Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction

Lu Zhang,Fangli Liu,Xiaomin Su,Yue Li,Yining Wang,Ruonan Fang,Yingying Guo,Tongzhu Jin,Huitong Shan,Xiaoguang Zhao,Rui Yang,Hongli Shan,Haihai Liang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Pulmonary fibrosis is a progressive disease characterized by epithelial cell damage, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and lung tissue scarring. Melatonin, a hormone produced by the pineal gland, plays an important role in multiple physiological and pathological responses in organisms. However, the function of melatonin in the development of bleomycin-induced pulmonary injury is poorly understood. In the present study, we found that melatonin significantly decreased mortality and restored the function of the alveolar epithelium in bleomycin-treated mice. However, pulmonary function mainly depends on type II alveolar epithelial cells (AECIIs) and is linked to mitochondrial integrity. We also found that melatonin reduced the production of reactive oxygen species (ROS) and prevented apoptosis and senescence in AECIIs. Luzindole, a nonselective melatonin receptor antagonist, blocked the protective action of melatonin. Interestingly, we found that the expression of apelin 13 was significantly downregulated in vitro and in vivo and that this downregulation was reversed by melatonin. Furthermore, ML221, an apelin inhibitor, disrupted the beneficial effects of melatonin on alveolar epithelial cells. Taken together, these results suggest that melatonin alleviates lung injury through regulating apelin 13 to improve mitochondrial dysfunction in the process of bleomycin-induced pulmonary injury.

Development of a Love Wave Based Device for Sensing Icing Process with Fast Response

Wen Wang,Yining Yin,Yana Jia,Mengwei Liu,Yong Liang,Yufeng Zhang,Minghui Lu 대한전기학회 2020 Journal of Electrical Engineering & Technology Vol.15 No.3

This work addresses the theoretical and experimental investigations of a Love wave based device employing waveguide structure of SiO2/36° YX-LiTaO3 for sensing icing process. The mass loading efect induced by the icing process modulates the acoustic wave propagation, and corresponding changes in device frequency can be collected to evaluate the icing process. The waveguide structure confnes the acoustic wave energy into SiO2 thin-flm, which contributes well to the improvement of the mass loading sensitivity. The corresponding sensing mechanism was analyzed by solving the acoustic propagation equations in layered structure. The sensing device patterned by delay-line on 36° YX-LiTaO3 substrate with SiO2 guiding layer was photolithographically developed as the sensor element, and characterized by using the high-low temperature chamber. The icing process was simulated by dropping appropriate water on top of the device surface. Very clear and fast frequency response was observed from the proposed sensing device in the icing process, and also, the infuence of SiO2 guiding layer thickness on sensor response was also investigated.

Effects of Cesium Salts on the Electrical Conductivity of the Weakly Ionized Gas in a Hypersonic MHD Channel

Hao Li,Peng Lu,Hulin Huang,Yining Zhang,Chenyuan Liu 한국항공우주학회 2023 International Journal of Aeronautical and Space Sc Vol.24 No.5

To adequately utilize the high enthalpy of the weakly ionized gas and improve the performance of the magnetohydrodynamic generator (MHDG) in a hypersonic channel, cesium salts are homogeneously injected into the gas at the entrance of the MHD channel for elevating the gas electrical conductivity. The finite rate chemical dynamics and multi-species electrical conductivity model for seven-species (N2, O2, N, O, NO, NO+, e−) were adopted to simulate the electrical conductivity of the weakly ionized gas under different magnetic fields. The results demonstrate that the electrical conductivity of the weakly ionized gas with cesium salts is significantly higher than that without cesium salts due to two positive contributions of cesium salts, one is that a portion cesium atom ionize much more electrons, and the second is that cesium salts reduce the activation energy of N + O <-> NO + e− by 3.5 times, which accelerates the production rate of electrons. The electrical conductivity of the gas with cesium salts is decreased monotonically along the flow direction, which is contrary to the trend of that without cesium salts. The variation of the collision frequency plays a crucial role in the electrical conductivity of the gas without cesium salts, nevertheless, this effect is marginal on the gas with cesium salts. The magnetic fields have negative impacts on the electrical conductivity of the gas with/without cesium salts. Additionally, the MHDG power generation efficiency is augmented with B for the gas with cesium salts, whereas the trend is reversed for that without cesium salts.

Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat

Xianwei Li,Yuanyuan Shen,Yining Lu,Jieren Yang 대한생리학회-대한약리학회 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.5

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-β₁, α-SMA and collagen I was analyzed by immunohis-tochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-β₁, AR, α-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of α-SMA and collagen I induced by TGF-β₁, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-β₁-induced proliferation of fibroblasts, up-regulation of α-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat

Li, Xianwei,Shen, Yuanyuan,Lu, Yining,Yang, Jieren The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.5

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-${\beta}_1$, ${\alpha}$-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-${\beta}_1$, AR, ${\alpha}$-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ${\alpha}$-SMA and collagen I induced by TGF-${\beta}_1$, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-${\beta}_1$-induced proliferation of fibroblasts, up-regulation of ${\alpha}$-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

Prevalence of Decreased Myocardial Blood Flow in Symptomatic Patients with Patent Coronary Stents: Insights from Low-Dose Dynamic CT Myocardial Perfusion Imaging

Yuehua Li,Mingyuan Yuan,Mengmeng Yu,Zhigang Lu,Chengxing Shen,Yining Wang,Bin Lu,Jiayin Zhang 대한영상의학회 2019 Korean Journal of Radiology Vol.20 No.4

Objective: To study the prevalence and clinical characteristics of decreased myocardial blood flow (MBF) quantified by dynamic computed tomography (CT) myocardial perfusion imaging (MPI) in symptomatic patients without in-stent restenosis. Materials and Methods: Thirty-seven (mean age, 71.3 ± 10 years; age range, 48–88 years; 31 males, 6 females) consecutive symptomatic patients with patent coronary stents and without obstructive de novo lesions were prospectively enrolled to undergo dynamic CT-MPI using a third-generation dual-source CT scanner. The shuttle-mode acquisition technique was used to image the complete left ventricle. A bolus of contrast media (50 mL; iopromide, 370 mg iodine/mL) was injected into the antecubital vein at a rate of 6 mL/s, followed by a 40-mL saline flush. The mean MBF value and other quantitative parameters were measured for each segment of both stented-vessel territories and reference territories. The MBFratio was defined as the ratio of the mean MBF value of the whole stent-vessel territory to that of the whole reference territory. An MBFratio of 0.85 was used as the cut-off value to distinguish hypoperfused from non-hypoperfused segments. Results: A total of 629 segments of 37 patients were ultimately included for analysis. The mean effective dose of dynamic CT-MPI was 3.1 ± 1.2 mSv (range, 1.7–6.3 mSv). The mean MBF of stent-vessel territories was decreased in 19 lesions and 81 segments. Compared to stent-vessel territories without hypoperfusion, the mean MBF and myocardial blood volume were markedly lower in hypoperfused stent-vessel territories (77.5 ± 16.6 mL/100 mL/min vs. 140.4 ± 24.1 mL/100 mL/min [p < 0.001] and 6.4 ± 3.7 mL/100 mL vs. 11.5 ± 4 mL/100 mL [p < 0.001, respectively]). Myocardial hypoperfusion in stentvessel territories was present in 48.6% (18/37) of patients. None of clinical parameters differed statistically significantly between hypoperfusion and non-hypoperfusion subgroups. Conclusion: Decreased MBF is commonly present in patients who are symptomatic after percutaneous coronary intervention, despite patent stents and can be detected by dynamic CT-MPI using a low radiation dose.

Myocardial Blood Flow Quantified by Low-Dose Dynamic CT Myocardial Perfusion Imaging Is Associated with Peak Troponin Level and Impaired Left Ventricle Function in Patients with ST-Elevated Myocardial Infarction

Jingwei Pan,Mingyuan Yuan,Mengmeng Yu,Yajie Gao,Chengxing Shen,Yining Wang,Bin Lu,Jiayin Zhang 대한영상의학회 2019 Korean Journal of Radiology Vol.20 No.5

Objective: To investigate the association of myocardial blood flow (MBF) quantified by dynamic computed tomography (CT) myocardial perfusion imaging (MPI) with troponin level and left ventricle (LV) function in patients with ST-segment elevated myocardial infarction (STEMI). Materials and Methods: Thirty-five STEMI patients who successfully had undergone reperfusion treatment within 1 week of their infarction were consecutively enrolled. All patients were referred for dynamic CT-MPI. Serial high-sensitivity troponin T (hs-TnT) levels and left ventricular ejection fraction (LVEF) measured by echocardiography were recorded. Twenty-six patients with 427 segments were included for analysis. Various quantitative parameters derived from dynamic CT-MPI were analyzed to determine if there was a correlation between hs-TnT levels and LVEF on admission and again at the 6-month mark. Results: The mean radiation dose for dynamic CT-MPI was 3.2 ± 1.1 mSv. Infarcted territories had significantly lower MBF (30.5 ± 7.4 mL/min/100 mL versus 73.4 ± 8.1 mL/min/100 mL, p < 0.001) and myocardial blood volume (MBV) (2.8 ± 0.9 mL/100 mL versus 4.2 ± 1.1 mL/100 mL, p = 0.044) compared with those of reference territories. MBF showed the best correlation with the level of peak hs-TnT (r = -0.682, p < 0.001), and MBV showed a moderate correlation with the level of peak hs-TnT (r = -0.437, p = 0.026); however, the other parameters did not show any significant correlation with hs-TnT levels. As for the association with LV function, only MBF was significantly correlated with LVEF at the time of admission (r = 0.469, p = 0.016) and at 6 months (r = 0.585, p = 0.001). Conclusion: MBF quantified by dynamic CT-MPI is significantly inversely correlated with the level of peak hs-TnT. In addition, patients with lower MBF tended to have impaired LV function at the time of their admission and at 6 months.

