Morphological risk of acute type A aortic dissection in the mildly to moderately dilated aorta.

OBJECTIVES: This study aimed to analyse and determine the role of aortic length and curvature in the pathogenesis of acute type A aortic dissection (ATAAD) with ascending aortic diameters (AADs) <5 cm. METHODS: We reviewed the clinical and imaging data of patients with ATAAD (n = 201) and ascending aortic dilation (n = 83). Thoracic aortic bending index (TABI) was used to quantify aortic curvature and analyse its role in ATAAD below the diameter risk threshold. RESULTS: The AAD was <5.0 and <4.0 cm in 78% and 37% of patients with ATAAD, respectively. The median ascending aortic length (AAL) was 104.6 mm (Q1-Q3, 96.5-113.6 mm), and in 62.7% of patients, it was <11 cm. The median TABI was 14.99 mm/cm (Q1-Q3, 14.18-15.86 mm/cm). Patients with ATAAD and those with aortic dilation were matched for AAD, age, sex, height and other clinical factors. After matched, the dissection group had higher AALs (median, 102.9 mm; Q1-Q3, 96.0-112.5 mm vs median, 88.2 mm; Q1-Q3, 83.7-95.9 mm; P < 0.001) and TABI (median, 14.84 mm/cm; Q1-Q3, 14.06-15.83 mm/cm vs median, 13.55 mm/cm; Q1-Q3, 13.03-14.28 mm/cm; P < 0.001). According to the regression analysis, the area under the curve required to distinguish patients with ATAAD from those with aortic dilation was 0.831 in AAL, 0.837 in TABI and 0.907 when AAL was combined with TABI. CONCLUSIONS: The patients with ATAAD had higher AAL and TABI than those with aortic dilation. The combination of TABI and AAL might be a potential morphological marker for determining ATAAD risk below the current aortic diameter risk threshold.

MEGF6 prevents sepsis-induced acute lung injury in mice.

OBJECTIVE: Acute lung injury (ALI) is featured as excessive inflammatory response and oxidative damage, and results in high death rate of septic patients. This research intends to determine the function of multiple EGF like domains 6 (MEGF6) in sepsis-induced ALI. METHODS: Mice were intratracheally treated with adenovirus to knock down or overexpress MEGF6 in lung tissues, and then were subjected to cecum ligation and puncture (CLP) operation to induce ALI. Primary peritoneal macrophages were isolated, and were knocked down or overexpressed with MEGF6, and then, were stimulated with lipopolysaccharide (LPS) to confirm its role in vitro. RESULTS: Serum and lung MEGF6 levels were significantly elevated in septic mice. MEGF6 knockdown exacerbated, while MEGF6 overexpression prevented inflammation, oxidative damage and ALI in CLP mice. Meanwhile, LPS-elicited inflammatory response and oxidative damage in primary macrophages were reduced by MEGF6 overexpression, but were further aggravated by MEGF6 knockdown. Mechanistic studies revealed that MEGF6 reduced cluster of differentiation 38 (CD38) expression and subsequently elevated intracellular nicotinamide adenine dinucleotide levels, thereby activating sirtuin 1 (SIRT1) without affecting the protein expression. SIRT1 suppression or CD38 overexpression with either genetic or pharmacologic methods remarkably blunted the lung protective effects of MEGF6 in CLP mice. CONCLUSION: MEGF6 prevents CLP-induced ALI through CD38/SIRT1 pathway, and it might be a valuable therapeutic candidate for the management of sepsis-induced ALI.

Limonin, a novel AMPK activator, protects against LPS-induced acute lung injury.

