ATP6V0d2 Suppresses Alveoli Macrophage Alternative Polarization and Allergic Asthma via Degradation of PU.1

Liu Na,Feng Yuchen,Liu Huicheng,Wu Wenliang,Liang Yuxia,Li Pingfei,Wei Zhengping,Wu Min,Tang Zhao-Hui,Han Junyan,Cheng Xiang,Liu Zheng,Laurence Arian,Li Huabin,Zhen Guohua,Yang Xiang-Ping 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.3

Purpose Macrophages are important regulators of environmental allergen-induced airway inflammation and asthma. ATP6V0d2 is a subunit of vacuolar ATPase highly expressed in macrophages. However, the functions of ATP6V0d2 in the regulation of pathogenesis of allergic asthma remain unclear. The aim of this study is to determine the function and related molecular mechanisms of macrophage protein ATP6V0d2 in allergic asthma. Methods We compared the disease severity between female C57BL/6 wild-type and ATP6V0d2−/− mice in an ovalbumin (OVA)-induced asthma model. We also investigated the association of expression of ATP6V0d2, PU.1 and CCL17 with disease severity among asthmatic patients. Results The expression of ATP6V0d2 in sputum cells of asthmatic patients and in the lungs of OVA-challenged mice was enhanced compared to healthy subjects and their counterparts, respectively. However, ATP6V0d2-deficient mice exaggerated inflammatory cell infiltration as well as enhanced alternative activated macrophage (AAM) polarization and mucus production in an OVA-induced asthma model. Furthermore, we found that Atp6v0d2 promoted lysosomal degradation of Pu.1, which induced AAM polarization and Ccl17 production. Among asthma patients, ATP6V0d2 expression was inversely associated with disease severity, whereas PU.1 and CCL17 expression was positively associated with disease severity. Conclusions Our results identify macrophage Atp6v0d2, as an induced feedback inhibitor of asthma disease severity by promoting Pu.1 lysosomal degradation, which may in turn leads to reduced AAM polarization and Ccl17 production.

Adaptive Consensualization for Lipschitz Nonlinear-type Multi-agent Networks with Fixed Topologies

Tang Zheng,Jianxiang Xi,Mei Yuan,Guangbin Liu 제어·로봇·시스템학회 2018 International Journal of Control, Automation, and Vol.16 No.4

Adaptive consensualization problems for Lipschitz nonlinear-type multi-agent networks with fixed topologies are addressed. By using the state errors of the neighboring agents, an adaptive consensus protocol is proposed to deal with the consensualization problems. To eliminate the impacts of the Lipschitz nonlinear dynamics, the structure property of a transformation matrix and the Laplacian matrix, and the Lipschitz condition are well utilized. In the Lyapunov function, a scaling constant is introduced to eliminate the impacts of eigenvalues of the Laplacian matrix, which are the global information of the whole multi-agent networks. Then, an completely distributed consensualization criterion is presented in terms of the linear matrix inequality. Furthermore, an explicit expression of the consensus function and its initial state of this multi-agent network are presented. In the Final, a numerical example is shown to verify the validity of theoretical results.

Protective Effects of Polysaccharide Extracted from Portulacae oleracea L. on Colitis Induced by Dextran Sulfate Sodium

Zheng Wang,Yanni Liang,Dongbo Zhang,Xue Wu,Jingao Yu,Zhen Zhang,Yi Li,Chen Sun,Zhishu Tang,Li Liu 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.2

Polysaccharide from Ma-chi-xian (Portulacae oleracea L., POLP) was prepared and the therapeutic effect on dextran sodium sulfate-induced colitis mice was investigated in this study. The results of clinical activity score and H&E staining confirmed the therapeutic effect of POLP. POLP could diminished the symptoms of colitis and improve colon histopathological structure of the colitis mice. The expression levels of four cytokines were determined. The concentrations of PGE2 and IL-6 were downregulated by POLP treatment. The COX-2 protein expression levels and the STAT3 phosphorylation levels were detected. The results showed that these two protein levels were all increased in colitis and decreased after POLP treatment, indicating that these two proteins were closely related with the protective effect of POLP. Because the synthesis of PGE2 is catalyzed by COX-2 and phosphorylation of STAT3 can induce the expression of COX-2, it was concluded that STAT3 was a key protein related to the POLP exerting its activity in colitis.

