage NSCLC, treated between April 2008 and September 2019, were included in this study. A sub-group of patients with serum samples, 280, were analyzed for miRNA profiling. The primary endpoint of the study was OS. The CP panel for prognosis was developed using multivariate and forward stepwise selection analyses. The serum 8-miRNA panel was developed using the miRNAs that were significant for prognosis, screened using real-time quantitative PCR (qPCR) followed by differential, univariate and Cox regression analyses. The combined model was developed using CP panel and serum 8-miRNA panel. The predictive performance of the panels and the combined model was evaluated using the area under curve (AUC) values of receiver operating characteristics (ROC) curves and Kaplan-Meier survival analysis. RESULT: The prognostic panels and the combined model (comprising CP panel and serum 8-miRNA panel) was used to classify the patients into high-risk and low-risk groups. The OS rates of these two groups were significantly different (P<0.05). The two panels had higher AUC than the two guidelines, and the combined model had the highest AUC. The AUC of the combined model (AUC=0.788; 95 %CI 0.706-0.871) was better than that of the National Comprehensive Cancer Network (NCCN) guideline (AUC=0.601; 95 %CI 0.505-0.697) and Chinese Society of Clinical Oncology (CSCO) guideline (AUC=0.614; 95 %CI 0.520-0.708). CONCLUSION: The combined model based on CP panel and serum 8-miRNA panel allows better prognostic risk stratification of patients with early-stage NSCLC to predict risk of OS.
ABSTRACT
Droughts are increasingly frequent as the Earth warms, presenting adaptation challenges for ecosystems and human communities worldwide. A strategic environmental assessment (SEA) and the integration of adaptation strategies into policies, plans, and programs (PPP) are two important approaches for enhancing climate resilience and fostering sustainable development. This study developed an innovative approach to strengthen the SEA of droughts by quantifying the impacts of future temperature increases. A novel method for projecting drought events was integrated into the SEA process by leveraging multiple data sources, including atmospheric reanalysis, reconstructions, satellite-based observations, and model simulations. We identified drought conditions using terrestrial water storage (TWS) anomalies and applied a random forest (RF) model for disentangling the drivers behind drought events. We then set two global warming targets (2.0 °C and 2.5 °C) and analyzed drought changes under three shared socioeconomic pathways (SSP126, SSP370, SSP585). In a 2.0 °C warming world, over 50 % of the global surface will face increased drought risk. With an additional 0.5 °C increase, >60 % of the land will be prone to further drought escalation. We utilized copulas to build the joint distribution for drought duration and severity, estimating the joint return periods (JRP) for bivariate drought hazard. In tropical and subtropical regions, JRP reductions exceeding half are projected for >33 % of the regional land surface under 2.0 °C warming and for >50 % under 2.5 °C warming. Finally, we projected the impacts of drought events on population and gross domestic product (GDP). Among the three SSPs, under SSP370, population exposure is highest and GDP exposure is minimal under 2.0 °C warming. Global GDP and population risks from drought are projected to increase by 37 % and 24 %, respectively, as warming continues. This study enhances the accuracy of SEA in addressing drought risks and vulnerabilities, supporting climate-resilient planning and adaptive strategies.
ABSTRACT
Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain (RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity is recovered in the presence of heparin sulfate, which targets the 'N354 pocket' to ease restrictions of conformational transition resulting in a 'RBD-up' state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell-cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer. Although it has a high mortality rate, there is currently no effective treatment for HCC. Lenvatinib has traditionally been used as the first-line treatment for advanced HCC (aHCC); however, resistance to this therapy is common. It can be difficult to select effective second-line drugs to overcome lenvatinib resistance when treating aHCC. For patients with aHCC, poor treatment efficacy can result in patients missing the optimal treatment window and can lead to an irreversible situation. Lenalidomide has begun to be used to treat HCC; however, to the best of our knowledge, its efficacy in patients with lenvatinib-resistant HCC remains to be reported on in the literature. The present case report, to the best of our knowledge, describes the first case in the literature of a patient with lenvatinib-resistant aHCC who achieved a partial response after the treatment regimen was switched to lenalidomide. The present case report provides a promising novel route for the treatment of lenvatinib-resistant HCC.
