Butyrate enhances erastin-induced ferroptosis of lung cancer cells via modulating the ATF3/SLC7A11 pathway.

Ferroptosis is a novel form of programmed cell death triggered by iron-dependent lipid peroxidation and has been associated with various diseases, including cancer. Erastin, an inhibitor of system Xc-, which plays a critical role in regulating ferroptosis, has been identified as an inducer of ferroptosis in cancer cells. In this study, we investigated the impact of butyrate, a short-chain fatty acid produced by gut microbiota, on erastin-induced ferroptosis in lung cancer cells. Our results demonstrated that butyrate significantly enhanced erastin-induced ferroptosis in lung cancer cells, as evidenced by increased lipid peroxidation and reduced expression of glutathione peroxidase 4 (GPX4). Mechanistically, we found that butyrate modulated the pathway involving activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11), leading to enhanced erastin-induced ferroptosis. Furthermore, partial reversal of the effect of butyrate on ferroptosis was observed upon knockdown of ATF3 or SLC7A11. Collectively, our findings indicate that butyrate enhances erastin-induced ferroptosis in lung cancer cells by modulating the ATF3/SLC7A11 pathway, suggesting its potential as a therapeutic agent for cancer treatment.

MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation.

PURPOSE: Long-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation. METHODS: miR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a. RESULTS: The expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-ß1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts. CONCLUSION: This data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.

Minimally Invasive Surgery for Coronary-Pulmonary Artery Fistula Via Parasternal Minithoracotomy.

Epicardial surgical repair has been proven to be effective for patients with coronary- pulmonary artery fistula (CPAF). However, most of the surgery has been performed through a median sternotomy under cardiopulmonary bypass. In this report, we describe a novel technique of performing minimally invasive surgery for CPAF patients without extracorporeal circulation via a parasternal minithoracotomy. This technique has proved to be safe and effective and may be worthy of use for patients with CPAF.

Prodigiosin Alleviates Pulmonary Fibrosis Through Inhibiting miRNA-410 and TGF-ß1/ADAMTS-1 Signaling Pathway.

BACKGROUND/AIMS: Pulmonary fibrosis is a common outcome of various interstitial lung diseases. Prodigiosin (PG) is a series of red pigment with methoxypyrrole ring. This studyinvestigates therole of prodigiosin in pulmonary fibrosis and its underlying mechanisms. METHODS: A pulmonary fibrosis rat model was established by intra-trachealinjection ofbleomycin A5. Rats were divided into 4 groups: Normal group, pulmonary fibrosis Model group, Prodigiosin treatment group and hydrocortisone treatmentgroup. HE and Masson staining were carried outto evaluate histopathological changes. The content of hydroxyproline in lung tissue was determined by alkaline hydrolysis. The expression of PICP and PIIINP was examined by ELISA. The mRNA expression of miR-410, TGF-ß1 and ADAMTS1 in lung homogenate were detected by RT-PCR. The bronchoalveolar lavage fluid (BALF) and lung tissues of rats were collected and analyzed. Human embryonic pulmonary fibroblast (HEPF) was used for study in vitro. A dual-luciferase reporter assay was conducted to examine the effect of miR-410 on ADAMTS1 expression. Cell transfection was conducted to inhibit miR-410. MTT assay was performed to investigate cell proliferation. The expressions of miR-410, TGF-ß1, ADAMTS1and other fibrosis related biomarkers (Col I, Col III, and α-SMA) wereexamined by RT-PCR and Western Blot. RESULTS: HE and Masson staining showed thickened alveolar septum, hyperplasticcapillaries, and large areas of collagen fiber deposition in pulmonary fibrosis model rats. Rats in prodigiosin and hydrocortisone treatment groups had alleviated symptoms. There was high hydroxyproline expression in model rats, whereas the expression of hydroxyproline reduced after prodigiosin or hydrocortisone treatments. RT-PCR results showed high miR-410,high TGF-ß1 and low ADAMTS1 in lung tissue of model rats. The expression of PICP and PIIINP werehigher in BALF of model group than in treatment groups. Prodigiosin and hydrocortisone treatment significantly reduced PICP and PIIINP content. RT-PCR and Western Blot analysis showed that prodigiosin inhibited expression of miR-410 and TGF-ß1, but up-regulated ADAMTS1 expression. MTT assay indicated that prodigiosin inhibited HEPF proliferation induced by miR-410 overexpression. CONCLUSION: Prodigiosin down-regulates the expression of miR-410 and TGF-ß1, up-regulates ADAMTS1, leading to decrease accumulation of fibrotic proteins. It could be used in alleviating pulmonary fibrosis.

