Chemerin reverses the malignant phenotype and induces differentiation of human hepatoma SMMC7721 cells

Ming Li,Pengcheng Sun,Kaikai Dong,Ye Xin,Aslee TaiLulu,Qinyu Li,Jing Sun,Min Peng,Ping Shi 대한약학회 2021 Archives of Pharmacal Research Vol.44 No.2

Chemerin exhibits an inhibitory eff ect on hepatocellularcarcinoma; however, the underlying mechanismis unclear. Here, low chemerin expression was confi rmedin samples of liver cancer patients and hepatoma cells. Chemerin altered hepatoma cell morphology but had noeff ect on normal hepatocytes. Chemerin inhibited proliferationof several human hepatoma cell lines. Real-time PCRdetection of hepatocellular carcinoma markers showed thatmRNA levels of albumin and A-type gamma-glutamyltransferase increased whereas those of alpha-fetoprotein,alkaline phosphatase, B-type gamma-glutamyl transferase,insulin-like growth factor II, and human telomerase reversetranscriptase decreased in chemerin-treated SMMC7721cells. Western blotting revealed that chemerin up-regulatedalbumin and vimentin expressions, and downregulated alpha-fetoprotein expression. Phosphorylated STAT3 wassignifi cantly up-regulated, whereas phosphorylated ERKand AKT were signifi cantly downregulated by chemerin. Chemerin decreased phosphorylated ERK and AKT expressionand the cell proliferation induced by PI3K activator 740Y-P but could not signifi cantly alter phosphorylated STAT3expression and the cell growth induced by STAT3 inhibitorNSC74859. In conclusion, chemerin reversed the malignantphenotype and induced SMMC7721 cell diff erentiation byinhibiting MAPK/ERK and PI3K/AKT signaling; growthinhibition by chemerin is not directly related to the JAK/STAT signaling pathway. Our study provides novel evidencethat chemerin could be utilized for liver cancer treatment.

Effects of Wind Generation Uncertainty and Volatility on Power System Small Signal Stability

Li-Bao Shi,Li Kang,Liang-Zhong Yao,Shi-Yao Qin,Rui-Ming Wang,Jin-Ping Zhang 대한전기학회 2014 Journal of Electrical Engineering & Technology Vol.9 No.1

This paper discusses the impacts of large scale grid-connected wind farm equipped with permanent magnet synchronous generator (PMSG) on power system small signal stability (SSS) incorporating wind generation uncertainty and volatility. Firstly, a practical simplified PMSG model with rotor-flux-oriented control strategy applied is derived. In modeling PMSG generator side converter, the generator-voltage-oriented control strategy is utilized to implement the decoupled control of active and reactive power output. In modeling PMSG grid side converter, the grid-voltageoriented control strategy is applied to realize the control of DC link voltage and the reactive power regulation. Based on the Weibull distribution of wind speed, the Monte Carlo simulation technique based is carried out on the IEEE 16-generator-68-bus test system as benchmark to study the impacts of wind generation uncertainty and volatility on small signal stability. Finally, some preliminary conclusions and comments are given.

Clinicopathologic Characteristics and Prognoses for Multicentric Occurrence and Intrahepatic Metastasis in Synchronous Multinodular Hepatocellular Carcinoma Patients

Li, Shi-Lai,Su, Ming,Peng, Tao,Xiao, Kai-Yin,Shang, Li-Ming,Xu, Bang-Hao,Su, Zhi-Xiong,Ye, Xin-Ping,Peng, Ning,Qin, Quan-Lin,Chen, De-Feng,Chen, Jie,Li, Le-Qun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment. Aims: To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC). Methods: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups. Results: In the study group, 20 cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM. Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects ($25.7{\pm}4.8$ months vs. $8.9{\pm}3.1$ months, p=0.017). Similarly, the overall survival time of the MO subjects was longer ($31.6{\pm}5.3$ months vs. $15.4{\pm}3.4$ months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time. Conclusions: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.

B-cell Lymphoma 2 rs17757541 C>G Polymorphism was Associated with an Increased Risk of Gastric Cardiac Adenocarcinoma in a Chinese Population

Li, Qiong,Yin, Jun,Wang, Xu,Wang, Li-Ming,Shi, Yi-Jun,Zheng, Liang,Tang, Wei-Feng,Ding, Guo-Wen,Liu, Chao,Liu, Rui-Ping,Gu, Hai-Yong,Sun, Jia-Ming,Chen, Suo-Cheng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducted a hospital based case.control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings.

Numerical analysis and fluid-solid coupling model test of filling-type fracture water inrush and mud gush

Li, Li-Ping,Chen, Di-Yang,Li, Shu-Cai,Shi, Shao-Shuai,Zhang, Ming-Guang,Liu, Hong-Liang Techno-Press 2017 Geomechanics & engineering Vol.13 No.6

The geological conditions surrounding the Jijiapo Tunnel of the Three Gorges Fanba Highway project in Hubei Province are very complex. In this paper, a 3-D physical model was carried out to study the evolution process of filling-type fracture water inrush and mud gush based on the conditions of the section located between 16.040 km and 16.042 km of the Jijiapo Tunnel. The 3-D physical model was conducted to clarify the effect of the self-weight of the groundwater level and tunnel excavation during water inrush and mud gush. The results of the displacement, stress and seepage pressure of fracture and surrounding rock in the physical model were analyzed. In the physical model the results of the model test show that the rock displacement suddenly jumped after sustainable growth, rock stress and rock seepage suddenly decreased after continuous growth before water inrushing. Once water inrush occured, internal displacement of filler increased successively from bottom up, stress and seepage pressure of filler droped successively from bottom up, which presented as water inrush and mud gush of filling-type fracture was a evolving process from bottom up. The numerical study was compared with the model test to demonstrate the effectiveness and accuracy of the results of the model test.

Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression

Shi-Chang Cai,Xiu-Ping Li,Xing Li,Gen-Yun Tang,Li-Ming Yi,Xiang-Shang Hu 한국뇌신경과학회 2021 Experimental Neurobiology Vol.30 No.6

Ischaemic stroke is a common condition leading to human disability and death. Previous studies have shown that oleanolic acid (OA) ameliorates oxidative injury and cerebral ischaemic damage, and miR-186-5p is verified to be elevated in serum from ischaemic stroke patients. Herein, we investigated whether OA regulates miR-186-5p expression to control neuroglobin (Ngb) levels, thereby inhibiting neuronal pyroptosis in ischaemic stroke. Three concentrations of OA (0.5, 2, or 8 μM) were added to primary hippocampal neurons subjected to oxygen–glucose deprivation/reperfusion (OGD/R), a cell model of ischaemic stroke. We found that OA treatment markedly inhibited pyroptosis. qRT–PCR and western blot revealed that OA suppressed the expression of pyroptosis-associated genes. Furthermore, OA inhibited LDH and proinflammatory cytokine release. In addition, miR-186-5p was downregulated while Ngb was upregulated in OA-treated OGD/R neurons. MiR-186-5p knockdown repressed OGD/R-induced pyroptosis and suppressed LDH and inflammatory cytokine release. In addition, a dual luciferase reporter assay confirmed that miR-186-5p directly targeted Ngb. OA reduced miR-186-5p to regulate Ngb levels, thereby inhibiting pyroptosis in both OGD/R-treated neurons and MCAO mice. In conclusion, OA alleviates pyroptosis in vivo and in vitro by downregulating miR-186-5p and upregulating Ngb expression, which provides a novel theoretical basis illustrating that OA can be considered a drug for ischaemic stroke.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Li Shi-Dan,Xing Wei,Wang Shao-Chuan,Li You-Bin,Jiang Hao,Zheng Han-Xuan,Li Xiao-Ming,Yang Jing,Guo De-Bin,Xie Xiao-Yu,Jiang Ren-Qing,Fan Chao,Li Lei,Xu Xiang,Fei Jun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Effects of Wind Generation Uncertainty and Volatility on Power System Small Signal Stability

Shi, Li-Bao,Kang, Li,Yao, Liang-Zhong,Qin, Shi-Yao,Wang, Rui-Ming,Zhang, Jin-Ping The Korean Institute of Electrical Engineers 2014 Journal of Electrical Engineering & Technology Vol.9 No.1

This paper discusses the impacts of large scale grid-connected wind farm equipped with permanent magnet synchronous generator (PMSG) on power system small signal stability (SSS) incorporating wind generation uncertainty and volatility. Firstly, a practical simplified PMSG model with rotor-flux-oriented control strategy applied is derived. In modeling PMSG generator side converter, the generator-voltage-oriented control strategy is utilized to implement the decoupled control of active and reactive power output. In modeling PMSG grid side converter, the grid-voltage-oriented control strategy is applied to realize the control of DC link voltage and the reactive power regulation. Based on the Weibull distribution of wind speed, the Monte Carlo simulation technique based is carried out on the IEEE 16-generator-68-bus test system as benchmark to study the impacts of wind generation uncertainty and volatility on small signal stability. Finally, some preliminary conclusions and comments are given.

Sliding Mode Control for Continuous Casting Mold Oscillatory System Driven by Servo Motor

Sheng-Li Shi,Ke-song Kang,Jian-Xiong Li,Yi-ming Fang 제어·로봇·시스템학회 2017 International Journal of Control, Automation, and Vol.15 No.4

This paper develops an extended-state-observer-based sliding mode control strategy for continuous castingmold oscillatory system driven by servo motor in the presence of matched and mismatched disturbance. Extendedstate observers are employed to estimate the compound disturbances, and the requirement of the derivativeof the compound disturbances to zero is avoided. In order to counteract the mismatched disturbance and attenuatethe chattering phenomenon, a novel sliding surface based on extended state observer is designed for the system. Simulation results illustrate that the proposed controller can achieve better tracking performance and robustness tothe compound disturbance.

BMB Reports : Nutlin-3 downregulates p53 phosphorylation on serine and induces apoptosis in hepatocellular carcinoma cells

( Xin Li Shi ),( Jing Li Liu ),( Lai Feng Ren ),( Nan Mao ),( Fang Tan ),( Nana Ding ),( Jing Yang ),( Ming Yuan Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.4

Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical application for the human hepatocellular carcinoma (HCC) treatment. The reactivation of p53 is an attractive therapeutic strategy in cancer with disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in various cancers. The post-translational modifications of p53 are a hot topic, but there are some controversy ideas about the function of phospho-Ser392-p53 protein in cancer cell lines in response to Nutlin-3. Therefore, we investigated the relationship between Nutlin-3 and phospho-Ser392-p53 protein expression levels in SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that Nutlin-3 induced apoptosis through down-regulation phospho-Ser392-p53 in two HCC cells. The result suggests that inhibition of p53 phosphorylation on Ser392 presents an alternative for HCC chemotherapy. [BMB Reports 2014; 47(4): 221-226]