Metabolic subtypes and immune landscapes in esophageal squamous cell carcinoma: prognostic implications and potential for personalized therapies.

BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment. METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles. RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA. CONCLUSION: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.

High-fat stimulation induces atrial neural remodeling by reducing NO production via the CRIF1/eNOS/P21 axi.

BACKGROUND: Autonomic remodeling of the atria plays a pivotal role in the development of atrial fibrillation (AF) and exerts a substantial influence on the progression of this condition. Hyperlipidemia is a predisposing factor for AF, but its effect on atrial nerve remodeling is unclear. The primary goal of this study was to explore the possible mechanisms through which the consumption of a high-fat diet (HFD) induces remodeling of atrial nerves, and to identify novel targets for clinical intervention. METHODS: Cell models were created in vitro by subjecting cells to palmitic acid (PA), while rat models were established by feeding them a high-fat diet. To investigate the interplay between cardiomyocytes and nerve cells in a co-culture system, we utilized Transwell cell culture plates featuring a pore size of 0.4 µm. The CCK-8 assay was employed to determine cell viability, fluorescent probe DCFH-DA and flow cytometry were utilized for measuring ROS levels, JC-1 was used to assess the mitochondrial membrane potential, the Griess method was employed to measure the nitric oxide (NO) level in the supernatant, a fluorescence-based method was used to measure ATP levels, and MitoTracker was utilized for assessing mitochondrial morphology. The expression of pertinent proteins was evaluated using western blotting (WB) and immunohistochemistry techniques. SNAP was used to treat nerve cells in order to replicate a high-NO atmosphere, and the level of nitroso was assessed using the iodoTMT reagent labeling method. RESULTS: The study found that cardiomyocytes' mitochondrial morphology and function were impaired under high-fat stimulation, affecting nitric oxide (NO) production through the CRIF1/SIRT1/eNOS axis. In a coculture model, overexpression of eNOS in cardiomyocytes increased NO expression. Moreover, the increased Keap1 nitrosylation within neuronal cells facilitated the entry of Nrf2 into the nucleus, resulting in an augmentation of P21 transcription and a suppression of proliferation. Atrial neural remodeling occurred in the HFD rat model and was ameliorated by increasing myocardial tissue eNOS protein expression with trimetazidine (TMZ). CONCLUSIONS: Neural remodeling is triggered by high-fat stimulation, which decreases the production of NO through the CRIF1/eNOS/P21 axis. Additionally, TMZ prevents neural remodeling and reduces the occurrence of AF by enhancing eNOS expression.

Inhibition of sepsis-induced acute kidney injury via the circITCH-miR-579-3p-ZEB2 axis.

Circular RNAs (circRNAs) are linked to the regulation of sepsis-induced acute kidney injury (AKI). However, the function of circITCH in the development of sepsis-induced AKI is still unclear. The levels of circITCH, miR-579-3p and ZEB2 were examined by real-time PCR and immunoblotting. Then, the roles of circITCH in cell viability, apoptosis, and inflammation in lipopolysaccharide (LPS)-treated HK-2 cells were evaluated. The further mechanism was investigated using rescue assays. CircITCH was downregulated in septic AKI patients and LPS-triggered HK-2 cells. CircITCH overexpression restored cell viability in LPS-treated HK-2 cells and restrained apoptosis and inflammatory cytokine production. CircITCH negatively regulated miR-579-3p, thereby upregulating ZEB2 expression. Taken together, circITCH alleviates LPS-induced HK-2 cell injury by regulating miR-579-3p/ZEB2 signal axis, which provides a theoretical basis for AKI therapy.

Measurement and analysis of instantaneous microwave frequency based on an optical frequency comb.

A microwave photonics instantaneous frequency measurement scheme with 14 channels based on an optical frequency comb (OFC) is proposed. In this scheme, a 14-line flat OFC is generated by cascading a dual-parallel Mach-Zehnder modulator (DPMZM) with a Mach-Zehnder modulator (MZM). The intercepted microwave signal with multiple-frequency components can be measured by using DPMZM, Fabry-Perot filter (FPF), wavelength division multiplexer (WDM), and optical power detector array. This scheme can measure and analyze the frequency of microwave signals in the ranges of 0.5-13.5 GHz, 13.5-26.5 GHz, and 26.5-39.5 GHz with the measurement accuracy of ±0.5GHz. The reconfigurability of the system can be realized by adjusting the comb-line spacing of the OFC and the free spectral range (FSR) of the FPF.

