Isoliquiritigenin attenuates spinal tuberculosis through inhibiting immune response in a New Zealand white rabbit model

Wenjing Wang,Baozhi Yang,Yong Cui,Ying Zhan 대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.4

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin (4,2’,4’-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis ), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their 6th lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor κB (NF-κB) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon γ (IFN-γ) were evaluated through ELISA. The effects of ISL on the phosphorylation of IκBα, IKKα/β and p65 in NF-κB signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. NF-κB signaling was inhibited, in which the phosphorylation of p65, IκBα and IKKα/β were suppressed whereas the level of IκBα were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, NF-κB, IL-4 and IL-10 in treating ST.

Isoliquiritigenin attenuates spinal tuberculosis through inhibiting immune response in a New Zealand white rabbit model

Wang, Wenjing,Yang, Baozhi,Cui, Yong,Zhan, Ying The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.4

Spinal tuberculosis (ST) is the tuberculosis caused by Mycobacterium tuberculosis (Mtb) infections in spinal curds. Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is an anti-inflammatory flavonoid derived from licorice (Glycyrrhiza uralensis), a Chinese traditional medicine. In this study, we evaluated the potential of ISL in treating ST in New Zealand white rabbit models. In the model, rabbits (n=40) were infected with Mtb strain H37Rv or not in their $6^{th}$ lumbar vertebral bodies. Since the day of infection, rabbits were treated with 20 mg/kg and 100 mg/kg of ISL respectively. After 10 weeks of treatments, the adjacent vertebral bone tissues of rabbits were analyzed through Hematoxylin-Eosin staining. The relative expression of Monocyte chemoattractant protein-1 (MCP-1/CCL2), transcription factor ${\kappa}B$ ($NF-{\kappa}B$) p65 in lymphocytes were verified through reverse transcription quantitative real-time PCR (RT-qPCR), western blotting and enzyme-linked immunosorbent assays (ELISA). The serum level of interleukin (IL)-2, IL-4, IL-10 and interferon ${\gamma}$ ($IFN-{\gamma}$) were evaluated through ELISA. The effects of ISL on the phosphorylation of $I{\kappa}B{\alpha}$, $IKK{\alpha}/{\beta}$ and p65 in $NF-{\kappa}B$ signaling pathways were assessed through western blotting. In the results, ISL has been shown to effectively attenuate the granulation inside adjacent vertebral tissues. The relative level of MCP-1, p65 and IL-4 and IL-10 were retrieved. $NF-{\kappa}B$ signaling was inhibited, in which the phosphorylation of p65, $I{\kappa}B{\alpha}$ and $IKK{\alpha}/{\beta}$ were suppressed whereas the level of $I{\kappa}B{\alpha}$ were elevated. In conclusion, ISL might be an effective drug that inhibited the formation of granulomas through downregulating MCP-1, $NF-{\kappa}B$, IL-4 and IL-10 in treating ST.

Cosmogenic nuclides (10Be and 26Al) erosion rate constraints in the Badain Jaran Desert, northwest China: implications for surface erosion mechanisms and landform evolution

Tong Zhao,Wenjing Liu,Zhifang Xu,Taoze Liu,Sheng Xu,Lifeng Cui,Chao Shi 한국지질과학협의회 2019 Geosciences Journal Vol.23 No.1

Both tectonics and climate affect surface erosion and change the landform. Long-term surface erosion rates determined by in situ produced cosmogenic nuclides are useful quantitative constraints for landform evolution in geological time scale. Measurements of cosmogenic 10Be and 26Al in the granitic rocks exposed in the Badain Jaran Desert, give a mean erosion rate of 7.3 ± 2.6 m/Ma, which is an order of magnitude higher than those reported in other extremely arid regions. Tectonic activity is supposed to be the first order control on regional erosion rate by comparing the 10Be erosion rates of arid regions with different precipitation ranges and tectonic activities worldwide. However the higher erosion rates in the Badain Jaran Desert compared with other arid regions within the stable tectonic background were attributed to the wind erosion and periodically warmer and wetter climate since late Pleistocene. Besides, the estimated eroded mass flux of 7.8 × 104 t/y suggests that erosion products of bedrocks in the Badian Jaran Desert only contribute minor desert deposits, which indicates massive exogenous materials input to the desert.

Power control of CiADS core with the intensity of the proton beam

Kai Yin,Wenjing Ma,Wenjuan Cui,Zhiyong He,Xinxin Li,Shiwu Dang,Feng Yang,Yuhui Guo,Limin Duan,Meng Li,Yikai Hou 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.4

This paper reports the control method for the core power of the China initiative Accelerator DrivenSystem (CiADS) facility. In the CiADS facility, an intense external neutron source provided by a protonaccelerator coupled to a spallation target is used to drive a sub-critical reactor. Without any control rodinside the sub-critical reactor, the core power is controlled by adjusting the proton beam intensity. Inorder to continuously change the beam intensity, an adjustable aperture is considered to be used at theLow Energy Beam Transport (LEBT) line of the accelerator. The aperture size is adjusted based on theProportional Integral Derivative (PID) controllers, by comparing either the setting beam intensity or thesetting core power with the measured value. To evaluate the proposed control method, a CiADS coremodel is built based on the point reactor kinetics model with six delayed neutron groups. The simulations based on the CiADS core model have indicated that the core power can be controlled stably byadjusting the aperture size. The response time in the adjustment of the core power depends mainly onthe adjustment time of the beam intensity

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.

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.

Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFβ1/Smad2 in Chronic Asthma

Pan Yun,Zhang Dong,Zhang Jintao,Liu Xiaofei,Xu Jiawei,Zeng Rong,Cui Wenjing,Liu Tian,Wang Junfei,Dong Liang 대한천식알레르기학회 2024 Allergy, Asthma & Immunology Research Vol.16 No.1

Purpose: Airway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown. Methods: We studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor β1 (TGFβ1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells. Results: We observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) (r = −0.485, P < 0.01) and FEV1 (%predicted) (r = −0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFβ1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFβ1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFβ1/Smad2 pathway. Conclusions: Our studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFβ1/Smad2 pathway.