BRD3308 suppresses macrophage oxidative stress and pyroptosis via upregulating acetylation of H3K27 in sepsis-induced acute lung injury.

Background: Sepsis-induced acute lung injury (ALI) leads to severe hypoxemia and respiratory failure, contributing to poor prognosis in septic patients. Endotoxin dissemination triggers oxidative stress and the release of inflammatory cytokines in macrophages, initiating diffuse alveolar damage. The role of epigenetic histone modifications in organ injury is increasingly recognized. The present study aimed to investigate the use of a histone modification inhibitor to alleviate sepsis-induced ALI, revealing a new strategy for improving sepsis patient survival. Methods: In vivo models of ALI were established through the intraperitoneal injection of lipopolysaccharide and cecal ligation and puncture surgery. Furthermore, the disease process was simulated in vitro by stimulating Tamm-Horsfall protein-1 (THP-1) cells with lipopolysaccharide. Hematoxylin and eosin staining, blood gas analysis and pulmonary function tests were utilized to assess the extent of lung tissue damage. Western blot analysis, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence were used to measure the levels and distribution of the indicated indicators within cells and tissues. Reactive oxygen species and autophagic flux alterations were detected using specific probes. Results: BRD3308, which is a inhibitor of histone deacetylase 3, improved lung tissue damage, inflammatory infiltration and edema in ALI by inhibiting Nod-like receptor protein3-mediated pyroptosis in macrophages. By upregulating autophagy, BRD3308 improved the disruption of redox balance in macrophages and reduced the accumulation of reactive oxygen species. Mechanistically, BRD3308 inhibited histone deacetylase 3 activity by binding to it and altering its conformation. Following histone deacetylase 3 inhibition, acetylation of H3K27 was significantly increased. Moreover, the increase in H3K27Ac led to the upregulation of autophagy-related gene 5, a key component of autophagosomes, thereby activating autophagy. Conclusions: BRD3308 inhibits oxidative stress and pyroptosis in macrophages by modulating histone acetylation, thereby preventing sepsis-induced ALI. The present study provides a potential strategy and theoretical basis for the clinical treatment of sepsis-induced ALI.

Effects of spinal cord injury associated exosomes delivered tRF-41 on the progression of spinal cord injury progression.

BACKGROUND: Spinal cord injury (SCI) is a devastating neurological and pathological condition. Exosomal tsRNAs have reported to be promising biomarkers for cancer diagnosis and therapy. This study aimed to investigate the roles of SCI-associated exosomes, and related tsRNA mechanisms in SCI. METHODS: The serum of healthy controls and SCI patients at the acute stage were collected for exosomes isolation, and the two different exosomes were used to treat human astrocytes (HA). The cell viability, apoptosis, and cycle were determined, and the expression of the related proteins were detected by western blot. Then, the two different exosomes were sent for tsRNA sequencing, and four significant known differentially expressed tsRNAs (DE-tsRNAs) were selected for RT-qPCR validation. Finally, tRT-41 was chosen to further explore its roles and related mechanisms in SCI. RESULTS: After sequencing, 21 DE-tsRNAs were identified, which were significantly enriched in pathways of Apelin, AMPK, Hippo, MAPK, Ras, calcium, PI3K-Akt, and Rap1. RT-qPCR showed that tRF-41 had higher levels in the SCI-associated exosomes. Compared with the control HA, healthy exosomes did not significantly affect the growth of HA cells, but SCI-associated exosomes inhibited viability of HA cells, while promoted their apoptosis and increased the HA cells in G2/M phase; but tRF-41 inhibitor reversed the actions of SCI-associated exosomes. Additionally, SCI-associated exosomes, similar with tRF-41 mimics, down-regulated IGF-1, NGF, Wnt3a, and ß-catenin, while up-regulated IL-1ß and IL-6; but tRF-41 inhibitor had the opposite actions, and reversed the effects induced by SCI-associated exosomes. CONCLUSIONS: SCI-associated exosomes delivered tRF-41 may inhibit the growth of HA through regulating Wnt/ ß-catenin pathway and inflammation response, thereby facilitating the progression of SCI.

Application and challenges of a metaverse in medicine.

Metaverse has been confirmed as a relatively amorphous concept of innovation, which refers to technological advancement. Metaverse, i.e., a coalition between reality world and virtual world, has created significant significance and convenience in education, communication, economy, etc. The COVID-19 outbreak has stimulated the growth of metaverse applications in medicine. The above-mentioned technology has broad applications while comprising online remote medical treatment, online conferences, medical education, preparation of surgical plans, etc. Moreover, technical, security, and financial challenges should be tackled down by the future widespread use of metaverse. Metaverse is limitlessly promising, and it will exert a certain effect on future scientific and technological advancements in the medical industry. The review article primarily aims to summarize the application of the metaverse in medicine and their challenge in the future of medicine.