AMP-activated protein kinase (AMPK) activation plays crucial roles in the treatment of many oxidative stress- and inflammation-induced diseases, including acute lung injury (ALI). Limonin is a naturally occurring tetracyclic triterpenoid extracted from the plants of Rutaceae and Meliaceae. Limonin also serves as an AMPK activator with anti-inflammatory and anti-oxidation effects. However, the potential beneficial effects of limonin on ALI and the possible mechanisms have never been disclosed till now. Here, the effects of limonin on lipopolysaccharide (LPS)-induced ALI in C57 BL/6 mice, plus bone marrow-derived macrophages (BMDM) stimulated with LPS to induce in vitro ALI model were investigated. Limonin significantly improved pulmonary function and alleviated lung pathological injury in LPS-induced mice. Meanwhile, limonin also markedly decreased inflammation and oxidative stress in lung tissues from LPS-treated mice. In vitro experiments also unveiled that limonin could decrease inflammation and oxidative stress in LPS-induced BMDM in a concentration-dependent manner. Mechanically, limonin could promote the activation of AMPKα and upregulate the expression of nuclear factor erythroid 2-related factor 2 (NRF2) in lung tissues and BMDM. Pharmacological inhibition of AMPKα by Compound C or AMPKα knockout could abolish the pulmonary protection from limonin during ALI. In conclusion, limonin mediates the activation of AMPKα/NRF2 pathway, providing an attractive therapeutic target for ALI in the future.

Nesfatin-1, a novel energy-regulating peptide, alleviates pulmonary fibrosis by blocking TGF-ß1/Smad pathway in an AMPKα-dependent manner.

Pulmonary fibrosis is a chronic progressive disease which steadily causes a critical public health concern. Nesfatin-1, a novel energy-regulating peptide discovered in 2006, could increase the level of AMPK phosphorylation. Previous studies have unveiled that Nesfatin-1 possessed many pharmacological effects including anti-inflammation, anti-oxidative stress, anti-fibrosis, and the regulation of lipid metabolism. Here, we investigated the impact of Nesfatin-1 on pulmonary fibrosis. Male C57BL/6J mice were intraperitoneally injected with Nesfatin-1 (10 µg·kg-1·day-1) for 21 days since mice were intratracheally administrated with bleomycin (BLM) (2 U/kg). Primary murine lung fibroblasts were stimulated with TGF-ß1 (10 ng/ml) for 48 h. The results showed that Nesfatin-1 treatment significantly improved pulmonary function and decreased the production of collagen in BLM-treated mice. Meantime, Nesfatin-1 treatment also inhibited oxidative stress and inflammation in lung tissues from BLM-treated mice. Mechanically, Nesfatin-1 blocked the activation of TGF-ß1/Smad2/3 signaling pathway in lung tissues challenged with BLM. In addition, we found that Nesfatin-1 enhanced the phosphorylation of AMPKα during pulmonary fibrosis. However, pharmacological inhibition or genetic deletion of AMPKα could both offset the pulmonary protection mediated by Nesfatin-1 during pulmonary fibrosis. Our experimental results firstly show Nesfatin-1 might serve as a novel treatment or adjuvant against pulmonary fibrosis by blocking TGF-ß1/Smad pathway in an AMPKα-dependent manner.

Two-Centimeter Single-Port Incision Minimizing Intercostal Nerve Damage Applied in Video-Assisted Thoracoscopic Surgery Segmentectomy for Pulmonary Ground Glass Nodules.

Purposes: We introduced a novel modified 2-cm single-port incision made by blunt separation minimizing intercostal muscle and nerve damage applied in video-assisted thoracoscopic surgery (VATS) segmentectomy, and compared it with the traditional single-port incision or the novel incision plus a 3-mm tiny port, aiming to explore a more minimally invasive single-port technique for VATS segmentectomy. Materials and Methods: We retrospectively analyzed the clinical data of 174 pulmonary ground glass nodule patients who received single-port VATS segmentectomy (54 modified 2-cm single port, 67 modified single port plus tiny port, and 53 traditional single port, respectively) in our medical center from May 2020 to December 2022. Three kinds of approaches were compared retrospectively, concerning their safety, feasibility, and postoperative pain. Results: There were no serious complications and mortality in either group. The blood loss, tube duration, and hospitalization time were comparable among the three groups (P > .05). The 2-cm single-port and 2-cm single-port plus tiny-port group were obviously more advantageous in the visual analog scores of postoperative pain, the wound numbness, incision healing and appearance than that in the traditional group (P < .05), while they were comparable. Notably, the operation time of the 2-cm plus tiny-port group was shorter than that of the 2-cm group (P < .05) and similar to the traditional single-port group. Conclusions: The 2-cm modified single-port applied for VATS segmentectomy is feasible and safe, and has obviously advantages in postoperative pain, numbness, and appearance of incision. With addition of tiny port, the convenience of the operation can be significantly increased without increasing pain. Our finding could provide a promising new incision mode for VATS segmentectomy.