ABSTRACT
Selective recognition and enrichment of fullerenes (e.g., C60 and C70) remains challenging due to the same diameter and geometrical similarity. Herein, we report a hexagonal anthracene-based nanotube (1) through a one-pot Suzuki-Miyaura cross-coupling reaction. With anthracene-based side walls and pyridine linkers, 1 features a nano-scale tubular cavity measuring 1.2 nm in diameter and 0.9 nm in depth, along with pH-responsive properties. Interestingly, the electron-rich 1 shows high binding affinity (K a ≈ 106 M-1) and selectivity (K s ≈ 140) to C70 over C60 in toluene, resulting from their different contribution of π-π interactions with the host. The protonation of 1 simultaneously alters the electronic properties within the nanotube, resulting in the release of the fullerene guests. Lastly, the selective recognition and pH stimuli-responsive properties of the nanotube have been utilized to enrich C70 from its low-content mixtures of fullerenes in chloroform.
ABSTRACT
BACKGROUND: Fluoroquinolones (FQs) are widely used in livestock and poultry industry because of their satisfactory effects in preventing and treating bacterial infection. However, due to irrational use and poor biodegradability, FQs can easily remain in food animals and further enter the human body through the food chain. Therefore, accurate and sensitive detection of FQs residues in animal-origin food is significant. The traditional methods commonly used for FQs detection have some limitations. Ratiometric fluorescence detection technology has the advantages of fast, sensitive, self-correcting, and easy visualization. However, the reports on the use of ratiometric fluorescence probes for FQs detection are limited. RESULTS: In this work, a novel probe was proposed for ratiometric fluorescent analysis of FQs. In this probe, the fluorescence of dithioerythritol stabilized copper nanoclusters (DTE-Cu NCs) was significantly enhanced due to the Tb3+ triggered aggregation-induced emission effect. FQs bound Tb3+ in Tb3+/DTE-Cu NCs through carboxyl and carbonyl groups, so that Tb3+ was effectively sensitized to emit green fluorescence. However, the red fluorescence of DTE-Cu NCs was not interfered. The fluorescence of the probe transformed from red to green with the increase of FQs concentration. Using norfloxacin (NOR), difloxacin (DIF), and enrofloxacin (ENR) as FQs simulants, this probe showed a sensitive linear response ranged from 0.025 to 22.5 µM, with the limits of detection of 9.6 nM, 9.3 nM, and 7.7 nM. The application potential for FQs detection was verified via a standard addition assay of egg samples with the recovery rate of 90.4 %-114.7 %. SIGNIFICANT: The fluorescence probe based on Tb3+/DTE-Cu NCs is expected to realize the ratiometric fluorescence sensitive detection of FQs. The establishment of this simple, effective, and rapid detection platform opens up a new way for the detection of FQs residues in animal-origin foods, and also provides a new idea for the design of rapid detection platforms for other hazard factors.
Subject(s)
Copper , Fluorescent Dyes , Fluoroquinolones , Terbium , Copper/chemistry , Copper/analysis , Fluoroquinolones/analysis , Fluoroquinolones/chemistry , Fluorescent Dyes/chemistry , Terbium/chemistry , Spectrometry, Fluorescence , Metal Nanoparticles/chemistry , Animals , Limit of DetectionABSTRACT
Polyploid giant cancer cells (PGCCs) are characterized by the presence of either a single enlarged nucleus or multiple nuclei and are closely associated with tumor progression and treatment resistance. These cells contribute significantly to cellular heterogeneity and can arise from various stressors, including radiation, chemotherapy, hypoxia, and environmental factors. The formation of PGCCs can occur through mechanisms such as endoreplication, cell fusion, cytokinesis failure, mitotic slippage, or cell cannibalism. Notably, PGCCs exhibit traits similar to cancer stem cells (CSCs) and generate highly invasive progeny through asymmetric division. The presence of PGCCs and their progeny is pivotal in conferring resistance to chemotherapy and radiation, as well as facilitating tumor recurrence and metastasis. This review provides a comprehensive analysis of the origins, potential formation mechanisms, stressors, unique characteristics, and regulatory pathways of PGCCs, alongside therapeutic strategies targeting these cells. The objective is to enhance the understanding of PGCC initiation and progression, offering novel insights into tumor biology.