Case report: Lung transplantation for treatment of paraquat intoxication: timing of transplantation.

Objective: To analyze the optimal timing of lung transplantation and summarize postoperative complications and their management after paraquat poisoning. Methods: Here, we present the clinical course of a 17-year-old boy with paraquat poisoning, in whom bilateral lung transplantation (LT) was performed. We reviewed the eight previously published articles relevant to LT after paraquat poisoning to summarize the therapeutic strategy. Results: A 17-year-old boy was admitted to the hospital after ingestion of 30-50 mL 25% paraquat. Mechanical ventilation was initiated on the 25th day after intoxication. Venovenous extracorporeal membrane oxygenation was initiated on the 26th day. Sequential bilateral LT was performed on the 27th day. Several complex postoperative complications occurred and the patient was discharged on the 50th day postoperatively. Eight case reports were included in the literature review, including 11 patients with paraquat poisoning undergoing LT. Three patients died due to paraquat poisoning leading to fibrosis in the transplanted lungs or postoperative complications. Eight patients survived during follow-up. Conclusion: LT after herbicide poisoning should be planned when hepatorenal function starts to recover, and waiting for complete recovery is unnecessary. Prevention of infection before surgery is important to reduce the incidence of postoperative infection. Complex perioperative complications caused by the herbicide itself or the late timing of transplantation can be successfully managed by a multidisciplinary team.

Analysis of pulmonary artery variation based on 3D reconstruction of CT angiography.

Objective: The aim of this study is to acquire pulmonary CT (Computed tomography) angiographic data for the purpose of creating a three-dimensional reconstruction. Additionally, we aim to analyze the features and deviations of the branches in both pulmonary lobes. This information is intended to serve as a more comprehensive and detailed reference for medical professionals when conducting preoperative evaluations and devising surgical plans. Method: Between August 2019 and December 2021, 420 patients were selected from the thoracic surgery department at the First Hospital of Jilin University, and underwent pulmonary 64 channel contrast enhanced CT examinations (Philips ICT 256). The images were acquired at a 1.5 mm slice thickness, and the DCM files that complied with DICOM (Digital Imaging and Communications in Medicine) standards were analysed for 3D (three dimensional) reconstruction using Mimics 22.0 software. The reconstructed pulmonary artery models were assessed by attending chest surgeons and radiologists with over 10 years of clinical experience. The two-dimensional image planes, as well as the coronary and sagittal planes, were utilized to evaluate the arteries. The study analyzed the characteristics and variations of the branches and courses of pulmonary arteries in each lobe of the lungs, with the exception of the subsegmental arterial system. Two chest surgeons and two radiologists with professional titles-all of whom had over a decade of clinical experience-jointly evaluated the 3D models of the pulmonary artery and similarly assessed the characteristics and variations of the branches and courses in each lobe of the lungs. Results: Significant variations were observed in the left superior pulmonary artery across the 420 subjects studied. In the left upper lobe, the blood supply of 4 arteries accounted for 50.5% (n = 212), while the blood supply of 2 arteries in the left lower lobe was the most common, accounting for 79.5% (n = 334). The greatest variation in the right pulmonary artery was observed in the branch supply of the right upper lobe mediastinal artery. In the majority of cases (77.9%), there were two arteries present, which was the most common configuration observed accounting for 64% (n = 269). In the right inferior lobe of the lung, there were typically 2-4 arteries, with 2 arteries being the most common configuration (observed in 79% of cases, n = 332). Conclusion: The three-dimensional reconstruction of pulmonary artery CT angiography enables clear observation of the branches and distribution of the pulmonary artery while also highlighting any variations. This technique holds significant clinical value for preoperative assessments regarding lesions and blood vessels.

Combined RNAi targeting human Stat3 and ADAM9 as gene therapy for non-small cell lung cancer.

[This retracts the article DOI: 10.3892/ol.2015.4018.].

Nomogram model combined thrombelastography for venous thromboembolism risk in patients undergoing lung cancer surgery.