A catechol bioadhesive for rapid hemostasis and healing of traumatic internal organs and major arteries.

Uncontrolled hemorrhage caused by trauma to internal organs or major arteries poses critical threats to lives. However, rapid hemostasis followed by tissue repair remains an intractable challenge in surgery owing to the lack of ideal internal-use adhesives that can achieve fast and robust wet adhesion and accelerate wound healing. Herein, we develop a robust hemostatic bioadhesive (CAGA) from novel highly-branched aminoethyl gelatin with end-grafted abundant catechol (Gel-AE-Ca). The unique chemical structure of Gel-AE-Ca makes CAGA capable of gelling on wet tissues via synergetic cross-linking of catechol-Fe3+ chelation and horseradish peroxidase (HRP)/H2O2-triggered covalent bonds using a dual-channel needle, meeting the key demands of internal medical applications (e.g., instant and strong wet adhesion, injectability, biocompatibility, self-healing, stretching flexibility, infection resistance, and proper biodegradability). It exhibits rapid gelation within 10 s and robust wet tissue adhesion up to 115.0 ± 13.1 kPa of shear strength and 245.0 ± 33.8 mm Hg of sealing strength. In vivo trials demonstrate that CAGA can not only effectively seal anastomosis of the carotid artery, but achieve rapid hemostasis on the sites of liver incisions and penetrating cardiac wounds within 10 s. The wound closure by CAGA and its timely biodegradation promote wound healing of the vital organs.

The Application of Two-Stage Operation for High-Risk Patients with Oesophageal Cancer Following Gastrectomy.

BACKGROUND: Oesophageal replacement by colonic interposition remains a major challenge due to its complexity and high incidence of complications; here we applied the two-stage operation strategy to oesophageal replacement by colonic interposition in high-risk oesophageal cancer patients following gastrectomy. METHODS: We performed a retrospective analysis on the data of patients with a history of distal gastrectomy who underwent one-stage and two-stage oesophageal replacement by colonic interposition from February 2012 to February 2020, and explored the relationship between the staging strategy and postoperative outcomes. RESULTS: The clinical data of 93 patients were collected and analysed. There were no significant differences in the patients' characteristics between the two groups (all p > 0.05), except for comorbidities and Charlson Comorbidity Index (all p < 0.05). The Clavien-Dindo score between the two groups was also not significantly different (p > 0.05). The logistic regression models revealed that patients who had received preoperative therapy had a higher Clavien-Dindo score (p < 0.05), but the stage strategy did not (p > 0.05). CONCLUSIONS: The two-stage operation is feasible in high-risk patients who need to undergo colonic interposition for oesophageal replacement. At the same time, it lowers the technical threshold of colonic interposition for oesophageal replacement, increasing this surgical technique's acceptability.

Relationship Between Length and Curvature of Ascending Aorta and Type a Dissection.