Right minithoracotomy versus conventional median sternotomy for patients undergoing mitral valve surgery and Cox-maze IV ablation with entirely bipolar radiofrequency clamp.

Cox-maze IV ablation by bipolar radiofrequency clamp was considered to be only performed through median sternotomy (MS), but impossible through right minithoracotomy (RM). Now, we developed a novel technique of performing Cox-maze IV ablation entirely by bipolar clamp through RM. To compare the outcomes of RM or MS for patients undergoing mitral valve surgery and concomitant Cox-maze IV ablation with entirely bipolar clamp. All 152 patients underwent mitral valve surgery and concomitant Cox-maze IV ablation with bipolar clamp through RM (n = 69) or MS (n = 83) were analyzed for outcome differences. The etiology of mitral valve disease was rheumatic (n = 97) and degenerative (n = 55). All patients had long-standing persistent atrial fibrillation (AF). Diameter of left atrium ranged from 42 to 60 mm. All patients successfully underwent Cox-maze IV ablation by bipolar clamp. RM group had longer cardiopulmonary bypass time (130.3 ± 17.7 vs 115.3 ± 14.4 min; P < 0.001) and aortic cross-clamp time (91.8 ± 12.7 vs 74.6 ± 9.3 min; P < 0.001). But mechanical ventilation time (14.2 ± 6.6 vs 21.3 ± 9.0 h; P < 0.001) and hospital length of stay (9.3 ± 2.6 vs 11.7 ± 3.0 days; P < 0.001) were shorter in RM group. At discharge, the maintenance of normal sinus rhythm (NSR) was 94.2% in RM group and 95.1% in MS group (P = 1.000). Cumulative maintenance of NSR at 2 years postoperatively was 85.1 ± 5.8% in RM group and 88.6 ± 3.6% in MS group (P = 0.767). RM can achieve similar therapeutic effect to MS for patients undergoing mitral valve surgery and concomitant Cox-maze IV ablation with entirely bipolar clamp. In addition, patients through RM had faster recovery.

Stroke prevention following modified endoscopic ablation and appendectomy for atrial fibrillation.

We reported the results of stroke prevention following modified endoscopic procedure for atrial fibrillation. 82 patients underwent modified endoscopic procedure for atrial fibrillation (AF), in whom 47 had paroxysmal, 28 had persistent, and 7 had long-standing atrial fibrillation. CHA2DS2VASC median score was 3 (range from 0 to 8). The procedure was performed on the beating heart, through 3 ports on the left chest wall. Pulmonary vein isolation and ablation of the left atrium were achieved by bipolar radiofrequency ablation. Left atrial appendage (LAA) was excluded by stapler. Brain CT, cardiac CT and 24-h Holter monitoring were performed following the procedure. The procedure was successfully completed for all patients. The mean duration was 122 ± 40.1 min. LAA was excluded after appendectomy and checked by intraoperative transesophageal echocardiography. The mean follow-up duration was 24.3 ± 3.5 months. No patients showed signs and symptoms of transient ischemic attack or stroke. No new positive findings were demonstrated by recurring brain CT scan performed after the procedure. Cardiac CT confirmed the absence of LAA and thrombosis in the left atrium. 87.8 % (72/82) of all patients were in sinus rhythm. Our results demonstrate that the modified endoscopic procedure is a safe, effective, and appropriate treatment for AF, which restores sinus rhythm and may be associated with the prevention of AF-related stroke.