Gender differences in the relationships between different types of childhood trauma and resilience on depressive symptoms among Chinese adolescents.

Growing studies have paid attention to the relationships between childhood trauma, resilience and depressive symptoms. Depression is more common in girls, while gender differences in these associations have been rarely studied. Yet the study will be beneficial for prevention and intervention of depression in adolescents. The aim of this study is to examine gender differences in the effects of different types of childhood trauma and resilience on depressive symptoms. Data was collected from 6510 students (3408 males, aged 10-17 years) in Wuhan, Hubei, China from 2015 to 2016. Participants completed a self-report questionnaire assessing childhood trauma, resilience, and depressive symptoms. Multiple regression analysis was used to determine gender differences in the relationships between childhood trauma, resilience and depressive symptoms. We found that childhood trauma was positively related to depressive symptoms for both genders, but the relationship in females was stronger than in males. No significant gender difference was found in the independent effect of resilience to depressive symptoms. Resilience moderated the effects of emotional abuse, physical abuse and sexual abuse on depressive symptoms in both males and females. However, the interaction effect of resilience with emotional abuse on depressive symptoms was stronger in females compared to males. Our findings revealed gender differences in the links between childhood trauma and depressive symptoms among adolescents, and the interaction effect of resilience and childhood emotional abuse on depressive symptoms was gender-specific. These provide the basis for gender-special prevention and intervention measures for depressive symptoms in adolescents.

Reliability and validity of the Chinese version of the LMC Skills, Confidence & Preparedness Index (SCPI) in patients with type 2 diabetes.

BACKGROUND: A variety of diabetes self-management instruments have been developed but few of them consist of the preparedness for diabetes self-management behavior. The novel psychometric evaluation tool "the LMC Skills, Confidence & Preparedness Index (SCPI)" measures three key aspects of a patient's diabetes self-management: knowledge of the skill, confidence in being able to perform skill and preparedness to implement the skill. The objective of this study was to translate, adapt and validate the SCPI for use in Chinese adult patients with type 2 diabetes. METHODS: This study followed the guideline recommended by the American Academy of Orthopaedic Surgeons Evidence Based Medicine Committee (AAOS) to indigenize the scale. Forward and back translation, and cross-cultural language debugging were completed according to the recommended steps. A convenience sample of Chinese patients with type 2 diabetes (n = 375) were recruited from a university-affiliated hospital in Shanghai. The validity (criterion, discriminant validity, and construct validity), reliability (internal consistency and test-retest reliability) and the interpretability of the instrument were examined. The content validity was calculated by experts' evaluation. RESULTS: The Chinese version of SCPI (C-SCPI) has good internal consistency with a Cronbach's alpha of 0.92. The ceiling effects of the preparedness subscales is 21%. The criterion validity of three dimensions of C-SCPI was established with significantly moderate correlations between the DKT, DES-SF and SDSCA (p < 0.05). The S-CVI of the whole scale was 0.83. Except for entry 21, the I-CVI values of all entries were greater than 0.78. The C-SCPI has also shown good discriminative validity with statistically significant differences between the patients with good and poor glycemic control. Confirmatory factor analysis showed that modified results indicate that the fitting degree of the model is good, χ2/df = 2.775, RMSEA = 0.069, CFI = 0.903, GFI = 0.873, TLI = 0.889, IFI = 0.904. The test-retest reliability coefficient was 0.61 (p < 0.01). CONCLUSION: We established a Chinese version of SCPI through translation and cross-cultural adaptation. The C-SCPI is reliable and valid for assessment of the level of self-management in Chinese patients with type 2 diabetes.

Relationship between serum uric acid levels and different types of atrial fibrillation: An updated meta-analysis.