Background: Type A aortic dissection (TAAD) has a rapid onset and high mortality. Currently, aortic diameter is the major criterion for evaluating the risk of TAAD. We attempted to find other aortic morphological indicators to further analyze their relationships with the risk of type A dissection. Methods: We included the imaging and clinical data of 112 patients. The patients were divided into three groups, of which Group 1 had 49 patients with normal aortic diameter, Group 2 had 22 patients with ascending aortic aneurysm, and Group 3 had 41 patients with TAAD. We used AW Server software, version 3.2, to measure aorta-related morphological indicators. Results: First, in Group 1, the univariate analysis results showed that ascending aortic diameter was correlated with patient age (r 2 = 0.35) and ascending aortic length (AAL) (r 2 = 0.43). AAL was correlated with age (r 2 = 0.12) and height (r 2 = 0.11). Further analysis of the aortic morphological indicators among the three groups found that the median aortic diameter was 36.20 mm in Group 1 (Q1-Q3: 33.40-37.70 mm), 42.5 mm in Group 2 (Q1-Q3: 41.52-44.17 mm) and 48.6 mm in Group 3 (Q1-Q3: 42.4-55.3 mm). There was no significant difference between Groups 2 and 3 (P > 0.05). Group 3 had the longest AAL (median: 109.4 mm, Q1-Q3: 118.3-105.3 mm), followed by Group 2 (median: 91.0 mm, Q1-Q3: 95.97-84.12 mm) and Group 1 (81.20 mm, Q1-Q3: 76.90-86.20 mm), and there were statistically significant differences among the three groups (P < 0.05). The Aortic Bending Index (ABI) was 14.95 mm/cm in Group 3 (Q1-Q3: 14.42-15.78 mm/cm), 13.80 mm/cm in Group 2 (Q1-Q3: 13.42-14.42 mm/cm), and 13.29 mm/cm in Group 1 (Q1-Q3: 12.71-13.78 mm/cm), and the difference was statistically significant in comparisons between any two groups (P < 0.05). Regression analysis showed that aortic diameter + AAL + ABI differentiated Group 2 and Group 3 with statistical significance (area under the curve (AUC) = 0.834), which was better than aortic diameter alone (AUC = 0.657; P < 0.05). Conclusions: We introduced the new concept of ABI, which has certain clinical significance in distinguishing patients with aortic dissection and aneurysm. Perhaps the ascending aortic diameter combined with AAL and ABI could be helpful in predicting the occurrence of TAAD.

Extracellular Circular RNAs Act as Novel First Messengers Mediating Cell Cross-Talk in Ischemic Cardiac Injury and Myocardial Remodeling.

Myocardial infarction (MI) causes most of the mortality worldwide. Coronary obstruction-caused myocardial ischemic injury leads to permanent loss of the myocardium. Subsequent compensatory myocardial remodeling and heart failure would result in arrhythmia and even sudden death. The molecular mechanisms of these pathological processes remain to be thoroughly revealed. Circular RNAs (circRNAs) are special types of non-coding RNAs which can durably regulate gene expression and modulate cell fate. They had been reported to mediate ischemic myocardial injury and myocardial remodeling. circRNAs can be loaded into extracellular vesicles and released into extracellular space. More recently, it was uncovered that the extracellular circRNAs can regulate intercellular communications, similar to "first messengers." The cross-talk mediated by extracellular circRNAs had been demonstrated to play important roles in pathological processes. Here, we would like to review the modulation of extracellular circRNAs in ischemic myocardial injury and myocardial remodeling. We believe the extracellular circRNAs can bring new strategies of MI treatment.

Upregulation of long non-coding RNA myocardial infarction-associated transcription is correlated with coronary artery stenosis and elevated inflammation in patients with coronary atherosclerotic heart disease.