ABSTRACT
OBJECTIVE: Early adolescence is marked by elevated psychopathology, including disrupted eating attitudes and behaviors. Reward processing is an identified mechanism in portending eating pathology, that is, aberrant reward responsivity may contribute to disrupted reward-seeking behaviors (e.g., food consuming). This literature has focused on adults or mid-to-late adolescents, with little work done on early adolescence. We examined the linkages between reward feedback processing, indexed by event-related potentials (ERPs), and changes of emerging disordered eating in community-dwelling early adolescents. METHOD: At T1, 115 youths (66 girls, mean/SD age = 11.00/1.16 years) completed an EEG monetary reward Doors task. Youths completed the Eating Disorder Examination-Questionnaire Short at T1 and ~6 months (T2) and ~12 months (T3) after T1. In the ERP data, we isolated a reward positivity (RewP) and a late positive potential (LPP) via principal component analysis. We applied multilevel modeling to examine whether baseline ERPs interacted with Time in predicting disordered eating and whether these interactions varied by sex. RESULTS: We found a significant Time × LPP interaction in girls but not boys. Among girls, only those with a smaller LPP toward the losses (versus wins), which might reflect suboptimal evaluation and regulatory processes in undesired situations, showed increases in disordered eating from T1 to T3. DISCUSSION: We provided preliminary yet novel evidence concerning the prospective associations between reward processing and changes of disordered eating in early adolescents. Future studies along this line will be critical for understanding the early mechanisms of eating pathology, identifying youths at risk, and developing prevention strategies.
ABSTRACT
BACKGROUND: Winter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the key cis-regulatory elements and precise mechanisms governing this process in wheat remain largely unknown. RESULTS: In this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues-leaf, axillary bud, and shoot apex-during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream of VRN3, contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with the VRN1 promoter and VRN3 distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering. CONCLUSIONS: Our study offers critical insights into wheat vernalization's epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to the VRN1 promoter and VRN3 distal regulatory elements.
Subject(s)
Gene Expression Regulation, Plant , Triticum , Vernalization , Cold Temperature , Epigenesis, Genetic , Epigenomics , Flowers/genetics , Flowers/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Regulatory Sequences, Nucleic Acid , Triticum/genetics , Triticum/growth & development , Vernalization/geneticsABSTRACT
Extreme value theory (EVT) models have been frequently utilized to estimate crash risk from traffic conflicts with the peak over threshold commonly used to identify conflict extremes. However, a common problem for the peak over threshold method is the selection of a suitable threshold to distinguish general and extreme conflicts. Subjective and arbitrary selection of the threshold in peak over threshold method can result in bias and unstable estimation results. The primary objective of the study is to propose a hybrid modelling approach for the threshold determination in peak over threshold method. The hybrid model consists of a joint gamma distribution and generalized Pareto distribution (GPD). The gamma distribution is used to fit general conflicts while the GPD is used to fit extreme conflicts. Specially, discontinued, continued and differentiable gamma-GPD models are developed with the threshold being treated as a model parameter. Traffic conflict data collected from three signalized intersections in the city of Surrey, British Columbia were used for the study. The modified time to collision (MTTC) was employed as conflict indicator. The Bayesian approach was employed to estimate the threshold as well as other hybrid gamma-GPD model parameters. The results show that the discontinued gamma-GPD model is superior to the continued and differentiable gamma-GPD models for determining the threshold in terms of crash estimation accuracy and model fit. The crash estimates using the threshold determined by the hybrid gamma-GPD model outperform those estimated based on the traditional quantile plots method, indicating that the superiority of the proposed threshold determination approach based on gamma-GPD hybrid model. The proposed hybrid gamma-GPD model could determine the threshold parameter in peak over threshold method for traffic conflicts extremes automatically in an objective and quantitative way. It contributes to existing peak over threshold method for producing reliable crash estimation.
Subject(s)
Accidents, Traffic , Bayes Theorem , Humans , Accidents, Traffic/prevention & control , Accidents, Traffic/statistics & numerical data , British Columbia , Models, Statistical , Risk Assessment/methods , Time FactorsABSTRACT
The transition to adolescence is characterized by rapid development of puberty, reward processing, and internalizing psychopathology (i.e., depression and anxiety). More advanced pubertal status and altered reward processing are both known to be associated with elevated internalizing symptoms. However, it was unclear to what extent pubertal status and reward processing interacted with each other in predicting internalizing psychopathology. We examined how the puberty-psychopathology association was moderated by the reward processing indexed by ERPs, including the reward positivity (RewP) and the late positive potential (LPP). A-hundred-and-fifteen nine-to-12-year-old typically developing youths (66 girls; Mean age/SD =10.98/1.18 years) reported their pubertal status and symptoms of depression and social anxiety and completed an EEG Doors task that assessed monetary reward feedback processing. A principal component analysis of the ERP data identified a RewP, an anterior LPP, and a posterior LPP, elicited by the win and loss feedback of the task. The puberty-social anxiety relationship was moderated by the RewP, an identified neural marker of reward sensitivity. Specifically, more advanced puberty was associated with heightened social anxiety symptoms in the presence of a larger, but not smaller, RewP. We did not observe any moderating effect of the LPPs. Our study provided novel evidence that a hypersensitivity toward the reward stimuli (indexed by an enlarged RewP) further exacerbated the risks associated with more advanced pubertal status for social anxiety.