Lentivirus-mediated Silencing of Rhomboid Domain Containing 1 Suppresses Tumor Growth and Induces Apoptosis in Hepatoma HepG2 Cells

Liu, Xue-Ni,Tang, Zheng-Hao,Zhang, Yi,Pan, Qing-Chun,Chen, Xiao-Hua,Yu, Yong-Sheng,Zang, Guo-Qing Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Rhomboids were identified as the first intramembrane serine proteases about 10 years ago. Since then, the study of the rhomboid protease family has blossomed. Rhomboid domain containing 1 (RHBDD1), highly-expressed in human testis, contains a rhomboid domain with unknown function. In the present study, we tested the hypothesis that RHBDD1 was associated with proliferation and apoptosis in hepatocellular carcinoma using recombinant lentivirus-mediated silencing of RHBDD1 in HepG2 cells. Our results showed that down-regulation of RHBDD1 mRNA levels markedly suppressed proliferation and colony formation capacity of HepG2 human hepatoma cancer cells in vitro, and induced cell cycle arrest. We also found that RHBDD1 silencing could obviously trigger HepG2 cell apoptosis. In summary, it was demonstrated that RHBDD1 might be a positive regulator for proliferative and apoptotic characteristics of hepatocellular carcinoma.

Protective role of endothelial calpain knockout in lipopolysaccharide-induced acute kidney injury via attenuation of the p38-iNOS pathway and NO/ROS production

Zhifeng Liu,Jingjing Ji,Dong Zheng,Lei Su,Tianqing Peng,Jing Tang 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

To explore the role of calpain and its signaling pathway in lipopolysaccharide (LPS)-induced acute kidney injury (AKI), animal models of endotoxemia were established by administration of LPS to mice with endothelial-specific Capn4 knockout (TEK/Capn4−/−), mice with calpastatin (an endogenous calpain inhibitor) overexpression (TgCAST) and mice with myeloid-specific Capn4 knockout (LYZ/Capn4−/−). Mouse pulmonary microvascular endothelial cells (PMECs) were used as a model of the microvascular endothelium and were stimulated with LPS. Renal function, renal inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) expression, cellular apoptosis, plasma and renal levels of NO and reactive oxygen species (ROS), and phosphorylation of mitogenactivated protein kinase (MAPK) family members (p38, ERK1/2, and JNK1/2) were examined. Moreover, a calpain inhibitor, calpastatin overexpression adenoviruses and MAPK inhibitors were used. Significant renal dysfunction was induced by LPS stimulation, and recovery was observed in TEK/Capn4−/− and Tg-CAST mice but not in LYZ/ Capn4−/− mice. Endothelial Capn4 knockout also abrogated the LPS-induced increases in renal iNOS expression, caspase-3 activity and apoptosis and plasma and renal NO and ROS levels but did not obviously affect renal eNOS expression. Moreover, LPS increased both calpain and caspase-3 activity, and only the expression of iNOS in PMECs was accompanied by increased phosphorylation of p38 and JNK. Inhibiting calpain activity or p38 phosphorylation alleviated the increased iNOS expression, NO/ROS production, and cellular apoptosis induced by LPS. These results suggest that endothelial calpain plays a protective role in LPS-induced AKI by inhibiting p38 phosphorylation, thus attenuating iNOS expression and further decreasing NO and ROS overproduction-induced endothelial apoptosis.

Inhibition of Dll4/Notch1 pathway promotes angiogenesis of Masquelet’s induced membrane in rats

Qian Tang,Haimin Jin,Minji Tong,Gang Zheng,Zhongjie Xie,Shangkun Tang,Jialei Jin,Ping Shang,Huazi Xu,Liyan Shen,Yu Zhang,Haixiao Liu 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

The Masquelet’s induced membrane technique for repairing bone defects has been demonstrated to be a promising treatment strategy. Previous studies have shown that the vessel density of induced membrane is decreased in the late stage of membrane formation, which consequently disrupts the bone healing process. However, relatively little is known about certain mechanisms of vessel degeneration in the induced membrane tissue and whether promotion of angiogenesis in induced membranes can improve bone regeneration. Here, we showed that the Delta-like ligand 4/ Notch homolog 1 (Dll4/Notch1) pathway was relatively activated in the late stage of induced membrane, especially at the subcutaneous site. Then, DAPT, a classical γ-secretase inhibitor, was applied to specifically inhibit Notch1 activation, followed by up-regulation of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31 expression. DAPTmodified induced membranes were further confirmed to contribute to bone regeneration after autogenous bone grafting. Finally, in vitro experiments revealed that knocking down Notch1 contributed to the functional improvement of endothelial progenitor cells (EPCs) and that DAPT-treated induced membrane tissue was more favorable for angiogenesis of EPCs compared with the vehicle group. In conclusion, the present findings demonstrate that Dll4/ Notch1 signaling is negatively associated with the vessel density of induced membrane. Pharmacological inhibition of Notch1 attenuated the vessel degeneration of induced membrane both in vitro and in vivo, which consequently improved bone formation at the bone defect site and graft resorption at the subcutaneous site.