One-stage surgical treatment for Cantrell syndrome without repairing the left ventricular diverticulum: a case report.

Cantrell syndrome includes the defects of the heart, pericardium, diaphragm, abdominal wall, and sternum. The operative mortality is usually high. We report here a one-stage surgical correction in a case of Cantrell syndrome with left ventricular diverticulum.

Estimating sympathetic tone by recording subcutaneous nerve activity in ambulatory dogs.

INTRODUCTION: We tested the hypothesis that subcutaneous nerve activity (SCNA) of the thorax correlates with the stellate ganglion nerve activity (SGNA) and can be used to estimate the sympathetic tone. METHODS AND RESULTS: We implanted radio transmitters in 11 ambulatory dogs to record left SGNA, left thoracic vagal nerve activity (VNA), and left thoracic SCNA, including 3 with simultaneous video monitoring and nerve recording. Two additional dogs were studied under general anesthesia with apamin injected into the right stellate ganglion while the right SGNA and the right SCNA were recorded. There was a significant positive correlation between integrated SGNA (iSGNA) and integrated SCNA (iSCNA) in the first 7 ambulatory dogs, with correlation coefficient of 0.70 (95% confidence interval [CI] 0.61-0.84, P < 0.05 for each dog). Tachycardia episodes (heart rate exceeding 150 bpm for ≥3 seconds) were invariably preceded by SGNA and SCNA. There was circadian variation of both SCNA and SGNA. Crosstalk was ruled out because SGNA, VNA, and SCNA bursts had different timing and activation patterns. In an eighth dog, closely spaced bipolar subcutaneous electrodes also recorded SCNA, but with reduced signal to noise ratio. Video monitoring in additional 3 dogs showed that movement was not a cause of high frequency SCNA. The right SGNA correlated strongly with right SCNA and heart rate in 2 anesthetized dogs after apamin injection into the right stellate ganglion. CONCLUSIONS: SCNA recorded by bipolar subcutaneous electrodes correlates with the SGNA and can be used to estimate the sympathetic tone.

Analysis of the Synergistic Effects of Fasting Plasma Glucose and Hypertension on Cardiovascular Autonomic Neuropathy.

BACKGROUND: The purpose of this study was to evaluate the associations of fasting plasma glucose (FPG) and hypertension (HTN) with cardiovascular autonomic neuropathy (CAN) and to estimate the extent to which the synergistic effects of FPG and HTN affect outcomes in a Chinese population. METHOD: We conducted a large-scale, population-based study to analyze the association and interaction of the two factors with CAN in a sample of 2,092 Chinese people. Univariate and multiple linear regression (MLR) analyses were employed to detect these relationships. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction, the proportion attributable to interaction (AP), and the synergy index (S). RESULT: After adjusting for confounding factors, MLR showed that FPG and HTN were independently associated with CAN (p < 0.001 for both). A significant synergistic effect of FPG and HTN on CAN was detected (p = 0.046, RETI = 0.733, 95% CI 0.059-1.450; AP = 0.167, 95% CI -0.033 to 0.367; S = 1.275, 95% CI 0.140-2.410). CONCLUSION: Our findings suggest that FPG and HTN are independently associated with CAN, and they offer evidence to support the hypothesis that FPG and HTN have synergistic effects that influence the progression of CAN.

Efficacy and safety of novel epicardial circumferential left atrial ablation with pulmonary vein isolation in sustained atrial fibrillation.

