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ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS‐induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf‐2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration‐dependent improvement in LPS‐induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf‐2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS‐induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries. [ABSTRACT FROM AUTHOR]

For nitride‐based AlGaN light‐emitting diodes, the fluctuations in the potential caused by alloy disorder can relax the compressive strain in the lower Al (higher Ga) composition sites. However, strain in the quantum wells impacts the bandgap and the transverse magnetic/transverse electric (TE) polarization ratio. Herein, the 6 × 6 k·p method combined with a 3D Poisson, drift diffusion, and localization landscape solver is used to study the changes in the polarization ratio due to random alloy fluctuations. The influence of different Al compositions in the buffer layer is studied. The results show that the TM polarization ratio with alloy fluctuations is higher than that without fluctuations. On increasing the Al composition in the buffer layer, the polarization ratio changes from 0.93 to −0.67 when the Al composition changes from 60% to 100%. [ABSTRACT FROM AUTHOR]

Objective: Safrole, also called shikimol and Sassafras, is the carcinogenic and phenylpropanoid compound extracted from Sassafras tree and anise, betel, and camphor. Moreover, a high concentration of safrole can be occur in the saliva because of betel nut or areca quid chewing which a common habit observed in Southern and Southeastern Asia. Notably, macrophages are crucial phagocytic cells of the immune system. Nonetheless, to date, no evidence has been reported regarding safrole-induced proinflammatory response and the corresponding mechanism in macrophages. Materials and Methods: In the present study, the cytokines expression, NO generation, protein phosphorylation, and expression were assessed by enzyme-linked immunosorbent assay, Griess reagent, and Western blot assay, respectively. Results: In this study, we determined that safrole induces the generation of nitric oxide and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and IL-6 in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, inhibitor of κB (IκB) degradation was caused by safrole in a concentration-dependent manner. In addition, the phosphorylation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) family, including p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was induced by safrole began to increase at 10 μM and attained a plateau at 100 μM. Conclusion: These results indicated that safrole induces the expression of proinflammatory responses in macrophages through the NF-κB/IκB pathway and its upstream factor, MAPK family phosphorylation. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Patients with chronic obstructive pulmonary disease (COPD) frequently experience concurrent comorbidities; therefore, risk assessment for major adverse cardiovascular events (MACEs) is very important. Objectives: We explored the association between COPD and risk of MACEs with three common clinical events: acute myocardial infarction (AMI), ischemic stroke (IS), and cardiovascular death (CVD). Methods: We evaluated the predictive value of the CHA2DS2‐VASc score (congestive heart failure [C], hypertension [H], age [A], diabetes [D], stroke [S], and vascular disease [VASc]) for MACEs in COPD patients. In this observational study, we retrospectively reviewed the records of 29 258 patients with COPD between 2005 and 2009 in relation to MACE risk using the CHA2DS2‐VASc score. We calculated the hazard ratios (HR) and 95% confidence intervals (CI) using a significance level of .05. Results: Patients with COPD had significantly (P < .001) increased risk of MACEs, and a high prevalence of CHA2DS2‐VASc scores ≥ 6, predicting MACEs (16.1%), AMI (3.3%), IS (8.7%), and CVD (4.0%). A good discrimination was found for MACEs, IS events, and CVD events (AUC = 0.740, 0.739, and 0.778, respectively) but poorer discrimination for AMI events (AUC = 0.697). Conclusion: Early lifestyle modifications and antithrombotic therapy may be essential for COPD patients at a high risk of MACEs, that is, those with CHA2DS2‐VASc scores ≥ 6. [ABSTRACT FROM AUTHOR]

The alkaline intracellular environment of cancer cells is critical for cell proliferation and controlled by various plasma membrane transporters including Na+/H+ exchangers (NHEs). NHEs can also mediate cell behavior by regulating signaling transduction. In this study, we investigated the role of NHE7 in cancer stem cell (CSC) activity in non-small cell lung cancer (NSCLC) cells and the potential therapeutic implications of targeting NHE7 and the associated immune checkpoint molecule PD-L1. By analyzing the database from The Cancer Genome Atlas, we found a positive correlation between SLC9A7 mRNA levels (the gene encoding NHE7) and poor overall survival in lung adenocarcinoma patients. Using 5-(N-ethyl-N-isopropyl)-Amiloride (EIPA) to inhibit NHE7 activity, we observed disrupted cell cycle progression and suppressed NSCLC cell proliferation without inducing apoptosis. Furthermore, EIPA demonstrated a suppressive effect on CSC activity, evidenced by decreased tumorsphere numbers and inhibition of CSC markers such as ALDH1A2, ABCG2, CD44, and CD133. Flow cytometric analysis revealed that EIPA treatment or NHE7 knockdown in NSCLC cells led to downregulated PD-L1 expression, associated with inhibited STAT3 activity. Interestingly, EIPA's CSC-targeting activity was preferentially observed in NSCLC cells overexpressing BMI1, while increased PD-L1 expression was detected in BMI1-overexpressing NSCLC cells. Our findings suggest that targeting NHE7 with inhibitors like EIPA may have therapeutic potential in NSCLC treatment by disrupting cell cycle progression and suppressing CSC activity. The observed increase in PD-L1 expression in BMI1-overexpressing NSCLC cells upon EIPA treatment highlights the potential benefit of combining NHE7 inhibitors with anti-PD-L1 agents as a promising new therapeutic strategy for NSCLC., Competing Interests: None., (AJCR Copyright © 2023.)