AIM: Increasing evidence supports the hypothesis that high serum uric acid (SUA) levels are related to atrial fibrillation (AF). However, the incidence of AF in patients with hyperuricemia and SUA levels in different types of AF is not entirely clear. This meta-analysis was designed to evaluate the relationship between SUA and incidence of AF, and the variation in SUA levels in different types of AF. DATA SYNTHESIS: Relevant reports were searched for in Embase, PubMed and the Cochrane Library. A fixed-effects model combining relative risk (RR) and the corresponding 95% confidence interval (95% CI) was used to evaluate the correlation between SUA and AF. The standardized mean differences (SMDs) of SUA values were calculated using a random-effects model to evaluate the differences in SUA levels among different types of AF. A total of 31 studies with 504,958 participants were included in this research. The results from 8 cohort studies showed that high SUA levels significantly increased the incidence of AF [RR (95% CI): 1.92 (1.68-2.20); P < 0.01]. The results from 29 studies revealed that SUA levels elevated in patients with AF [SMD (95% CI): 0.55 (0.43-0.66); P < 0.001]. Meanwhile, SUA levels in new-onset AF [SMD (95%CI): 0.24 (0.10-0.38); P = 0.001], paroxysmal AF [SMD (95%CI): 0.52 (0.33-0.72); P < 0.001] and persistent AF [SMD (95%CI): 1.23 (0.98-1.48); P < 0.001] were significantly higher than that in patients without AF. CONCLUSIONS: High SUA levels had an obvious correlation with the occurrence rate of AF. In addition, SUA levels were significantly different among patients with new-onset, paroxysmal and persistent AF.

Long noncoding RNA TCONS-00106987 promotes atrial electrical remodelling during atrial fibrillation by sponging miR-26 to regulate KCNJ2.

Long noncoding RNAs (lncRNAs) have been suggested to play indispensable roles in multiple heart diseases. However, the correlations between lncRNAs and atrial fibrillation (AF) are unclear. In this study, we performed comprehensive lncRNA profiling via high-throughput RNA sequencing analysis using non-AF and AF rabbit models. Based on a series of filtering pipelines and bioinformatics analyses, TCONS-00106987 was selected for further research. TCONS-00106987 levels were increased in the atria during AF. Moreover, the atrial effective refractory period was shortened and the AF inducibility was increased in vivo in response to lentiviral-mediated up-regulation of TCONS-00106987. TCONS-00106987 repression resulted in the opposite effects. Further studies indicated that TCONS-00106987 expression was positively correlated with the expression of the protein-coding gene KCNJ2. Luciferase reporter assays and whole-cell patch-clamp recording confirmed that TCONS-00106987 promoted electrical remodelling via endogenous competition with microRNA-26 (miR-26) to induce transcription of its target gene KCNJ2, thereby increasing inward-rectifier K+ current (IK1 ). In conclusion, our study reveals a pathogenic lncRNA-miRNA regulatory network specific to atrial electrical remodelling that offers potential therapeutic targets for AF.

Tenacissoside H exerts an anti-inflammatory effect by regulating the nf-κb and p38 pathways in zebrafish.

Marsdenia tenacissima exhibits biological activity with heat-clearing and detoxifying properties, relieving coughs and asthma and exerting anticancer and anti-HIV effects. Tenacissioside H (TH) is a Chinese medicine monomer extracted from the dried stem of Marsdenia tenacissima. We investigated the in vivo anti-inflammatory activity of TH using three different zebrafish inflammation models: local inflammation induced by tail cutting, acute inflammation induced by CuSO4, and systemic inflammation induced by lipopolysaccharide (LPS). Real time-polymerase chain reaction (RT-PCR) was used to elucidate the mechanism of TH action against LPS-induced inflammatory responses. Our results showed TH significantly reduced the number of macrophages in the injured zebrafish tail, inhibited CuSO4-induced migration of macrophages toward the neural mound, and decreased the distribution of macrophages in tail fin compared to LPS-treated group. Furthermore, TH inhibits LPS-induced inflammation responses in zebrafish by modulating the nuclear factor κB (nf-κb) and p38 pathways to regulate inflammatory cytokines, such as tumor necrosis factor-α (tnf-α), cyclooxygenase (cox-2), interleukin-1b (il-1b), interleukin-8 (il-8), interleukin-10 (il-10), nitric oxide synthase (nos2b) and prostaglandin E synthase (ptges). In conclusion, TH possesses anti-inflammation activity via the regulation of the nf-κb and p38 pathways. This finding provides a reference for the clinical application of Xiaoaiping (the trade name of Marsdenia tenacissima extract).