Background: The aim of this study was to develop a nomogram model in combination with thromboelastography (TEG) to predict the development of venous thromboembolism (VTE) after lung cancer surgery. Methods: The data of 502 patients who underwent surgical treatment for lung cancer from December 2020 to December 2022 were retrospectively analyzed. Patients were then randomized into training and validation groups. Univariate and multivariate logistic regression analyses were carried out in the training group and independent risk factors were included in the nomogram to construct risk prediction models. The predictive capability of the model was assessed by the consistency index (C-index), receiver operating characteristic curves (ROC), the calibration plot and decision curve analysis (DCA). Results: The nomogram risk prediction model comprised of the following five independent risk factors: age, operation time, forced expiratory volume in one second and postoperative TEG parameters k value(K) and reaction time(R). The nomogram model demonstrated better predictive power than the modified Caprini model, with the C-index being greater. The calibration curve verified the consistency of nomogram between the two groups. Furthermore, DCA demonstrated the clinical value and potential for practical application of the nomogram. Conclusion: This study is the first to combine TEG and clinical risk factors to construct a nomogram to predict the occurrence of VTE in patients after lung cancer surgery. This model provides a simple and user-friendly method to assess the probability of VTE in postoperative lung cancer patients, enabling clinicians to develop individualized preventive anticoagulation strategies to reduce the incidence of such complications.

FSCN1 Promotes Esophageal Carcinoma Progression Through Downregulating PTK6 via its RNA-Binding Protein Effect.

Objective: Esophageal squamous cell carcinoma (ESCC) causes many deaths worldwide every year. Fascin actin-bundling protein 1(FSCN1) has been reported to be a promoter of ESCC via its actin-binding function, however, its new role as an RNA-binding protein (RBP) has not been investigated. Here, we explored the RBP role of FSCN1 in the development of ESCC. Methods: Whole-genome expression sequencing was performed to screen for altered genes after FSCN1 knockdown. RNA immunoprecipitation was performed to determine the target mRNA of FSCN1 as an RBP. In vitro experiments with ECA-109 and KYSE-150 and ex vivo experiments in tumor-bearing mice were performed to investigate the effects of FSCN1 and Protein Tyrosine Kinase 6 (PTK6) on ESCC progression. Results: FSCN1 could downregulate mRNA and the protein level of PTK6. The binding position of PTK6 (PTK6-T2) pre-mRNA to FSCN1 was determined. PTK6-T2 blocked the binding between FSCN1 and the pre-mRNA of PTK6, and thus reversed the promotion effect of FSCN1 on ESCC tumor progression via the AKT/GSK3ß signaling pathway. Conclusion: A novel effect of FSCN1, RBP-binding with the pre-mRNA of PTK6, was confirmed to play an important role in ESCC progression. PTK6-T2, which is a specific inhibitor of FSCN1 binding to the pre-mRNA of PTK6, could impede the development of ESCC.

Nanomedicine-Based Therapeutics to Combat Acute Lung Injury.

Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) may lead to a life-threatening form of respiratory failure, resulting in high mortality of up to 30-40% in most studies. Although there have been decades of research since ALI was first described in 1967, the clinical therapeutic alternatives for ALI are still in a state of limited availability. Supportive treatment and mechanical ventilation still have priority. Despite some preclinical studies demonstrating the benefit of pharmacological interventions, none of these has been proved completely effective to date. Recent advances in nanotechnology may shed new light on the pharmacotherapy of ALI. Nanomedicine possesses targeting and synergistic therapeutic capability, thus boosting pharmaceutical efficacy and mitigating the side effects. Currently, a variety of nanomedicine with diverse frameworks and functional groups have been elaborately developed, in accordance with their lung targeting ability and the pathophysiology of ALI. The in-depth review of the current literature reveals that liposomes, polymers, inorganic materials, cell membranes, platelets, and other nanomedicine approaches have conferred attractive therapeutic benefits for ALI treatment. In this review, we explore the recent progress in the study of the nanomedicine-based therapy of ALI, presenting various nanomedical approaches, drug choices, therapeutic strategies, and outcomes, thereby providing insight into the trends.

A giant posterior mediastinal malignant peripheral nerve sheath tumor and benign neurofibroma in body surface: a case report.

BACKGROUND: Neurofibromatosis comprises neurofibromatosis type 1 (NF1) and type 2 (NF2). Major tumor type of NF1 are neurofibroma recognized as benign peripheral nerve tumor, malignant peripheral nerve sheath tumor (MPNST), and glioma. CASE PRESENTATION: We report a woman with a special condition, whose tumors in body surfaces were benign neurofibroma and tumors in posterior mediastinum are MPNST. The chest-enhanced CT suggested a round soft tissue density in posteriormediastium. The diagnosis was established by pathology and immunohistochemistry. A single-stage thoracoscopic mediastinal mass resection was performed. The whole operation went smoothly and the CT scan of lungs did not show relapse of tumor three months later. CONCLUSIONS: The appearance of neurofibroma should draw particular attention to the possibility of developing MPNST. More careful imaging examinations should be carried out, and pathological examination could diagnose it.