Coronary atherosclerotic heart disease (CAD) is a chronic disease caused by multiple risk factors. Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as an independent risk factor of CAD. This study evaluated lncRNA myocardial infarction-associated transcription (MIAT) expression in CAD patients and its clinical significance. Totally, 155 CAD patients and 76 non-CAD controls were enrolled. MIAT expression was detected using reverse transcription quantitative polymerase chain reaction. The clinical diagnostic significance of MIAT was evaluated by plotting the receiver operating characteristic (ROC) curve. The levels of inflammatory cytokines were detected using enzyme-linked immunosorbent assay. microRNA (miR)-29b-3p expression and pregnancy-associated plasma protein A (PAPPA) level were detected. MIAT expression in CAD patients (4.23 [1.22-6.50]) was higher than that in non-CAD controls (1.64 [0.05-2.93]) (p < 0.01) and had an independent correlation with CAD. The area under ROC curve of predicting CAD was calculated as 0.790, the specificity as 71.40%, and the sensitivity as 70.00%. MIAT expression was positively correlated with the C-reactive protein level (r = 0.769, p < 0.0001) and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-8 levels, while negatively correlated with the anti-inflammatory cytokine IL-10. MIAT was positively correlated with Gensini score and had an independent correlation with it. LncRNA MIAT sponged miR-29b-3p and miR-29b-3p targeted PAPPA. In conclusion, lncRNA MIAT was upregulated in the peripheral blood of CAD patients and elicited clinical diagnostic significance. MIAT participated in the development of CAD via miR-29b-3p/PAPPA axis. This study provides insights into a potential target for the diagnosis and treatment of CAD.

Modified 2-cm super single port vs. the traditional 3-cm single port for video-assisted thoracoscopic surgery lobectomy.

PURPOSES: We introduce a novel 2-cm single port designed to minimize intercostal muscle and nerve damage in video-assisted thoracoscopic surgery (VATS) lobectomy, and compared it with the 3-cm traditional single port. METHODS: We analyzed, retrospectively, the clinical data, safety, convenience, incision complications, and postoperative pain and numbness in 81 patients who underwent either modified (n = 42) or traditional (n = 39) single-port VATS lobectomy. RESULTS: The preoperative variables were comparable between both single-port VATS lobectomy groups after matching. There were no serious complications and there was no mortality in either group. There were no remarkable differences between the groups in intraoperative blood loss, chest tube duration, lymph node dissection, or postoperative complications. The modified single-port group had a longer operation time (p < 0.05), but the static and dynamic postoperative VAS scores and incisional numbness were better in the modified single-port group (p < 0.05). The modified single-port group also had an obvious advantage in incision seepage, healing, and appearance. CONCLUSIONS: Our 2-cm modified single port for lobectomy is safe and effective, and results in less postoperative pain and incisional numbness than the 3-cm traditional single port.

Effect of cardiopulmonary bypass reoxygenation on myocardial dysfunction following pediatric tetralogy of Fallot repair.

BACKGROUND: Little is known regarding the effect of cardiopulmonary bypass (CPB) reoxygenation on cardiac function following tetralogy of Fallot repair. We hypothesized that hyperoxic reoxygenation would be more strongly associated with myocardial dysfunction in children with tetralogy of Fallot. METHODS: We investigated the association of perfusate oxygenation (PpO2) associated with myocardial dysfunction among children aged 6-72 months who underwent complete repair of tetralogy of Fallot in 2012-2018. Patients were divided into two groups: lower PpO2 group (≤ 250 mmHg) and higher PpO2 (> 250 mmHg) group based on the highest value of PpO2 during aortic occlusion. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. RESULTS: This study included 163 patients perfused with lower PpO2 and 213 with higher PpO2, with median age at surgery 23.3 (interquartile range [IQR] 12.5-39.4) months, 164 female (43.6%), and median body mass index 15.59 (IQR 14.3-16.9) kg/m2. After adjustment for baseline, clinical and procedural variables, patients with higher PpO2 were associated with higher risk of myocardial dysfunction than those with lower PpO2 (OR 1.770; 95% CI 1.040-3.012, P = 0.035). Higher PpO2, lower SpO2, lower pulmonary annular Z-score, and longer CPB time were independent risk factors for myocardial dysfunction. CONCLUSIONS: Association exists between higher PpO2 and myocardial dysfunction risk in patients with tetralogy of Fallot, highlighting the modulation of reoxygenation during aortic occlusion to reduce cardiovascular damage following tetralogy of Fallot repair. TRIAL REGISTRATION: Clinical Trials. gov number NCT03568357. June 26, 2018.