GCH1 attenuates cardiac autonomic nervous remodeling in canines with atrial-tachypacing via tetrahydrobiopterin pathway regulated by microRNA-206.

BACKGROUND/AIMS: Cardiac autonomic nerve remodeling (ANR) is an important mechanism of atrial fibrillation (AF). GTP cyclohydrolase I, encoded by GCH1, is the rate-limiting enzyme in de novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthesis. Previous studies reported that increased BH4 and NO content negatively regulated nerve regeneration. This study investigated the effects of GCH1 on ANR via BH4 pathway, regulated by microRNA-206 (miR-206). METHODS AND RESULTS: In canines, atrial tachypacing (A-TP), together with miR-206 overexpression, increased PGP9.5 level and inhibited GCH1 expression by quantitative real-time polymerase chain reaction and western blot analysis. GCH1 was validated to be a direct target of miR-206 by luciferase assays. Meanwhile, miR-206 overexpression by lentiviruses infection into right superior pulmonary vein fat pad decreased GCH1 expression to ∼40% and further reduced BH4 and NO content compared with the control canines. After infection of GCH1 overexpression lentiviruses for two weeks, atrial effective refractory period was increased compared with the control group (105.8 ± 1.537 ms vs 99.17 ± 2.007 ms, P < 0.05). Moreover, GCH1 overexpression attenuated canines' atrial PGP9.5 level to ∼56% of the controls. In myocardial cells, transfection of GCH1 overexpression lentiviruses also decreased PGP9.5 expression to 26% of the control group. In patients, plasma was collected and miR-206 expression was upregulated in AF patients (n = 18) than the controls (n = 12). CONCLUSIONS: Our findings suggested that GCH1 downregulation exacerbated ANR by decreasing atrial BH4 and NO content modulated by miR-206 in A-TP canines. This indicates that GCH1 may prevent the initiation of AF through inhibiting ANR.

Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00075467 modulates atrial electrical remodeling by sponging miR-328 to regulate CACNA1C.

Electrical remodeling has been reported to play a major role in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) have been increasingly recognized as contributors to the pathology of heart diseases. However, the roles and mechanisms of lncRNAs in electrical remodeling during AF remain unknown. In this study, the lncRNA expression profiles of right atria were investigated in AF and non-AF rabbit models by using RNA sequencing technique and validated using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 99,843 putative new lncRNAs were identified, in which 1220 differentially expressed transcripts exhibited >2-fold change. Bioinformatics analysis was conducted to predict the functions and interactions of the aberrantly expressed genes. On the basis of a series of filtering pipelines, one lncRNA, TCONS_00075467, was selected to explore its effects and mechanisms on electrical remodeling. The atrial effective refractory period was shortened in vivo and the L-type calcium current and action potential duration were decreased in vitro by silencing of TCONS_00075467 with lentiviruses. Besides, the expression of miRNA-328 was negatively correlated with TCONS_00075467. We further demonstrated that TCONS_00075467 could sponge miRNA-328 in vitro and in vivo to regulate the downstream protein coding gene CACNA1C. In addition, miRNA-328 could partly reverse the effects of TCONS_00075467 on electrical remodeling. In summary, dysregulated lncRNAs may play important roles in modulating electrical remodeling during AF. Our study may facilitate the mechanism studies of lncRNAs in AF pathogenesis and provide potential therapeutic targets for AF.

Oxidative stress-mediated developmental toxicity induced by isoniazide in zebrafish embryos and larvae.

