Histone deacetylase inhibitors inhibit lung adenocarcinoma metastasis via HDAC2/YY1 mediated downregulation of Cdh1.

Metastasis is a leading cause of mortality in patients with lung adenocarcinoma. Histone deacetylases have emerged as promising targets for anti-tumor drugs, with histone deacetylase inhibitors (HDACi) being an active area of research. However, the precise mechanisms by which HDACi inhibits lung cancer metastasis remain incompletely understood. In this study, we employed a range of techniques, including qPCR, immunoblotting, co-immunoprecipitation, chromatin-immunoprecipitation, and cell migration assays, in conjunction with online database analysis, to investigate the role of HDACi and HDAC2/YY1 in the process of lung adenocarcinoma migration. The present study has demonstrated that both trichostatin A (TSA) and sodium butyrate (NaBu) significantly inhibit the invasion and migration of lung cancer cells via Histone deacetylase 2 (HDAC2). Overexpression of HDAC2 promotes lung cancer cell migration, whereas shHDAC2 effectively inhibits it. Further investigation revealed that HDAC2 interacts with YY1 and deacetylates Lysine 27 and Lysine9 of Histone 3, thereby inhibiting Cdh1 transcriptional activity and promoting cell migration. These findings have shed light on a novel functional mechanism of HDAC2/YY1 in lung adenocarcinoma cell migration.

Comparison of clinical effects between regional arterial embolization combined with surgery and simple surgery in the treatment of tuberculosis-destroyed lung-a retrospective comparative cohort study.

Background: The patients with tuberculosis-destroyed lungs often have heavy adhesion in the affected side of the pleural cavity and abundant collateral circulation, which bring about considerable challenges to surgical treatment. Some patients with tuberculosis-destroyed lungs will have hemoptysis symptoms. In clinical work, we found that patients with hemoptysis before surgery due to hemoptysis through regional artery occlusion treatment often have less bleeding during surgery, and it is relatively easy to stop bleeding during surgery, and the operation time is short. This study mainly used retrospective comparative cohort studies to explore the clinical efficacy of combined surgical treatment after regional systemic artery embolization pretreatment of tuberculosis-destroyed lung and provides a basis for further optimizing the surgical treatment of tuberculosis-destroyed lung. Methods: From June 2021 to September 2022, 28 patients with tuberculosis-destroyed lungs who underwent surgery in our department from the same medical group were selected. The patients were divided into 2 groups according to whether regional arterial embolization was introduced before surgery. In the observation group (n=13), before surgery, all patients received arterial embolization in the target area for hemoptysis, and surgery was performed 24-48 h after embolization. In the control group (n=15), direct surgical treatment was performed without embolization. The factors including operation time, intraoperative blood loss, and postoperative complication rates were compared between the 2 groups to assess the value of regional artery embolization combined with surgery in the treatment of tuberculosis-destroyed lung. Results: There was no significant difference between the 2 groups in general condition and disease condition, including age, duration of disease, location of lesion, and operation method (P>0.05). The operation time in the observation group was shorter than that in the observation group (P<0.05), the amount of intraoperative bleeding in the observation group was lower than that in the control group (P<0.05). The incidence of postoperative complications including pulmonary infection, anemia, and hypoproteinemia in the observation group was lower than that in the control group (P<0.05). Conclusions: Regional arterial embolism preconditioning combined with surgical operation may reduce the risk of conventional surgical treatment, shorten the operation time, and reduce postoperative complications.

Diagnostic values of Xpert MTB/RIF, T-SPOT.TB and adenosine deaminase for HIV-negative tuberculous pericarditis in a high burden setting: a prospective observational study.

The diagnosis of tuberculous pericarditis (TBP) remains challenging. This prospective study evaluated the diagnostic value of Xpert MTB/RIF (Xpert) and T-SPOT.TB and adenosine deaminase (ADA) for TBP in a high burden setting. A total of 123 HIV-negative patients with suspected TBP were enrolled at a tertiary referral hospital in China. Pericardial fluids were collected and subjected to the three rapid tests, and the results were compared with the final confirmed diagnosis. Of 105 patients in the final analysis, 39 (37.1%) were microbiologically, histopathologically or clinically diagnosed with TBP. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) for Xpert were 66.7%, 98.5%, 96.3%, 83.3%, 44.0, 0.338, and 130.0, respectively, compared to 92.3%, 87.9%, 81.8%, 95.1%, 7.6, 0.088, and 87.0, respectively, for T-SPOT.TB, and 82.1%, 92.4%, 86.5%, 89.7%, 10.8, 0.194, and 55.8, respectively, for ADA (≥ 40 U/L). ROC curve analysis revealed a cut-off point of 48.5 spot-forming cells per million pericardial effusion mononuclear cells for T-SPOT.TB, which had a DOR value of 183.8, while a cut-off point of 41.5 U/L for ADA had a DOR value of 70.9. Xpert (Step 1: rule-in) followed by T-SPOT.TB [cut-off point] (Step 2: rule-out) showed the highest DOR value of 252.0, with only 5.7% (6/105) of patients misdiagnosed. The two-step algorithm consisting of Xpert and T-SPOT.TB could offer rapid and accurate diagnosis of TBP.

Protective effects of low-frequency magnetic fields on cardiomyocytes from ischemia reperfusion injury via ROS and NO/ONOO-.

BACKGROUND: Cardiac ischemia reperfusion (I/R) injury is associated with overproduction of reactive oxygen species (ROS). Low frequency pulse magnetic fields (LFMFs) have been reported to decrease ROS generation in endothelial cells. Whether LFMFs could assert protective effects on myocardial from I/R injury via ROS regulation remains unclear. METHODS: To simulate in vivo cardiac I/R injury, neonatal rat cardiomyocytes were subjected to hypoxia reoxygenation (H/R) with or without exposure to LFMFs. Cell viability, apoptosis index, ROS generation (including O2(-) and ONOO(-)), and NO production were measured in control, H/R, and H/R + LFMF groups, respectively. RESULTS: H/R injury resulted in cardiomyocytes apoptosis and decreased cell viability, whereas exposure to LFMFs before or after H/R injury significantly inhibited apoptosis and improved cell viability (P < 0.05). LFMFs treatment could suppress ROS (including O2(-) and ONOO(-)) generation induced by H/R injury, combined with decreased NADPH oxidase activity. In addition, LFMFs elevated NO production and enhanced NO/ONOO(-) balance in cardiomyocytes, and this protective effect was via the phosphorylation of endothelial nitric oxide synthase (eNOS). CONCLUSION: LFMFs could protect myocardium against I/R injury via regulating ROS generation and NO/ONOO(-) balance. LFMFs treatment might serve as a promising strategy for cardiac I/R injury.