LDH, CRP and ALB predict nucleic acid turn negative within 14 days in symptomatic patients with COVID-19.

AIMS: To search for biochemical indicators that can identify symptomatic patients with COVID-19 whose nucleic acid could turn negative within 14 days, and assess the prognostic value of these biochemical indicators in patients with COVID-19. PATIENTS AND METHODS: We collected the clinical data of patients with COVID-19 admitted to our hospital, by using logistic regression analysis and AUC curves, explored the relationship between biochemical indicators and nucleic acid positive duration, the severity of COVID-19, and hospital stay respectively. RESULTS: A total of two hundred and thirty-three patients with COVID-19 were enrolled in the study. We found patients whose nucleic acid turned negative within 14 days had lower LDH, CRP and higher ALB (P < 0.05). ROC curve results indicated that lower LDH, TP, CRP and higher ALB predicted the nucleic acid of patients turned negative within 14 days with statistical significance(P < 0.05), AST, LDH, CRP and PCT predicted the severe COVID-19 with statistical significance, and CRP predicted hospital stay >31days with statistical significance (P < 0.05). After verification, the probability of nucleic acid turning negative within 14 days in patients with low LDH (<256 U/L), CRP (<44.5 mg/L) and high ALB (>35.8 g/L) was about 4 times higher than that in patients with high LDH, CRP and low ALB (P < 0.05). CONCLUSIONS: LDH, CRP and ALB are useful prognostic marker for predicting nucleic acid turn negative within 14 days in symptomatic patients with COVID-19.

The growing landscape of succinylation links metabolism and heart disease.

Post-translational modification of proteins is an important biochemical process that occurs at the protein level. Succinylation is a newly discovered post-translational modification with the hallmark of a significant chemical and structural change. Succinylation has many similarities with other modifications, but succinylation may lead to more functional changes. Although the physiological significance of succinylation has not been well characterized, the lysine succinylation modification shows great potentials during disease processes. The discovery of SIRT5 has made great progress in exploring the role of succinylation in energy metabolism, heart disease and tumorigenesis. In this review, we focus on the discovery of succinylation in organisms and mechanism of succinylation. We are also concerned with the metabolic reactions and heart diseases associated with succinylation.

Modified left subsuperior segmentectomy via 2-cm uniportal video-assisted thoracoscopic surgery.

Independent subsuperior segmentectomy (S*) via uniportal video-assisted thoracoscopic surgery (VATS) has rarely been reported. We describe our modified technique of performing simplified left subsuperior segmentectomy for a lung nodule, via 2-cm uniportal VATS. The uniportal approach was different from the traditional approach made by blunt separation into the thorax without electrocautery. Our modified technique minimizes damage to the intercostal nerves and muscles. We also simplified the subsuperior segmentectomy procedure according to the findings of three-dimensional (3D) computed tomography angiography and bronchography. Combining these two techniques achieves a new more minimally invasive method for subsuperior segmentectomy.

Reconstruction of the esophagus of patients with middle thoracic esophageal carcinoma using the remnant stomach following Billroth II gastrectomy.