Differences in Clinical Characteristics and Surgical Outcomes of Patients with Ischemic and Hemorrhagic Pituitary Adenomas

Jingpeng Liu,Peng Huang,Xiaoqing Zhang,Yong Chen,Xin Zheng,Rufei Shen,Xuefeng Tang,Hui Yang,Song Li 대한신경외과학회 2023 Journal of Korean neurosurgical society Vol.66 No.1

Objective : Ischemia and hemorrhage of pituitary adenomas (PA) caused important clinical syndrome. However, the differences on clinical characteristics and surgical outcomes between these two kinds apoplexy were less reported. Methods : A retrospective analysis was made of patients with pituitary apoplexy between January 2013 and June 2018. Baseline and clinical characteristics before surgery were reviewed. All patients underwent transsphenoidal surgery and were followed up at least 1 year. Results : Total 67 cases (5.8%) among 1147 pituitary tumor patients were enrolled, which consisted of 28 (~2.4%) ischemic PA and 39 (~3.4%) hemorrhagic PA. There were more male patients in the ischemic group compared with hemorrhagic group (78.6% vs 53.8%, p=0.043). However, the mean age, tumor size and functional tumor ratio were significant higher in the hemorrhagic group. Headache was more common in ischemic PA (82.1%) than that of hemorrhagic PA (51.3%, p=0.011). Magnetic resonance imaging findings found that mucosal thickening and enhancement of the sphenoid sinus was observed in 15 ischemic PA patients (n=27, 55.6%), but none in patients with hemorrhagic PA (n=38, p<0.0001). It was worth noting that the rate of pre-surgical hypopituitarism in ischemic PA patients were seemed higher than that in hemorrhagic PA patients, but not significant. The two groups got a total tumor resection rate at 94.1% and 92.9%, independently. No significant difference on the operative time, blood loss in operation and complications in perioperative period was observed in two groups. After operation, cranial nerve symptoms recovered to normal at 81.8% of ischemic PA patients and 82.6% of hemorrhagic PA patients. Importantly, the incidence of postoperative hypopituitarism partially decreased in both groups, among which the rate of hypothyroidism in ischemic PA patients significantly decreased from 46.4% to 18.5% (p=0.044). Conclusion : Patients with ischemic PA presented different clinical characteristics to the hemorrhagic ones. Transsphenoidal surgery should be considered for the patients with neuro-ophthalmic deficits and might benefit for pituitary function recovery of the apoplectic adenoma patients, especially pituitary thyroid axis in ischemic PA patients.

FSCB phosphorylation in mouse spermatozoa capacitation

( Shun Li Liu ),( Bing Ni ),( Xiang Wei Wang ),( Wen Qian Huo ),( Jun Zhang ),( Zhi Qiang Tian ),( Ze Min Huang ),( Yi Tian ),( Jun Tang ),( Yan Hua Zheng ),( Feng Shuo Jin ),( Yan Feng Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.8

It is generally accepted that spermatozoa capacitation is associated with protein kinase A-mediated tyrosine phosphorylation. In our previous study, we identified the fibrous sheath CABYR binding protein (FSCB), which was phosphorylated by PKA. However, the phosphorylation status of FSCB protein during spermatozoa capacitation should be further investigated. To this aim, in this study, we found that phosphorylation of this 270-kDa protein occurred as early as 1 min after mouse spermatozoa capacitation, which increased over time and remained stable after 60 min. Immunoprecipitation assays demonstrated that the tyrosine and Ser/Thr phosphorylation of FSCB occurred during spermatozoa capacitation. The extent of phosphorylation and was closely associated with the PKA activity and spermatozoa motility characteristics. FSCB phosphorylation could be induced by PKA agonist DB-cAMP, but was blocked by PKA antagonist H-89.Therefore, FSCB contributes to spermatozoa capacitation in a tyrosine-phosphorylated format, which may help in further elucidating the molecular mechanism of spermatozoa capacitation. [BMB reports 2011; 44(8): 541-546]

Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients

Wen-Yue Liu,Xiaofang Zhang,Gang Li,Liang-Jie Tang,Pei-Wu Zhu,Rafael S. Rios,Kenneth I. Zheng,Hong-Lei Ma,Xiao-Dong Wang,Qiuwei Pan,Robert J. de Knegt,Luca Valenti,Mohsen Ghanbari,Ming-Hua Zheng 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.2

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. Methods: We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. Results: Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. Conclusions: The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

Differential die-away technology applied to detect special nuclear materials

Lianjun Zhang,Mengjiao Tang,Chen Zhang,Yulai Zheng,Yong Li,Chao Liu,Qiang Wang,Guobao Wang Korean Nuclear Society 2023 Nuclear Engineering and Technology Vol.55 No.7

Differential die-away analysis (DDAA) technology is a special nuclear material (SNM) active detection analysis technology. Be a nuclear material shielded or not, the technology can reveal the existence of nuclear materials by inducing fission from an external pulsed neutron source. In this paper, a detection model based on DDAA analysis technology was established by geant4 Monte Carlo simulation software, and the optimal sensitivity of the detection system is achieved by optimizing different configurations. After the geant4 simulation and optimization, a prototype was established, and experimental research was carried out. The result shows that the prototype can detect 200 g of ²³⁵U in a steel cylinder shield that's of 1.5 cm in inner diameter, 10 cm in thickness and 280 kg in weight.