Isoniazide (INH) is an important first-line drug that is used to treat tuberculosis. However, the effect of INH on fetal growth has not yet been elucidated, and the mechanism of INH-induced developmental toxicity is still unknown. In the present study, we employed zebrafish embryos and larvae to investigate the developmental toxicity of INH. The survival rates of the embryos and larvae as well as the hatching rates of embryos were significantly reduced. Morphological abnormalities, including spinal curvature, yolk retention, swimming bladder absence, tail bending and shorter body lengths were induced by INH. Histopathological analysis showed loose cell-to-cell contacts and large vacuoles in the larval hepatocytes. Thin intestinal walls, frayed gut villi and widespread cell lysis were observed in the intestines of the larvae in the higher concentration (8, 16 mm) exposure groups. In addition, exposure to high doses (≥ 6 mm) of INH significantly reduced the locomotor capacity of the zebrafish larvae. INH significantly increased the levels of reactive oxygen species and malondialdehyde and decreased the superoxide dismutase activity in zebrafish larvae, which suggested that oxidative stress was induced and that the antioxidant capacity was inhibited. Superoxide dismutase 1 and liver fatty acid-binding protein mRNA levels were significantly downregulated, while the GSTP2 and cytochrome P450 3A mRNA levels were significantly upregulated in the INH-exposed zebrafish larvae. The overall results indicated that INH caused a dose- and time-dependent increase in developmental toxicity and that oxidative stress played an important role in the developmental toxicity induced by INH in zebrafish larvae. Copyright © 2017 John Wiley & Sons, Ltd.

Atrial Heterogeneous Autonomic Neural Remodeling in Rabbits with Experimental Atrial Fibrillation and the Effect of Intervention by Rosuvastatin.

BACKGROUND: The study aimed to observe the effects of pacing on the atrial effective refractory period (AERP), inducibility of atrial fibrillation (AF), and changes of atrial autonomic neural remodeling (ANR) by rosuvastatin intervention on the acute model of rapid-pacing-induced AF. METHODS: Thirty rabbits were randomly divided into a control group (C, n = 10), rapid-pacing group (P, n = 10), and rosuvastatin-intervention group (R, n = 10). AERP and inducibility of AF were measured for all groups. The sympathetic and parasympathetic nerves of left atrium, right atrium, and atrial septum labeled with tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) were detected by immunohistochemistry and Western blot. RESULTS: The AERP in group R was prolonged, and AF could not be induced as easily (P < 0.05). Immunohistochemistry showed that the densities and heterogeneity of TH and ChAT positive nerves of the atrium in group P were significantly higher than those in group C (ranked as right atrium > atrial septum > left atrium), whereas those in group R were decreased (P < 0.05). Western blot showed that TH and ChAT protein expression in group P was significantly increased compared with group C, but decreased in group R (P < 0.05). CONCLUSIONS: Persistent rapid atrial pacing can lead to heterogeneous ANR in different parts of the rabbit atrium and may cause AF, which can be reversed by rosuvastatin. The inhibitory function of rosuvastatin may be associated with its role in reversing atrial ANR.

Transcriptome analysis of canine cardiac fat pads: involvement of two novel long non-coding RNAs in atrial fibrillation neural remodeling.

Intrinsic cardiac autonomic neural remodeling (ANR) has been reported to be involved in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) are important orchestrators of gene regulatory networks. However, little is known about the relationships between lncRNAs and cardiac ANR in AF. In this study, second-generation RNA sequencing was performed to examine the transcriptomes of lncRNAs in AF and non-AF canine cardiac fat pads. A total of 61,616 putative lncRNAs were yielded, in which 166 were downregulated and 410 were upregulated with more than twofold change. Bioinformatics analysis showed that the aberrantly expressed genes were associated with neural development, migration and neurodegenerative disorders. On the basis of a series of filtering pipelines, two new lncRNAs, namely, TCONS_00032546 and TCONS_00026102, were selected. Silencing of TCONS_00032546 or TCONS_00026102 with lentiviruses in vivo could significantly shorten or prolong the atrial effective refractory period thereby increasing or preventing AF inducibility by promoting or inhibiting the neurogenesis. Besides, the expression of CCND1-FGF19-FGF4-FGF3 gene cluster and SLC25A4, the nearby genes of TCONS_00032546 and TCONS_00026102, were negatively correlated with that of lncRNAs. Furthermore, combining bioinformatics analysis with literature review, TCONS_00032546 and TCONS_00026102 may induce effects by increasing the CCND1-FGF19-FGF3-FGF4 gene cluster and SLC25A4 via complex mechanisms during neural remodeling. Taken together, dysregulated lncRNAs may play regulatory roles in AF neural remodeling, which may further provide potential therapeutic targets for prophylaxis and treatment of AF.