It seems impossible to reconstruct the esophagus of patients with middle thoracic esophageal carcinoma with a history of distal gastrectomy using the remnant stomach. Although surgeons have made multiple efforts to reconstruct the esophagus using the remnant stomach, it can only be successfully used in cases of lower thoracic esophageal cancer. Additionally, the surgery is more complex than traditional esophagogastrostomy due to challenges including mobilization of the remnant stomach with the spleen and transposition of the pancreatic tail into the left hemithorax. Our operation proved that the remnant stomach, which we named as the completely mobilized remnant stomach after dissection of the feeding vessels, remained viable. We successfully integrated the completely mobilized remnant stomach in the reconstruction of the lower thoracic esophageal tract and then integrated it in Ivor Lewis esophagogastrostomy. We describe this new alternative surgical technique for the treatment of middle thoracic esophageal carcinoma in patients with a history of distal gastrectomy in this study. Clinical data of 23 patients from 2008 to 2019 were retrospectively analyzed. All patients underwent the Ivor Lewis procedure. All remaining vessels of the remnant stomach were dissected at their origins, and Roux-en-Y reconstruction or Braun anastomosis was performed. After esophagectomy during right thoracotomy, anastomosis of the remnant stomach and esophagus was performed. Two-field lymph node dissections were performed. There was no case of necrosis of the remnant stomach or of perioperative death. Serious complications included anastomotic leak in three cases, afferent-efferent loop syndrome in one, and anastomotic stricture in two. Application of the completely mobilized remnant stomach in Ivor Lewis esophagogastrostomy is feasible, and the surgical procedure is similar to that of normal esophagogastrostomy.

Baicalein attenuates cardiac hypertrophy in mice via suppressing oxidative stress and activating autophagy in cardiomyocytes.

Baicalein is a natural flavonoid extracted from the root of Scutellaria baicalensis that exhibits a variety of pharmacological activities. In this study, we investigated the molecular mechanisms underlying the protective effect of baicalein against cardiac hypertrophy in vivo and in vitro. Cardiac hypertrophy was induced in mice by injection of isoproterenol (ISO, 30 mg·kg-1·d-1) for 15 days. The mice received caudal vein injection of baicalein (25 mg/kg) on 3rd, 6th, 9th, 12th, and 15th days. We showed that baicalein administration significantly attenuated ISO-induced cardiac hypertrophy and restored cardiac function. The protective effect of baicalein against cardiac hypertrophy was also observed in neonatal rat cardiomyocytes treated with ISO (10 µM). In cardiomyocytes, ISO treatment markedly increased reactive oxygen species (ROS) and inhibited autophagy, which were greatly alleviated by pretreatment with baicalein (30 µM). We found that baicalein pretreatment increased the expression of catalase and the mitophagy receptor FUN14 domain containing 1 (FUNDC1) to clear ROS and promote autophagy, thus attenuated ISO-induced cardiac hypertrophy. Furthermore, we revealed that baicalein bound to the transcription factor FOXO3a directly, promoting its transcription activity, and transactivated catalase and FUNDC1. In summary, our data provide new evidence for baicalein and FOXO3a in the regulation of ISO-induced cardiac hypertrophy. Baicalein has great potential for the treatment of cardiac hypertrophy.

Reversible N6-methyladenosine of RNA: The regulatory mechanisms on gene expression and implications in physiology and pathology.

N6-methyladenosine (m6A) is the most abundant inner RNA modification in eukaryotes. Due to the development of RNA sequencing technology, the distribution pattern of m6A in the transcriptome has been uncovered. Dynamically, the reversible N6-methylation is mediated by two types of proteins, which are classified as "writers" and "erasers". Under the association of specific co-factors, writers show spatiotemporal N6-methyltransferase activity. Mechanically, m6A can be recognized by "reader" proteins or can directly modify RNA conformation, and it widely affects gene expression by mediating RNA stability, translation, splicing and export. m6A is involved in a series of physiology processes. Dysregulation of m6A is gradually defined as the pathogenesis of some diseases, e.g., cancer and cardiovascular disease. Therefore, a good understanding of m6A is essential for molecular biology and pathology research. In this article we systemically present an overview of the functions and mechanisms of identified m6A regulators. The discovered biological and pathological processes affected by m6A are also summarized. We hope that readers with related research interests benefit from our review.

MicroRNA-31-5p Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via Inactivating Cab39/AMPKα Pathway.

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPKα) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPKα to exert the protective effects that were abrogated by AMPKα inhibition. Further studies revealed that Cab39 was required for AMPKα activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPKα.