Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells

Fan Liang-Liang,Du Ran,Liu Ji-Shi,Jin Jie-Yuan,Wang Chen-Yu,Dong Yi,He Wan-Xia,Yan Ri-Qiang,Xiang Rong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has previously been shown to play roles in neurodegenerative diseases, but little is known about its function in the kidneys. The aim of the present study was to clarify the roles of RTN3 in chronic kidney disease (CKD) and kidney fibrosis. In this study, RTN3 levels were measured in kidney tissues from healthy controls and CKD or kidney fibrosis patients. An RTN3-null mouse model was generated to explore the pathophysiological roles of RTN3 in the kidneys. The underlying mechanisms were studied in primary proximal tubular epithelial cells and HEK293 cells in vitro. The results showed that (1) a reduction in RTN3 in mice induces CKD and kidney fibrosis; (2) decreased RTN3 expression is found in patients with CKD; (3) RTN3 plays critical roles in regulating collagen biosynthesis and mitochondrial function; and (4) mechanistically, RTN3 regulates these phenotypes by interacting with GC-Rich Promoter Binding Protein 1 (GPBP1), which activates the IGF2-JAK2-STAT3 pathway. Our study indicates that RTN3 might play crucial roles in CKD and kidney fibrosis and that a reduction in RTN3 in the kidneys might be a risk factor for CKD and kidney fibrosis.

Toll-Like Receptor 4 Mutation Protects Obese Mice Against Endothelial Dysfunction by Decreasing NADPH Oxidase Isoforms 1 and 4

Liang, Chao-Fan,Liu, Jacky TC,Wang, Yu,Xu, Aimin,Vanhoutte, Paul M. American Heart Association, Inc. 2013 Arteriosclerosis, thrombosis, and vascular biology Vol.33 No.4

<P><B>Objective—</B></P><P>To analyze the role of toll-like receptor 4 in modulating metabolism and endothelial function.</P><P><B>Approach and Results—</B></P><P>Type 2 diabetic mice with mutated toll-like receptor 4 (DWM) were protected from hyperglycemia and hypertension, despite an increased body weight. Isometric tension was measured in arterial rings with endothelium. Relaxations to acetylcholine were blunted in aortae and mesenteric arteries of Lepr<SUP>db/db</SUP> mice, but not in DWM mice; the endothelial NO synthase dimer/monomer ratio and endothelial NO synthase phosphorylation levels were higher in DWM preparations. These differences were abolished by apocynin. Contractions to acetylcholine (in the presence of L-NAME) were larger in carotid arteries from Lepr<SUP>db/db</SUP> mice than from DWM mice and were inhibited by indomethacin and SC560, demonstrating involvement of cyclooxygenase-1. The release of 6-ketoprostaglandin F<SUB>1α</SUB> was lower in DWM mice arteries, implying lower cyclooxygenase-1 activity. Apocynin, manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin, catalase, and diethyldithiocarbamate inhibited endothelium-dependent contractions. The mRNA and protein levels of NADPH oxidase isoforms NOX1 and NOX4 were downregulated in DWM mice arteries. The in vivo and in vitro administration of lipopolysaccharide caused endothelial dysfunction in the arteries of wild-type, but not toll-like receptor 4–mutated mice.</P><P><B>Conclusions—</B></P><P>Toll-like receptor 4 plays a key role in obesity and diabetes-associated endothelial dysfunction by increasing oxidative stress.</P>

Does H3K27M Mutation Impact Survival Outcome of High-Grade Spinal Cord Astrocytoma?

Fan Zhang,Lei Cheng,Ze Ding,Shengxi Wang,Xingang Zhao,Zijun Zhao,Cong Liang,Kun Wu,Dongao Zhang,Yinqian Wang,Tao Fan 대한척추신경외과학회 2023 Neurospine Vol.20 No.4

Objective: To evaluate the impact of H3K27M mutation in the prognosis of histological high-grade intramedullary astrocytoma. Methods: A total of 78 patients who were diagnosed with high-grade spinal cord astrocytoma were included. Clinical data consisting demographic, radiological, molecular features and treatment data were recorded. Univariate and multivariate Cox analysis were performed to investigate variables associated with survival outcome of histological high-grade spinal cord astrocytoma. Results: Median survival time was 21 months. Overall survival (OS) at 1 and 3 years was 65.7% and 40.7%, respectively. Sex, location, and tumor span did not present significant association with OS. Patients with H3K27M mutation showed significant shorter duration of symptom than patients with H3K27 wild-type. As respect to adjuvant treatment, adjuvant radiotherapy and chemotherapy were associated with favorable OS (both p = 0.01). Younger patients (age ≤ 18 years) had shorter OS (p = 0.008) than adult patients (age > 18 years). Of note, H3K27M mutation did not show significant impact on the survival outcome, regardless of histology grade 3 or grade 4 (p = 0.3). Conclusion: Histological high-grade spinal cord astrocytoma has dismal prognosis. Our study demonstrated that H3K27M mutation did not show significant impact on survival outcome of histological high-grade spinal cord astrocytoma.

IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis

Liang Li,Zhang Fengmei,Feng Naibo,Kuang Biao,Fan Mengtian,Chen Cheng,Pan Yiming,Zhou Pengfei,Geng Nana,Li Xingyue,Xian Menglin,Deng Lin,Li Xiaoli,Kuang Liang,Luo Fengtao,Tan Qiaoyan,Xie Yangli,Guo Fen 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

Temperature Distribution and Mechanical Response of Orthotropic Steel Bridge Deck During Paving of Gussasphalt Pavement

Liang Fan,Weipeng Yang,Dan Zhou,Zhengyi Li 한국강구조학회 2021 International Journal of Steel Structures Vol.21 No.1

To investigate the temporal–spatial temperature fi eld and mechanical response of an orthotropic steel bridge deck during paving with gussasphalt concrete (GAC), in situ monitoring of the Cuntan Yangtze River Bridge in China was conducted during GAC paving, and a fi nite element method model of the temperature fi eld was established. The test and model show the following: (1) The maximum temperature occur at the paving area mid-span on the steel bridge deck, and the temperature stress of the ribs is non-negligible. (2) The deck in the paving and non-paving areas is mainly subjected to compressive and tensile stresses, respectively. (3) The beam end of the steel box expanded outward, and the deck bulge upward. (4) Based on the analysis of the construction parameters, the paving temperature and width have a greater infl uence than the paving speed on the stress and deformation fi elds. In bridge design, the temperature-stress problem caused by high-temperature pavement and the pavement thickness problem caused by the temperature deformation of the deck must be considered. The longitudinal elongation should meet the allowable limits of the corresponding telescopic device. These results can provide a reference for construction workers and maintenance personnel of bridge deck pavement.

A case report of a carbon dioxide embolism caused by endoscopic vein harvesting during cardiac surgery -A case report-

Liang Fan,Dawn Denisco,David L. Knorz,Renee M. Mapes,Nader D. Nader 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.63 No.2

A carbon dioxide (CO2) embolism during endoscopic vein harvesting is a rare but potentially fatal complication. Early and accurate diagnosis is crucial for limiting the extent of the embolism and stabilizing the resulting cardiovascular compromise. We report a case of CO2 embolization during endoscopic vein harvesting. Transesophageal echocardiography was instrumental in the diagnosis and management of this patient by further improving the decision making process, which resulted in the best outcome. Mid-esophageal bicaval view is the best view to determine whether a CO2 embolism is coming from the upper or lower extremities.

INFINITELY MANY SMALL SOLUTIONS FOR THE p&q-LAPLACIAN PROBLEM WITH CRITICAL SOBOLEV AND HARDY EXPONENTS

Liang, Sihua,Zhang, Jihui,Fan, Fan The Korean Society for Computational and Applied M 2010 Journal of applied mathematics & informatics Vol.28 No.5

In this paper, we study the following p&q-Laplacian problem with critical Sobolev and Hardy exponents {$-{\Delta}_pu-{\Delta}_qu={\mu}\frac{{\mid}u{\mid}^{p^*(s)-2}u}{{\mid}x{\mid}^s}+{\lambda}f(x,\;u)$, in $\Omega$, u=0, on $\Omega$, where ${\Omega}\;{\subset}\;\mathbb{R}^{\mathbb{N}}$ is a bounded domain and ${\Delta}_ru=div({\mid}{\nabla}u{\mid}^{r-2}{\nabla}u)$ is the r-Laplacian of u. By using the variational method and concentration-compactness principle, we obtain the existence of infinitely many small solutions for above problem which are the complement of previously known results.

Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis

Dachuan Fan,Xiangdong Wang,Min Wang,Yang Wang,Liang Zhang,Ying Li,Erzhong Fan,Feifei Cao,Koen Van Crombruggen,Luo Zhang 대한천식알레르기학회 2016 Allergy, Asthma & Immunology Research Vol.8 No.3

Purpose: Group 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens. Methods: Flow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage- and Lineage+ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage- and Lineage+ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit. Results: The percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33±IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage- cells compared to Lineage+ cells. Conclusions: AR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.

Empirical likelihood inference for semiparametric model with linear process errors

Guo-Liang Fan,Han-Ying Liang 한국통계학회 2010 Journal of the Korean Statistical Society Vol.39 No.1

The purpose of this article is to use the empirical likelihood method to study the confidence regions construction for the parameters of interest in semiparametric model with linear process errors under martingale difference. It is shown that the adjusted empirical loglikelihood ratio at the true parameters is asymptotically chi-squared. A simulation study indicates that the adjusted empirical likelihood works better than a normal approximationbased approach.

Transcriptome analysis reveals molecular strategies of Bactrocera dorsalis (Hendel) larvae in response to anoxia

Deng Yufang,Jiang Fan,Hu Fan,Liang Liang,Wang Yuejin 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.4

Bactrocera dorsalis and its larvae have evolved to cope with the hypoxic environment during their lifetime. In this study, we sequenced the transcriptomes of B. dorsalis under and post anoxia stress. Our data revealed the different biological mechanisms of B. dorsalis in response to anoxia and during recovery from anoxia. The in duction of heat shock proteins (HSPs) might be one of the important mechanisms for B. dorsalis to tolerate anoxia. Furthermore, our data showed B. dorsalis acquires energy through gluconeogenesis rather than glycolysis under anoxia and upregulated its lipid metabolism post anoxia. The up-regulation of the genes involved in the Hippo signaling pathway might also play a role in eliminating damaged cells as a result of anoxia. Furthermore, the HIF system of B. dorsalis did not change in response to anoxia stress in this study. We hypothesized that the HIF system in B. dorsalis might be activated by a specific duration of anoxia.