The effect of the left stellate ganglion on sympathetic neural remodeling of the left atrium in rats following myocardial infarction.

BACKGROUND: The neural remodeling of the atrium plays an important role in the initiation of atrial fibrillation after myocardial infarction (MI); however, the effects of the left stellate ganglion (LSG) on the neural remodeling of the atrium remain incompletely understood. Thus, this study investigated the mechanism by which the LSG mediates sympathetic neural remodeling of the left atrium (LA) in rats after MI. METHODS: Sixty rats were randomly divided into a Sham group and an MI group. The expression levels of growth-associated protein-43 (GAP43) and nerve growth factor (NGF) messenger ribonucleic acid (mRNA) were measured by reverse transcription polymerase chain reaction. Immunohistochemistry was used to detect the distribution and density of GAP43- and NGF-positive nerves. The expression levels of the proteins were quantified by Western blotting. RESULTS: Compared with the Sham group, GAP43 mRNA expression in the LSG was increased in the MI group (P < 0.01), but not significantly increased in the LA. Immunohistochemical analysis demonstrated that in both the LSG and the LA, the mean densities of GAP43- and NGF-positive nerves in the MI group were increased (P < 0.01). In both the LSG and the LA, the protein levels of GAP43 and NGF in the MI group were increased relative to the Sham group (P < 0.01). CONCLUSIONS: The increased levels of NGF and GAP43 proteins can induce sympathetic nerve hyperinnervation in the LSG and the LA after MI. The increased GAP43 proteins in the LA, which may have been transported from the LSG, accelerated LA sympathetic neural remodeling in rats.

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

BACKGROUND: Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. METHODS: Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. RESULTS: Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. CONCLUSION: Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN.

Rosuvastatin attenuates atrial structural remodelling in rats with myocardial infarction through the inhibition of the p38 MAPK signalling pathway.

OBJECTIVE: The purpose of this study was to verify the hypothesis that rosuvastatin attenuates atrial structural remodelling in rats with myocardial infarction (MI) through the regulation of the p38 mitogen-activated protein kinase (MAPK) signalling pathway. METHODS: A total of 66 rats were used in this study to establish a model of MI. The 56 rats that survived the first 24h after surgery were randomly divided into four groups: the control group (C group), the rosuvastatin group (R group), the low-dose torasemide group (T1 group), and the high-dose torasemide group (T2 group). The four groups of rats received daily intragastric administration of normal saline, rosuvastatin, or torasemide (T1: 1mg/kg body weight; T2: 2mg/kg body weight) for a total of four weeks. The rats in the sham-operated group (n=14) also received daily intragastric administration of normal saline for four weeks. After four weeks of intervention, the left ventricular end-diastolic pressure (LVEDP) was measured in all groups of rats by haemodynamic methods. The rats were then sacrificed, and the left atrial tissues were collected. The collagen volume fractions (CVFs) in the left atrial tissues were determined using Masson's trichrome staining. The expression of phosphorylated p38 (P-p38) MAPK in the left atrial tissues was examined by immunohistochemistry and western blot analysis. RESULTS: The results showed that LVEDP, CVF, and P-p38 MAPK expression were drastically elevated in the four MI groups in comparison to the sham-operated group (p<0.001). Rosuvastatin elevated the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF). Both rosuvastatin and torasemide improved the haemodynamic parameters. No significant difference was detected in LVEDP between the R group and the T1 group (p=0.37). In contrast, LVEDP was significantly higher in the R group than in the T2 group (p <0.05). CVF (%) was markedly decreased in the R group compared to the C, T1, and T2 groups (decreased by 47.4%, 28%, and 20.1%, respectively). Immunohistochemical analysis showed that the indices of P-p38 MAPK positive cells were significantly decreased in the R group in comparison with the C, T1, and T2 groups (decreased by 44.6%, 36.6%, and 21.4%, respectively). Western blot analysis demonstrated that P-p38 MAPK expression was markedly reduced in the R group compared with the C and T1 groups (reduced by 67% and 40.5%, respectively). The level of P-p38 MAPK in the R group was slightly higher than in the T2 group. However, the difference was not statistically significant (p>0.05). CONCLUSION: Rosuvastatin attenuates atrial structural remodelling in rats with MI. The mechanism underlying this phenomenon may be associated with the downregulation of P-p38 MAPK by rosuvastatin.

