The TL1A-DR3 Axis in Asthma: Membrane-Bound and Secreted TL1A Co-Determined the Development of Airway Remodeling

Zhang Jintao,Zhang Dong,Pan Yun,Liu Xiaofei,Xu Jiawei,Qiao Xinrui,Cui Wenjing,Dong Liang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.2

Purpose: Tumor necrosis factor-like ligand 1A (TL1A), especially its secreted form, has been shown to contribute to eosinophilic inflammation and mucus production, cardinal features of asthma, through its receptor, death receptor 3 (DR3). However, the role of the TL1A-DR3 axis in asthma, especially in terms of airway remodeling, has not yet been fully understood. Methods: The present study investigated the expression and secretion of TL1A in the lung and human bronchial epithelial cells. DR3 small interfering RNA (siRNA), TL1A siRNA, and truncated plasmids were used respectively to identify the function of the TL1A-DR3 axis in vitro. To further validate the roles of the TL1A-DR3 axis in asthma, we collected airway biopsies and sputa from asthmatic patients and constructed a mouse model following rTL1A administration, DR3 knockdown, and TL1A knockout, the asthma-related inflammatory response and the pathological changes in airways were analyzed using various experimental methods. Associated signaling pathways downstream of TL1A knockout in the mouse model were analyzed using RNA sequencing. Results: TL1A, especially its non-secreted form (nsTL1A) was involved in the remodeling process in asthmatics’ airways. Knockdown of TL1A or its receptor DR3 decreased the expression of fibrosis-associated protein in BEAS-2B cells. Reversely, overexpression of nsTL1A in airway epithelial cells facilitated the transforming growth factor-β-induced remodeling progress. In the asthma mouse model, activating the TL1A-DR3 axis contributes to airway inflammation, remodeling, and tissue destruction. Reciprocally, DR3 knockdown or TL1A knockout partly reverses airway remodeling in the asthma model induced by ovalbumin. Conclusions: Our results confirm differential TL1A expression (including its secreted and non-secreted form) in asthma, which modulates remodeling. The shared mechanism of action by which nsTL1A and secreted TL1A exert their effects on asthma development might be mediated via the nuclear factor-κB pathway. The TL1A-DR3 axis presents a promising therapeutic target in asthma.

Higher-order expansions of sample range from skew-normal distribution

Zhang Wenjing,Lu Yingyin 한국통계학회 2023 Journal of the Korean Statistical Society Vol.52 No.4

{X_n, n ≥ 1} is a sequence of i.i.d. random variables with common skew-normal distribution, the limiting distribution of normalized sample range M_n − m_n was established in this paper, where M_n and m_n are the partial maximum and minimum of {X_n, n ≥ 1}, respectively. Meanwhile, higher-order expansions of sample range distribution and the rates of convergence to the limits are derived with optimal normalizing constants. Numerical analysis is given to compare the accuracy of the actual values with their asymptotics and illustrate the theoretical findings.

Occurrence assessment of earth fissure based on genetic algorithms and artificial neural networks in Su-Xi-Chang land subsidence area, China

Wenjing Zhang,Li Gao,Xun Jiao,Jun Yu,Xiaosi Su,Shanghai Du 한국지질과학협의회 2014 Geosciences Journal Vol.18 No.4

Earth fissures in Su-Xi-Chang land subsidence areahave induced massive damages to the area. The non-linear characteristicassociated with the process of earth fissure formation requiresnon-linear method for evaluating the occurrence of the hazard. Based on quantification of influence factors on breeding the hazard,GA-ANN method, which integrates artificial neural networks(ANN) with genetic algorithms (GA), is developed for evaluating theoccurrence of earth fissure hazard. Six indicators, that include thedepth of bedrock burial (DBB), the degree of bedrock relief (DBR),water level (WL) (the II confined aquifer), the gradient of landsubsidence (GLS), transmissivity (T) (the II confined aquifer) andthe thickness of clay soil (TCS), are selected as the input patternsof the integrated approach, and danger index (DI) as the outputpattern. A multilayer back-propagation neural network is trainedwith 30 sets of data samples including 15 sets of earth fissure samplesand 15 sets of safety samples for defining the architecture ofANN. Subsequently, GA is employed by optimizing the initial weightsof trained ANN by minimizing the deviation of output. The efficacy ofthe integrated approach is demonstrated by comparing the deviationof output from ANN and GA-ANN for 5 testing samples andthe result shows that the GA-ANN method is more accurate thanANN in identifying the occurrence of earth fissure. The integratedmethod is applied to the assessment of earth fissure hazard in typicalregions of earth fissure. According to the classification of DI, theregions are divided into four zones ‒ danger zone, sub-danger zone,sub-safe zone and safe zone.

Selenide-linked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release for diabetic wound healing

Wenjing Li,Ying Bei,Xiangqiang Pan,Jian Zhu,Zhengbiao Zhang,Tinglin Zhang,Jieting Liu,Dan Wu,Meng Li,Yan Wu,Jie Gao 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Multifunctional hydrogels with controllable degradation and drug release have attracted extensive attention in diabetic wound healing. This study focused on the acceleration of diabetic wound healing with selenidelinked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release. Methods Herein, selenium-containing hybrid hydrogels, defined as DSeP@PB, were fabricated via the reinforcement of selenol-end capping polyethylene glycol (PEG) hydrogels by polydopamine nanoparticles (PDANPs) and Prussian blue nanozymes in a one-pot approach in the absence of any other chemical additive or organic solvent based on diselenide and selenide bonding-guided crosslinking, making them accessible for large-scale mass production. Results Reinforcement by PDANPs greatly increases the mechanical properties of the hydrogels, realizing excellent injectability and flexible mechanical properties for DSeP@PB. Dynamic diselenide introduction endowed the hydrogels with on-demand degradation under reducing or oxidizing conditions and light-triggered nanozyme release. The bioactivity of Prussian blue nanozymes afforded the hydrogels with efficient antibacterial, ROS-scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further animal studies indicated that DSeP@PB under red light irradiation showed the most efficient wound healing activity by stimulating angiogenesis and collagen deposition and inhibiting inflammation. Conclusion The combined merits of DSeP@PB (on-demand degradation, light-triggered release, flexible mechanical robustness, antibacterial, ROS-scavenging and immunomodulatory capacities) enable its high potential as a new hydrogel dressing that can be harnessed for safe and efficient therapeutics for diabetic wound healing.

Tensile-Mechanical Degradation-Properties and J-C Constitutive Model of Studs after Strong-Acid Corrosion

Wenjing Qiao,Hao Zhang,Gang Zhang,Fan Yang,Zhiguo Liu 대한토목학회 2022 KSCE Journal of Civil Engineering Vol.26 No.9

This paper presents an investigation on strong-acid relations between corrosion rate and corrosion time in 30 studs, dipped into 36% industrial hydrochloric acid through 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h, respectively. These corroded studs are performed tensile tests to study failure mode and stress-strain curves in studs with different corrosion time. Thereafter, a 3-D finite element is established through computer program to validate test results, and then analyze mechanical properties along with failure mode of studs exposed to strong-acid corrosion. The analysis results show that the failure mode gradually changes from ductile-damage state to brittle-damage state. The corrosion rates present a non-linear elevation with an increase of strong-acid-corrosion time. The nominal yield strength, the nominal ultimate strength, and the elongation in the corroded studs exhibit a fast-downward trend when increasing corrosion time. However, the degradation of elastic modulus turn into a slow step and the yield strength ratio in studs tends to be steady. The J-C model (Johnson-Cook Constitutive) with updated coefficients can be applied to reflect the constitutive relations in studs after strong-acid corrosion under quasi-static tension conditions. Further, this model can simulate stress flows within studs after strong-acid corrosion. This research results can provide a guide for long-lifetime construction and safe maintenance in steel structural bridge.