The aim of this study was to examine the efficacy and safety of this novel epicardial circumferential left atrial ablation (CLAA) with pulmonary vein isolation (PVI) in sustained atrial fibrillation (AF). Thirty domestic pigs were divided equally into 3 groups: AF without ablation (AF group), AF with PVI (PVI group), and AF with CLAA and PVI (CLAA + PVI group). AF was induced by rapid atrial pacing. After AF was induced, CLAA and PVI were performed for pigs in CLAA + PVI group, and PVI was performed for pigs in PVI group. AF vulnerability, AF duration, and histology were performed in all groups. All pigs developed sustained AF after 6.27 ± 0.69 weeks of rapid atrial pacing. All pigs successfully underwent isolated PVI or CLAA with PVI on the beating heart in PVI group or CLAA + PVI group. Isolated PVI terminated AF in 3 of 20 pigs (15 %), and CLAA with PVI terminated AF in 5 of 8 pigs (62.5 %, P = 0.022). Compared with AF group (10/10), the incidence of sustained AF by burst pacing was significantly decreased in PVI group (3/10, P = 0.003) or CLAA + PVI group (0/10, P < 0.001). There was no significant difference between PVI group and CLAA + PVI group (P = 0.211). AF duration was significantly decreased in CLAA + PVI group (734.70 ± 177.81 s, 95 % CI 607.51-861.89) compared with PVI group (1217.90 ± 444.10 s, 95 % CI 900.21-1535.59, P = 0.008). Also, AF duration was significantly decreased in PVI group (P = 0.003) or CLAA + PVI group (P < 0.001) in comparison with AF duration in AF group (average 1800 s). Epicardial CLAA could ablate the left atrial roof and posterior wall together safely and reliably. Compared with PVI alone, CLAA with PVI may be able to improve the rate of acute termination of persistent AF. It may be useful in selecting the best ablation approaches for patients with persistent AF.

Effect of novel modified bipolar radiofrequency ablation for preoperative atrial fibrillation combined with off-pump coronary artery bypass grafting surgery.

We described a novel modified bipolar radiofrequency (RF) ablation for preoperative atrial fibrillation (AF) combined with off-pump coronary artery bypass grafting (OPCABG) for patients with AF and coronary artery disease (CAD). The aim of this study was to assess the effect of this novel procedure and to determine whether it can eliminate AF for CAD patients. From January 2007 to June 2013, 45 patients (26 male patients) with AF (9 paroxysmal, 17 persistent, and 19 long-standing persistent) and CAD underwent the novel modified bipolar RF ablation combined with OPCABG in our department. After median sternotomy, the modified bipolar RF ablation and OPCABG were performed on beating heart without cardiopulmonary bypass. Pulmonary vein isolation and left atrium ablation were achieved using a bipolar RF champ. Mitral annular lesion and ganglionic plexus were ablated with a bipolar RF pen. The left atrial appendage was excluded using a surgical stapler. 24 h holter monitoring and echocardiography were performed at discharge and 3, 6, 12 months postoperatively as well as every year thereafter. The modified bipolar RF ablation and OPCABG were performed successfully in all patients. Mean AF ablation time was 33.6 ± 4.2 min, and mean OPCABG time was 87.6 ± 13.3 min. Mean postoperative hospital stay was 12.6 ± 5.5 days. The maintenance of sinus rhythm was 95.6 % (43/45) at discharge. There was no early death and permanent pacemaker implantation in perioperation. At a mean follow-up of 29.8 ± 10.2 months, 38 of 45 (84.4 %) patients were in sinus rhythm. Follow-up TTE at 6 months postoperatively showed that left atrial diameter was significantly reduced and left ventricular ejection fraction was significantly increased. The novel modified bipolar RF ablation procedure was safe, feasible and effective. It may be useful in selecting the best ablation approaches for patients with AF and CAD.

Biatrial ablation versus limited right atrial ablation for atrial fibrillation associated with atrial septal defect in adults.

