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Yiming Shen,Seong Kyu Han,Pan Dong Ryu 대한수의학회 2018 Journal of Veterinary Science Vol.19 No.4
The hypothalamic paraventricular nucleus (PVN) contains two types of neurons projecting to either the rostral ventrolateral medulla (PVNRVLM) or the intermediolateral horn (IML) of the spinal cord (PVNIML). These two neuron groups are intermingled in the same subdivisions of the PVN and differentially regulate sympathetic outflow. However, electrophysiological evidence supporting such functional differences is largely lacking. Herein, we compared the electrophysiological properties of these neurons by using patch-clamp and retrograde-tracing techniques. Most neurons (>70%) in both groups spontaneously fired in the cell-attached mode. When compared to the PVNIML neurons, the PVNRVLM neurons had a lower firing rate and a more irregular firing pattern (p < 0.05). The PVNRVLM neurons showed smaller resting membrane potential, slower rise and decay times, and greater duration of spontaneous action potentials (p < 0.05). The PVNRVLM neurons received greater inhibitory synaptic inputs (frequency, p < 0.05) with a shorter rise time (p < 0.05). Taken together, the results indicate that the two pre-sympathetic neurons differ in their intrinsic and extrinsic electrophysiological properties, which may explain the lower firing activity of the PVNRVLM neurons. The greater inhibitory synaptic inputs to the PVNRVLM neurons also imply that these neurons have more integrative roles in regulation of sympathetic activity.
Yiming Shen,Janardhan P. Bhattarai,Soo Joung Park,Gyu Seung Lee,Pan Dong Ryu,Seong Kyu Han 대한수의학회 2018 Journal of Veterinary Science Vol.19 No.2
It has been reported that Korean red ginseng (KRG), a valuable and important traditional medicine, has varied effects on the central nervoussystem, suggesting its activities are complicated. The paraventricular nucleus (PVN) neurons of the hypothalamus has a critical role in stressresponses and hormone secretions. Although the action mechanisms of KRG on various cells and systems have been reported, the directmembrane effects of KRG on PVN neurons have not been fully described. In this study, the direct membrane effects of KRG on PVN neuronalactivity were investigated by using a perforated patch-clamp in ICR mice. In gramicidin perforated patch-clamp mode, KRG extract (KRGE)induced repeatable depolarization followed by hyperpolarization of PVN neurons. The KRGE-induced responses were concentrationdependentand persisted in the presence of tetrodotoxin, a voltage sensitive Na+ channel blocker. The KRGE-induced responses weresuppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM), a non–N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, but notby picrotoxin, a type A gamma-aminobutyric acid receptor antagonist. The results indicate that KRG activates non-NMDA glutamate receptorsof PVN neurons in mice, suggesting that KRG may be a candidate for use in regulation of stress responses by controlling autonomic nervoussystem and hormone secretion.
Adrenergic Control of Primo Tissue Size in Rats
Yiming Shen,Yu Jeong Kim,Pan Dong Ryu 사단법인약침학회 2022 Journal of Acupuncture & Meridian Studies Vol.15 No.1
Background: Hyperplastic morphological changes associated with erythropoiesis have been reported in the primo vascular system (PVS) tissue on the surface of abdominal organs in rats with heart failure (HF) or hemolytic anemia (HA). Objectives: Since adrenergic activity is commonly activated in both HF and HA, we investigated whether adrenergic signaling mediates the abovementioned morphological changes. Methods: We compared the effects of adrenolytic treatments (exercise training and 6-hydroxydopamine) on the gross morphology of the PVS tissues isolated from organ surfaces in HF or HA rats. HF and HA were induced by ligating the left coronary artery and injecting phenylhydrazine, respectively. We further compared the effects of norepinephrine and norepinephrine plus α- or β-adrenoceptor blockers. Results: The number of samples per rat, PN size, and proportion of red-colored samples in the PVS tissue increased in the HF and HA rats. These changes were reversed by adrenolytic treatments. Interestingly, 6-hydroxydopamine also reversed phenylhydrazineinduced hemolytic changes in erythrocytes. Subcutaneous administration of norepinephrine (3 mg/kg/d) increased the sampling frequency per rat and the PN size, but these effects were blunted at a higher dose (10 mg/kg/d). Norepinephrine administration had little effect on the proportion of red-colored tissues. Norepinephrineinduced morphological changes were completely blocked by a β-adrenoceptor antagonist (propranolol) but increased slightly by an α-adrenoceptor antagonist (phentolamine). Conclusion: Adrenergic signaling controls hyperplastic changes in the organ surface PVS in rats. These findings may explain the morphological dynamics of the PVS tissues proposed by Bong Han Kim and further clarify the pathophysiological roles of the PVS.
Xiaochen Fei,Xinxing Du,Yiming Gong,Jiazhou Liu,Liancheng Fan,Jiayi Wang,Yanqing Wang,Yinjie Zhu,Jiahua Pan,Baijun Dong,Wei Xue 대한암학회 2023 Cancer Research and Treatment Vol.55 No.3
Purpose In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence.Materials and Methods This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression.Results Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in <i>NCOR2</i>, followed by <i>BRCA2</i> (3.7%), <i>ATR</i> (2.5%), and <i>CDK12</i> (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence.Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.
Chae Jeong Lim,Yiming Shen,최민철,Pan Dong Ryu 사단법인약침학회 2020 Journal of Acupuncture & Meridian Studies Vol.13 No.4
Background: The primo vascular system (PVS) is a novel network composed of primo nodes (PNs) and primo vessels (PVs). Currently, its anatomy is not fully understood. Objectives: The aim of this study was to elucidate the three-dimensional PNePV structure. Methods: Organ-surface PVS tissue was isolated from healthy and anemic rats. The tissues were analyzed by X-ray microcomputed tomography (CT), hematoxylin and eosin staining, and scanning electron microscopy. Results: From CT images, we identified one or more bundles in a PV. In the PN, the bundles were enlarged and existed in isolation and/or in anastomosis. The transverse CT images revealed four areas of distinct intensities: zero, low, intermediate, and high. The first two were considered to be the sinuses and the subvessels of the PVS and were identified in the hematoxylin and eosinestained PN sections. The enlargement of the PN from anemic rats was associated with an increase in the intermediate-intensity area. The high-intensity area demarcated the bundle and was overlapped with the mesothelial cells. In scanning electron microscopy, the PV bundles branched out, tapering down to a single bundle at some distance from the PN. Each bundle was composed of several subvessels (~5 mm). Clustered round microcells (1e25 mm), scattered flat oval cells (~15 mm), and amorphous extracellular matrix were observed on the surface of the PVS tissue. Conclusions: The results newly showed that the primo bundle is a structural unit of both PVs and PNs. A bundle was demarcated by high CT intensity and mesothelial cells and consisted of multiple subvessels. The PN bundles contained also sinuses.