Subject(s)
Anxiety , Electroencephalography , Evoked Potentials , Puberty , Reward , Humans , Female , Male , Puberty/physiology , Puberty/psychology , Child , Evoked Potentials/physiology , Anxiety/physiopathologyABSTRACT
Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated using magnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. One month after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD.
Subject(s)
Neuromyelitis Optica , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnosis , Middle Aged , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/immunology , Neuromyelitis Optica/etiology , Neuromyelitis Optica/complications , Aquaporin 4/immunology , Dysgerminoma/diagnosis , Dysgerminoma/complications , Dysgerminoma/pathology , Autoantibodies/blood , Autoantibodies/immunology , Magnetic Resonance ImagingABSTRACT
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, with its prevalence linked to both genetic predisposition and environmental factors. Epigenetic modifications, particularly through histone deacetylases (HDACs), have been recognized for their significant influence on DM pathogenesis. This review focuses on the classification of HDACs, their role in DM and its complications, and the potential therapeutic applications of HDAC inhibitors. HDACs, which modulate gene expression without altering DNA sequences, are categorized into four classes with distinct functions and tissue specificity. HDAC inhibitors (HDACi) have shown efficacy in various diseases, including DM, by targeting these enzymes. The review highlights how HDACs regulate ß-cell function, insulin sensitivity, and hepatic gluconeogenesis in DM, as well as their impact on diabetic cardiomyopathy, nephropathy, and retinopathy. Finally, we suggest that targeted histone modification is expected to become a key method for the treatment of diabetes and its complications. The study of HDACi offers insights into new treatment strategies for DM and its associated complications.
Subject(s)
Diabetes Complications , Diabetes Mellitus , Histone Deacetylase Inhibitors , Histone Deacetylases , Humans , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Animals , Diabetes Mellitus/drug therapy , Diabetes Complications/drug therapy , Epigenesis, Genetic/drug effectsABSTRACT
OBJECTIVES: To observe the effect of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on transient receptor potential vanilloid type 1(TRPV1), calcitonin gene-related peptide (CGRP), and serum interleukin-10 (IL-10) in the myocardial tissue of rats with chronic heart failure (CHF), so as to explore its underlying mechanisms in improvement of CHF. METHODS: Male SD rats were randomly divided into the normal, model, moxibustion, capsaicin, moxibustion + capsaicin, and moxibustion + solvent groups, with 10 rats in each group. The CHF model was established by permanent ligation of the anterior descending branch of the left coronary artery. Mild moxibustion was applied to bilateral BL13 and BL15 for 30 min once daily for 4 weeks. Rats in the capsaicin group were smeared with capsaicin in the acupoint area once a day for 4 weeks. For rats of the moxibustion + capsaicin and moxibustion + solvent groups, capsaicin and solvent were applied to the acupoint area before moxibustion for 4 weeks, respectively. The ejection fraction (EF) and left ventricular fractional shortening rate (FS) were examined by echocardiography. HE staining was used to observe the myecardial morphological structure. The mRNA and protein expression levels of TRPV1, CGRP and galectin-3 (Gal-3) in myocardial tissue were detected by real-time quantitative PCR and Western blot, respectively. The content of IL-10 in serum was detected by ELISA. RESULTS: After modeling, the pathological changes of myocardium (as cardiac muscle fiber disorder, inflammatory cell infiltration, etc.) were obvious, and the EF, FS, serum IL-10, protein and mRNA exspression of TRPV1 and CGRP were significantly decreased (P<0.01) in the model group compared with the normal group, while the protein and mRNA exspression of Gal-3 were significantly up-regulated (P<0.01). Following the interventions, the above-mentioned indexes were all reversed in moxibustion, capsaicin, and moxibustion + capsaicin groups (P<0.01), and the effect of moxibustion + capsaicin was the best (P<0.05, P<0.01). CONCLUSIONS: Moxibustion can reduce myocardial injury and improve cardiac function in CHF rats, which may be related to its effects in up-regulating the expression of TRPV1 and CGRP, and down-regulating the expression of Gal-3 to alleviate myocardial fibrosis.