PURPOSE: To compare the efficacy and safety of limited right atrial ablation versus biatrial ablation for atrial fibrillation (AF) associated with atrial septal defect (ASD) in adults. METHODS: The subjects were 47 consecutive adult patients who underwent ASD closure with limited right atrial ablation (RA, n = 19) or biatrial ablation (BA, n = 28) for AF, between January, 2007 and December, 2012. Eighteen patients had persistent AF and 29 had long-standing persistent AF. Bipolar RF ablation was performed for all patients. RESULTS: AF ablation and ASD closure were performed successfully in all patients. The BA group had longer cardiopulmonary bypass time, aortic cross-clamp time, and hospital stay than the RA group, but the incidence of major postoperative complications was not significantly different between the groups. On discharge, normal sinus rhythm was maintained in 100% of the BA group patients and 78.9% of the RA group patients (P = 0.045). By 2 years postoperatively, cumulative maintenance of normal sinus rhythm off antiarrhythmic drugs was confirmed in 87.7 ± 6.7% of the BA group patients and 47.4 ± 11.5% of the RA group patients (P = 0.003). CONCLUSION: Biatrial ablation restored and maintained sinus rhythm more effectively than limited right atrial ablation, without increasing the risk of postoperative complications for AF associated with ASD in adults.

MiR-196a2 rs11614913 T>C Polymorphism is Associated with an Increased Risk of Tetralogy of Fallot in a Chinese Population.

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNAs that act as post-transcriptional gene regulatory elements. MiRNA polymorphisms may be associated with susceptibility to congenital heart disease (CHD). The aim of this study was to evaluate the impact of miRNA single nucleotide polymorphisms (SNPs) on CHD susceptibility. METHODS: We genotyped two functional SNPs, miR-196a2 rs11614913 and miR-146a rs2910164, in a case-control cohort of 173 Chinese patients with tetralogy of Fallot (TOF) and 207 non-CHD controls. RESULTS: When the miR-196a2 rs11614913 TT homozygote genotype was used as the reference group, the TC genotype was not associated with an increased risk of TOF. The CC genotype was associated with a borderline significantly increased risk for TOF. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of TOF (OR = 1.96, 95% CI = 1.18-3.25, p = 0.01). The miR-146a rs2910164 C>G polymorphism was not associated with developing TOF. CONCLUSIONS: Our findings suggested that the miR-196a2 rs11614913 T>C polymorphism may play a role in the development of TOF. Future larger studies that include populations of other ethnicities are required to confirm these findings. KEY WORDS: Congenital heart disease; MiRNA; Molecular epidemiology; Polymorphisms; Tetralogy of Fallot.

The early and mid-term results of mitral valve repair for mitral regurgitation in children.

PURPOSE: To review the surgical techniques and mid-term results of mitral valve repair in children with moderate or severe mitral regurgitation (MR). METHODS: One hundred and seven children with moderate or severe MR, aged 19.6 ± 8.5 months, were enrolled in this study. The surgical techniques used for mitral valve repair varied according to the mitral valve morphology, and included annuloplasty, annuloplasty ring, cleft closure, reconstruction of the posterior leaflet, etc. The concomitant cardiac anomalies were treated simultaneously. The results of repair were evaluated by transesophageal echocardiography performed during the operation and by serial transthoracic echocardiography performed during the follow-up. RESULTS: One hundred and six cases had no more than mild regurgitation intraoperatively, whereas only one case had moderate regurgitation. This patient underwent redo repair immediately, and the subsequent regurgitation was trivial. The in-hospital mortality rate was 0.9 % (1/107). The average follow-up was 46.5 ± 8.2 months. One patient died of heart failure 10 months postoperatively. The freedom from moderate or severe regurgitation after mitral valve repair was 92.3 ± 3.3 %. CONCLUSION: Pediatric patients with moderate or severe MR require early surgical treatment. The early and mid-term results of mitral valve repair in pediatric patients were satisfactory.

Application of endovascular occlusion of both caval veins in minimally invasive isolated redo tricuspid surgery through right thoracotomy.