ROCK1 induces dopaminergic nerve cell apoptosis via the activation of Drp1-mediated aberrant mitochondrial fission in Parkinson’s disease

Qian Zhang,Changpeng Hu,Jingbin Huang,Wuyi Liu,Wenjing Lai,Faning Leng,Qin Tang,Yali Liu,Qing Wang,Min Zhou,Fangfang Sheng,Guobing Li,Rong Zhang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Dopamine deficiency is mainly caused by apoptosis of dopaminergic nerve cells in the substantia nigra of themidbrain and the striatum and is an important pathologic basis of Parkinson’s disease (PD). Recent research has shownthat dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays a crucial role in dopaminergicnerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study showed that Drp1knockdown inhibited aberrant mitochondrial fission and apoptosis. Importantly, we found that ROCK1 was activated inan MPP+-induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cells by suppressing Drp1dephosphorylation/activation. Our in vivo study confirmed that Y-27632 significantly improved symptoms in a PDmouse model by inhibiting Drp1-mediated aberrant mitochondrial fission and apoptosis. Collectively, our findingssuggest an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cellapoptosis via the activation of Drp1-induced aberrant mitochondrial fission.

Molecular and phylogenetic analysis of Anaplasma spp. in sheep and goats from six provinces of China

Yan Zhang,Yali Lv,Feifei Zhang,Wenjing Zhang,Jinhong Wang,Yanyan Cui,Rongjun Wang,Fuchun Jian,Longxian Zhang,Changshen Ning 대한수의학회 2016 Journal of Veterinary Science Vol.17 No.4

Members of the genus Anaplasma are important emerging tick-borne pathogens in both humans and animals in tropical and subtropical areas. Here, we investigated the presence of Anaplasma spp. in 621 sheep and 710 goats from six provinces of China. Polymerase chain reaction(PCR) and DNA sequencing were conducted to determine the prevalence of Anaplasma (A.) phagocytophilum, A. ovis and A. bovis targetingthe 16S ribosomal RNA or the major surface protein 4 gene. PCR revealed Anaplasma in 39.0% (240/621) of sheep and 45.5% (323/710)of goats. The most frequently detected species was A. ovis (88/621, 14.2% for sheep; 129/710, 18.2% for goats), followed by A. bovis (60/621,9.7% for sheep; 74/710, 10.4% for goats) and A. phagocytophilum (33/621, 5.3% for sheep; 15/710, 2.1% for goats). Additionally, eight sheepand 20 goats were found to be infected with three pathogens simultaneously. DNA sequencing confirmed the presence of these three Anaplasmaspecies in the investigated areas, and phylogenetic analysis indicated that there was geographic segregation to a certain extent, as well as arelationship between the host and cluster of A. ovis. The results of the present study provide valuable data that helps understand theepidemiology of anaplasmosis in ruminants from China.

Study on pharmacokinetics and tissue distribution of single dose oral tryptanthrin in Kunming mice by validated reversed-phase high-performance liquid chromatography with ultraviolet detection

Xiaoyan Zhang,Jie Xia,Wenjing Zhang,Yao Luo,Wenbo Sun,Wei Zhou 한국한의학연구원 2017 Integrative Medicine Research Vol.6 No.3