Ginsenoside Rg1 ameliorates Alzheimer's disease pathology via restoring mitophagy

Ni Wang,Junyan Yang,Ruijun Chen,Yunyun Liu,Shunjie Liu,Yining Pan,Qingfeng Lei,Yuzhou Wang,Lu He,Youqiang Song,Zhong Li The Korean Society of Ginseng 2023 Journal of Ginseng Research Vol.47 No.3

Background: Alzheimer's disease (AD) is a common form of dementia, and impaired mitophagy is a hallmark of AD. Mitophagy is mitochondrial-specific autophagy. Ginsenosides from Ginseng involve in autophagy in cancer. Ginsenoside Rg1 (Rg1 hereafter), a single compound of Ginseng, has neuroprotective effects on AD. However, few studies have reported whether Rg1 can ameliorate AD pathology by regulating mitophagy. Methods: Human SH-SY5Y cell and a 5XFAD mouse model were used to investigate the effects of Rg1. Rg1 (1µM) was added to β-amyloid oligomer (AβO)-induced or APPswe-overexpressed cell models for 24 hours. 5XFAD mouse models were intraperitoneally injected with Rg1 (10 mg/kg/d) for 30 days. Expression levels of mitophagy-related markers were analyzed by western blot and immunofluorescent staining. Cognitive function was assessed by Morris water maze. Mitophagic events were observed using transmission electron microscopy, western blot, and immunofluorescent staining from mouse hippocampus. The activation of the PINK1/Parkin pathway was examined using an immunoprecipitation assay. Results: Rg1 could restore mitophagy and ameliorate memory deficits in the AD cellular and/or mouse model through the PINK1-Parkin pathway. Moreover, Rg1 might induce microglial phagocytosis to reduce β-amyloid (Aβ) deposits in the hippocampus of AD mice. Conclusion: Our studies demonstrate the neuroprotective mechanism of ginsenoside Rg1 in AD models. Rg1 induces PINK-Parkin mediated mitophagy and ameliorates memory deficits in 5XFAD mouse models.

Light-Chain Cardiac Amyloidosis: Cardiac Magnetic Resonance for Assessing Response to Chemotherapy

Guo Yubo,Li Xiao,Gao Yajuan,Shen Kaini,Lin Lu,Wang Jian,Cao Jian,Zhang Zhuoli,Wan Ke,Zhou Xi Yang,Chen Yucheng,Zhang Long Jiang,Li Jian,Wang Yining 대한영상의학회 2024 Korean Journal of Radiology Vol.25 No.5

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Alterations of oral microbiota in Chinese children with viral encephalitis and/or viral meningitis

Li Yijie,Liu Jing,Zhu Yimin,Peng Chunying,Dong Yao,Liu Lili,He Yining,Lu Guoping,Zheng Yingjie 한국미생물학회 2022 The journal of microbiology Vol.60 No.4

The role of oral microbiota in viral encephalitis and/or viral meningitis (VEVM) remains unclear. In this hospital-based, frequency-matched study, children with clinically diagnosed VEVM (n = 68) and those with other diseases (controls, n = 68) were recruited. Their oral swab samples were collected and the oral microbiota was profiled using 16S rRNA gene sequencing. The oral microbiota of children with VEVM exhibited different beta diversity metrics (unweighted UniFrac distance: P < 0.001, R2 = 0.025, Bray-curtis dissimilarity: P = 0.045, R2 = 0.011, and Jaccard dissimilarity: P < 0.001, R2 = 0.017) and higher relative abundances of taxa identified by Linear discriminant analysis (LDA) with effect size (Enterococcus, Pedobacter, Massilia, Prevotella_9, Psychrobacter, Butyricimonas, Bradyrhizobium, etc., LDA scores > 2.0) when compared with the control group. The higher pathway abundance of steroid hormone biosynthesis predicted by oral microbiota was suggested to be linked to VEVM (q = 0.020). Further, a model based on oral microbial traits showed good predictive performance for VEVM with an area under the receiver operating characteristic curve of 0.920 (95% confidence interval: 0.834–1.000). Similar results were also obtained between children with etiologically diagnosed VEVM (n = 43) and controls (n = 68). Our preliminary study identified VEVM-specific oral microbial traits among children, which can be effective in the diagnosis of VEVM.