OBJECTIVE: To summarise the experiences of applying vena cava endovascular occlusion technique in minimally invasive isolated redo tricuspid surgery. METHODS: Forty-six consecutive patients received minimally invasive redo tricuspid surgery through right thoracotomy at our institute. All the patients had isolated significant tricuspid regurgitation after previous cardiac surgeries. Preoperative chest computed tomography showed high risk of conventional median sternotomy and vena cava exposure. A right anterolateral thoracotomy incision was made from the fourth intercostal space. The arterial cannula was placed in femoral artery, and balloon cannulas were used for bicaval cannulation. The venous cannulation was guided by transoesophageal echocardiography. Tricuspid valve operation was performed with heart beating after both venous cannulas were endovascularly occluded by inflating the balloons. RESULTS: There were no complications related to this cannulation technique. Two patients needed position adjustment or re-inflation of the balloon to obtain complete occlusion. The average time of cardiopulmonary bypass establishment was 55 ± 15 min and pump time was 58 ± 23 min. The length of stay was 8 ± 7 days. There was no early death in hospital. CONCLUSION: Endovascular occlusion of both vena cava in isolated redo tricuspid surgery was safe, effective and reliable. This approach significantly simplified the complexity of the surgery.

Surgical treatment of atrial fibrillation in mitral valve surgery: a narrative review.

Background and Objective: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice, which leads to cardiac decompensation, cardiovascular and cerebrovascular infarction, and other thromboembolic diseases. AF is one of the most common comorbidities of valvular heart disease, especially in mitral valve disease. At the time of their mitral valve surgery, 20-42% of patients have AF. It is beneficial to maintain postoperative sinus rhythm and minimize complications when AF surgery is performed concurrently with mitral valve surgery. This review describes the surgical management of AF in mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. The aim of this review is to enable more patients with AF to receive more appropriate and individualised treatment. Methods: A narrative review was conducted on the literature on PubMed, Embase including all relevant studies published until November 2023. Key Content and Findings: This review focuses on the surgical management of AF during mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. Conclusions: Mitral valve surgery combined with AF surgery facilitates the maintenance of postoperative sinus rhythm in patients, reduces the risk of postoperative stroke, and improves survival. Advances in ablation technology have reduced the difficulty of the procedure, making it possible for more patients to undergo surgical ablation. In the future, it will be possible to tailor specific lesion sets and ablation modalities for individual patients. This would make surgical treatment of AF more effective and applicable to a larger population of patients with AF and mitral valve disease.

Development of neuromodulation for atrial fibrillation: a narrative review.

Background and Objective: Atrial fibrillation (AF) is a prevalent clinical arrhythmia with a high incidence of disability and mortality. Autonomic nervous system (ANS) plays a crucial role in the onset and persistence of AF, and can lead to electrophysiological changes and alterations in atrial structure. Both animal models and clinical findings suggest that parasympathetic and sympathetic activity within the cardiac ANS could induce atrial remodeling and AF. Remodeling of the cardiac autonomic nerves is a significant structural basis for promoting AF. Given the challenges faced by conventional pharmacological and atrial ablation techniques in the treatment of AF, increasing attention has been paid to autonomic intervention strategies for AF. Current research has demonstrated that the frequency and severity of AF episodes can be significantly reduced by modulating the activity of ANS. ANS neuromodulation is expected to lead more effective and personalized treatment options for patients with AF. The objective of this review is to provide a broader perspective for future related studies by reviewing preclinical and clinical studies of neuromodulation methods for the treatment of AF, searching for relevant approaches to treat AF, as well as identifying the strengths and weaknesses demonstrated by current relevant studies, and providing researchers with a broader overview of the latest neurological treatments for AF. Methods: A narrative review was conducted on the literature on PubMed, WanFang data, and Google Scholar, including all relevant studies published until November 2023. Key Content and Findings: In this review, we delve into the innervation of cardiac autonomic nerves, the role of the ANS in the development and maintenance of AF, and the current neuromodulation methods for AF treatment. These methods include stellate ganglion (SG) resection or ablation, vagus nerve stimulation (VNS), thoracic subcutaneous nerve stimulation (ScNS), renal denervation (RDN) therapy, ganglionated plexus (GP) ablation, and epicardial botulinum toxin or CaCl2 injection. More and more research suggests that neuromodulation methods for the treatment of AF have broad prospects. Conclusions: ANS plays a crucial role in AF development and maintenance through cardiac autonomic nerve remodeling. Modulating ANS activity can significantly reduce AF frequency and severity, offering more personalized treatment options. Current research on autonomic interventions for AF shows promise for more effective and personalized treatments.