Background: Tryptanthrin is a major active constituent of several Chinese herbal plants, such as Isatidis radix. Tryptanthrin had been demonstrated to have several beneficial pharmacological effects in vitro for human diseases, including antitumor, anti-inflammatory and antibacteria activities. In contrast to the extensive in vitro investigations, the in vivo disposition process of tryptanthrin was explored limitedly. Methods: In this study, the pharmacokinetics (PK) and tissue distribution of tryptanthrin in Kunming mice following a single oral dose of 80 mg/kg tryptanthrin were investigated for the first time. Mouse plasma, liver, heart, spleen, lung, kidney and brain were collected and analyzed using a validated reversed-phase high-performance liquid chromatography with ultraviolet detection (RP-HPLC–UV) method after biological sample preparation by a simple liquid–liquid extraction. Results: The chromatographic analysis was performed on a Diamonsil C18 column (5 μm, 250 mm × 4.6 mm) and ultraviolet detection was set at a wavelength of 251 nm. The analysis was achieved with a mobile phase of methanol (A) and water (B) (60:40, v/v) at a flow rate of 1.0 mL/min. The method was linear over the concentration range of 4.0–400.0 μg/mL with a lower limit of quantification of 0.10–0.30 μg/mL. Inter- and intraday precisions (relative standard deviations %) were all within 2.93%. Recoveries of tryptanthrin were more than 86.44%. Maximal tryptanthrin concentrations in plasma and tissues of mice were reached within 2.5 hours. The actual highest concentration (Cmax) in mouse plasma was 3.13 μg/mL, the area under the curve (AUC0–t) was 9.38 h μg/mL, and the terminal half-life was 2.27 hours. The volume of distribution was 343.89 mL, the clearance rate was 204.58 mL/h, and the PK of tryptanthrin in mice after oral administration was fit to 2 compartment 1 st Order. After oral dosing of tryptanthrin to Kunming mice, the analyte was well distributed to the plasma and main tissues. Cmax was found in the liver with a mean value of 3.54 μg/g, followed by that in the kidney, lung, spleen, heart, and brain. Conclusion: In this study, a validated RP-HPLC–UV method was developed and successfully applied to PK and tissue distribution of oral tryptanthrin in mice. We confirmed that tryptanthrin was closely related and targeted to plasma, liver, kidney, and lung. These results indicate that tryptanthrin will have a good clinical application in the liver, kidney, or lung. The clinical use of tryptanthrin should focus on its pharmacodynamics and safety study in these tissues.

Expression of fox-related genes in the skin follicles of Inner Mongolia cashmere goat

Wenjing Han,Xiaoyan Li,Lele Wang,Honghao Wang,Kun Yang,Zhixin Wang,Ruijun Wang,Rui Su,Zhihong Liu,Yanhong Zhao,Yanjun Zhang,Jinquan Li 아세아·태평양축산학회 2018 Animal Bioscience Vol.31 No.3

Objective: This study investigated the expression of genes in cashmere goats at different periods of their fetal development. Methods: Bioinformatics analysis was used to evaluate data obtained by transcriptome sequencing of fetus skin samples collected from Inner Mongolia cashmere goats on days 45, 55, and 65 of fetal age. Results: We found that FoxN1, FoxE1, and FoxI3 genes of the Fox gene family were probably involved in the growth and development of the follicle and the formation of hair, which is consistent with previous findings. Real-time quantitative polymerase chain reaction detecting system and Western blot analysis were employed to study the relative differentially expressed genes FoxN1, FoxE1, and FoxI3 in the body skin of cashmere goat fetuses and adult individuals. Conclusion: This study provided new fundamental information for further investigation of the genes related to follicle development and exploration of their roles in hair follicle initiation, growth, and development.

DEVELOPMENT OF MAGNETICALLY RESPONSIVE Fe3O4@C CORE/SHELL MICROSPHERES AS POTENTIAL VECTORS FOR DRUG-DELIVERY APPLICATIONS

WENJING YUAN,LING ZHU,PING CHEN,ANJIAN XIE,HUI ZHANG,CUIPING WANG,YUHUA SHEN 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2013 NANO Vol.8 No.4

The Fe3O4@C core/shell microspheres were fabricated via a two-step process. Fe3O4 microspheres were firstly prepared, and Fe3O4@C core/shell microspheres were subsequently fabricated using glucose as a carbon source by a hydrothermal route, in which the thickness of the carbon coating was about 20 nm. The resulting products were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectra (FTIR). The Nitrogen adsorption–desorption isotherms reveal their mesoporous structure and larger BET surface area (62.3 m2g-1). The Fe3O4@C core/shell microspheres possess ferromagnetism and high saturation magnetization (39.2 emu ⋅ g-1). Bovine hemoglobin (BHb) was used as a model protein to test the adsorption and desorption properties of the Fe3O4@C core/shell microspheres. The capacity for BHb adsorption was more than 71.3 mg/g. According to the values obtained in the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay the Fe3O4@C core/shell microspheres show a low toxicity. Therefore, the prepared Fe3O4@C core/shell microspheres are of great significance for guided site-specific drug delivery.