DDX56 promotes EMT and cancer stemness via MELK-FOXM1 axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major global cause of death, with epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties contributing to its metastasis. DEAD box helicase 56 (DDX56) is involved in carcinogenesis, but its role in EMT induction and stem phenotype maintenance is unclear. This study assessed the impact of DDX56 absence on HCC cell stemness and EMT. DDX56 was found to be overexpressed in HCC tissues, correlating with disease stage and prognosis. In vitro, DDX56 stimulated tumor cell proliferation, migration, invasion, EMT, and stemness. It also enhanced maternal embryonic leucine-zipper kinase (MELK)-mediated forkhead box protein M1 (FOXM1) expression, regulating cancer stemness and malignant traits. In vivo, DDX56 knockdown in tumor-bearing mice reduced tumorigenicity and lung metastasis by modulating the MELK-FOXM1 signaling pathway. Collectively, DDX56 initiates stem cell-like traits in HCC and promotes EMT via MELK-FOXM1 activation, shedding light on HCC pathogenesis and suggesting a potential anti-cancer therapeutic target.

[Retracted] Circular RNA NOX4 promotes the development of colorectal cancer via the microRNA­485­5p/CKS1B axis.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that there appeared to be a matching data panel comparing between one of the Transwell invasion assay experiments (the 'SW620/si­NC' data panel) shown in Fig. 2F and Fig 6D in the following paper, written by different authors at different research institutes, that had already been published at the time of this paper's submission: Wang D, Yang T, Liu J, Liu Y, Xing N, He J, Yang J and Ai Y: Propofol inhibits the migration and invasion of glioma cells by blocking the PI3K/AKT pathway through miR­206/ROCK1 axis. Onco Targets Ther 13: 361­370, 2020. In addition, a potential problem regarding the design of the experiment was noted with the selection of the primers for the amplification of the miRNA miR­485­5p. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 44: 2009­2020, 2020; DOI: 10.3892/or.2020.7758].

lncRNA-056298 Regulates GAP43 and Promotes Cardiac Intrinsic Autonomic Nerve Remodelling in a Canine Model of Atrial Fibrillation Induction after Ganglionated Plexus Ablation.

BACKGROUND: Cardiac intrinsic autonomic nerve remodelling has been reported to play an important role in the recurrence of atrial fibrillation after radiofrequency ablation, which significantly affects the long-term efficacy of this procedure. lncRNAs have been shown to interact in the pathological processes underlying heart diseases. However, the roles and mechanisms of lncRNAs in cardiac intrinsic autonomic nerve remodelling during atrial fibrillation reduction after ganglionated plexus ablation remain unknown. OBJECTIVES: The aim of this study was to investigate the mechanism by which lncRNA- 056298 modulates GAP43 to affect cardiac intrinsic autonomic nerve remodelling and facilitate the induction of atrial fibrillation after ganglionated plexus ablation. METHODS: A canine model of right atrial ganglionated plexus ablation was established. The atrial electrophysiological characteristics and neural markers were detected before and after 6 months of ganglionated plexus ablation. High-throughput sequencing was used to screen differentially expressed lncRNAs in target atrial tissues, and lncRNA- 056298 was selected to further explore its effects and mechanisms on cardiac intrinsic autonomic nerve remodelling. RESULTS: The induction rate of atrial fibrillation increased in dogs after ganglionated plexus ablation. Overexpression of lncRNA-056298 by lentivirus can shorten the atrial effective refractory period and increase the induction of atrial fibrillation. lncRNA- 056298 promoted cardiac intrinsic autonomic nerve remodelling via endogenous competition with cfa-miR-185 to induce transcription of its target gene GAP43, thereby affecting the induction of atrial fibrillation. CONCLUSIONS: lncRNA-056298 regulates GAP43 by sponging miR-185, which affects cardiac intrinsic autonomic nerve remodelling and mediates atrial fibrillation induction after ganglionated plexus ablation.