Butyrate attenuates the stemness of lung cancer cells through lysosome Fe2+- and SLC7A11-mediated ferroptosis.

Cancer stem cells (CSCs) are considered key contributors to tumor progression, and ferroptosis has been identified as a potential target for CSCs. We have previously shown that butyrate enhances the ferroptosis induced by erastin in lung cancer cell, this study aimed to investigate the impact of butyrate on the progression of lung CSCs. To investigate these effects, we constructed a series of in vitro experiments, including 3D non-adherent sphere-formation, cytometry analysis, assessment of CSC marker expression, cell migration assay, and in vivo tumorigenesis analyses. Additionally, the influence of butyrate on chemotherapeutic sensitivity were determined through both in vitro and in vivo experiments. Mechanistically, immunofluorescence analysis was employed to examine the localization of biotin-conjugated butyrate. We identified that butyrate predominantly localized in the lysosome and concurrently recruited Fe2+ in lysosome. Moreover, butyrate reduced the stability of SLC7A11 protein stability in lung cancer cells through ubiquitination and proteasome degradation. Importantly, the effects of butyrate on lung CSCs were found to be dependent on lysosome Fe2+- and SLC7A11-mediated ferroptosis. In summary, our results demonstrate that butyrate could induce the ferroptosis in lung CSCs by recruiting Fe2+ in lysosome and promoting the ubiquitination-lysosome degradation of SLC7A11 protein.

Concurrent vs Staged Hybrid Ablation for Long-Standing Persistent Atrial Fibrillation: A Propensity-Matched Cohort Study.

BACKGROUND: Long-term success rates of catheter ablation (CA) for long-standing persistent atrial fibrillation (LSPAF) are less than satisfactory. Further improvement of ablation methods is crucial for enhancing the treatment of LSPAF. OBJECTIVES: This study sought to compare the outcomes of concurrent vs staged minimally invasive surgical-catheter hybrid ablation for LSPAF. METHODS: From December 2015 to December 2021, 104 matched patients (concurrent and staged, 1:1) were included in study. In the concurrent group, both left unilateral thoracoscopic epicardial ablation (EA) and CA were performed simultaneously in one procedure. In the staged group, EA was performed at the first hospitalization. If the patients experienced atrial fibrillation (AF) recurrence, CA was performed between 3 months and 1 year after EA. RESULTS: In the concurrent group, 4 patients were restored to sinus rhythm after EA, and 41 were patients restored to sinus rhythm during CA; 86.5% (45 of 52) achieved intraprocedural AF termination during concurrent hybrid ablation. In the staged group, all 52 patients underwent staged CA because of the recurrence of AF or atrial tachycardia (AT). Forty-seven (90.4%) patients achieved intraprocedural AF or AT termination during CA. Freedom from AF or AT off antiarrhythmic drugs at 2 years after hybrid ablation was 79.9% ± 5.7% in the concurrent group and 86.0% ± 4.9% in the staged group (P = 0.390). Failure of intraprocedural AF termination (HR: 14.378) was an independent risk factor for AF recurrence after hybrid ablation. CONCLUSIONS: Both concurrent and staged hybrid ablation could be safely and effectively applied to treat LSPAF. Improving the intraprocedural AF termination rate predicted better outcomes.

SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy.

Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin-like modifier (SUMO)-mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO-specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA-binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co-activator yes-associated protein 1 in the Hippo pathway. Finally, adeno-associated virus serotype 9 is used to construct TEAD1 wild-type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy-related heart failure.