1.Bone morphogenetic protein receptor Ⅱ signaling pathway and pulmonary arterial hypertension:updates and expectations
Jin WANG ; Lili XIANG ; Xiaohui LI
Chinese Journal of Pharmacology and Toxicology 2017;31(2):119-130
The identification of the relationships between mutations of the bone morphogenetic protein type Ⅱ receptor (BMPR2) and pulmonary arterial hypertension (PAH) has been considered to be one of the most significant discoveries in this area in the 21st century. And BMPR2 mutation is responsible for the majority of hereditary PAH as well as some of idiopathic PAH. Furthermore, clinical and animal expreimental research over the past few years has revealed that BMPR2 signaling pathway plays a critical role in the initiation and progress of PAH, by participateing in the pathogenesis of PAH. In addition, the potential that BMPR2 signaling pathway is used as a therapeutic target is being evaluated. This review summarizes our current understanding of the role of BMPR2 mutations in PAH from the perspectives of genetics, epigenetics, inflammation as well as interactions with other significant pathways.
2.Design of artifact-free head holder for small animal imaging
Xiaohui XIANG ; Xiaoqing WEN ; Shihai XIA
China Medical Equipment 2015;(10):1-4
Objective:To design a kind of head holder for small animal imaging without artifact. Methods: The head holder was designed for small animal imaging according to rodent head stereotaxic apparatus with lightweight and easy molding material (polymethyl methacrylate). The holder can be easily made with ordinary lathe and can be easily operated in small animal imaging device. Results:After the trial in small animal PET-CT, the holder can effectively solve the problems in small animal imaging such as the artifact caused by tiny displacement, tilt head position, deviating from the central field of view and respiratory depression. Conclusion: The small animal imaging device was designed in simple structure to overcome the shortcomings of the existing technology. The operation of the device is simple, which is worthy of popularization head holder of application.
3.STAT3 signaling in pathogenesis of pancreatitis
Linfei ZONG ; Xiaohui XIANG ; Shihai XIA
Chinese Journal of Pathophysiology 2016;32(3):558-563
Signal transducer and activator of transcription 3 (STAT3), an acute-phase response protein, is ac-tivated to over-express by cytokines .STAT3 also acts as a transcriptional factor to regulate the expression of cytokines .O-ver-expression of cytokines is accompanied by STAT 3 activation and over-expression in acute pancreatitis .Meanwhile , the proliferation of pancreatic stellate cells in chronic pancreatitis is mediated by STAT 3.In this review, the research progress in STAT3 function is summarized to elaborate its potential role in the pathogenesis of pancreatitis .
4.Research progress of TLR4 signaling pathway related miRNAs in inflammatory response
Ruyue LI ; Xiaohui XIANG ; Bin ZHANG ; Shihai XIA
Tianjin Medical Journal 2017;45(7):771-776
Toll-like receptor 4 (TLR4) plays an important role in inflammation and immune response.MicroRNAs (miRNAs) are involved in the regulation of TLR4 signaling pathway in multiple levels and various molecules,which play an important role in inflammatory reaction.A variety of miRNAs are involved in the regulation of TLR4 signaling pathway,and the TLR4 signaling pathway can induce a variety of miRNAs.Chronic diseases such as diabetes,Alzheimer's disease and cardiovascular disease are closely related to inflammatory response.The regulatory role of TLR4 signaling related miRNAs has attracted much attention in inflammatory diseases.In this review,the research progress of TLR4 signaling pathway related miRNAs in the regulation of inflammatory response is summarized,which provides a new research direction for the clinical diagnosis and treatment of inflammatory response related diseases.
5.The interventional therapy of the metal foreign matter in the stomach
Xiang HE ; Heping ZHANG ; Haiying JIN ; Xiaohui WANG ; Sihai ZHAO
Chinese Journal of Radiology 2001;0(09):-
Objective To investigate the interventional therapy and its value in the metal foreign matter in the stomach. Methods Eight patients with metal foreign matter in the stomach was studied. All patients were male, and their age ranged from 28 to 46 years with the mean age of 32.2 years. All patients had the medical history of swallowing metal foreign matter in compulsory detoxification or imprisonment. The catheter was inserted into the stomach lead by guide wire lubricated by paraffine. Then the guide wire was withdrawn and a 2.6 m long guide wire was folded in the middle and was inserted into the sromach through the catheter. A loop was made on the guide wire, and the loop was controlled to to hitch the forigen mater, then the guide wire was drawn out slowly . Results A total of 12 metal foreign matters in the stomach in all 8 patients were taken out safely, and no comqlications occurred. Conclusion The interventional therapy for the metal foreign matter in the stomach is simply, minimal invasive, cheap, effective, and with little complication. This therapy is a clinic treatment, the patient is glad to accept, and is the ideal therapy for foreign matter in the stomach.
6.Blockade of CLC-3 chloride channel inhibited the viability and invasion of colorectal cancer cells
Yanping WANG ; Linsong JI ; Hongwei FAN ; Xiaohui XIANG ; Wei XU
Chinese Journal of Clinical Oncology 2016;43(9):361-365
Objective:To examine the expression of CLC-3 in colorectal tissues and the effect of CLC-3 on the viability and invasion of colorectal cancer (CRC) SW480 and SW620 cells. Methods:The mRNA levels of CLC-3 in CRC cell lines were determined by RT-PCR. CLC-3 expression was inhibited by adding DIDS or NPPB to the CRC cells. Subsequently, cell viability and invasion were assessed by CCK-8 assay and Transwell assay, respectively. In addition, the effects of DIDS and NPPB on the Wnt orβ-catenin signaling pathways were de-termined by Western blot analysis. Results:The mRNA level of CLC-3 was remarkably increased in the CRC tissues compared with that in normal colorectal tissues (P<0.05) and was positively correlated with the T stage of CRC. The blockade of CLC-3 inhibited the viability and invasion of CRC cells (P<0.05). The expression ofβ-catenin, C-myc, cyclin D1, Ki-67, and survivin were evidently reduced by the in-hibition of CLC-3 (P<0.05). Conclusion:The inhibition of CLC-3 decreases the cell viability and invasion of CRC cells by reducing the ex-pression of the proteins related to the Wnt orβ-catenin signaling pathway.
7.Oxymatrine suppressed the activation of pancreatic stellate cells and p38-MAPK mRNA expression in vitro
Wei XU ; Kai CHEN ; Xiaohui XIANG ; Shihai XIA
Chinese Journal of Pancreatology 2016;16(3):185-188
Objective To clarify whether oxymatrine ( OM) could suppress the activation of pancreatic stellate cells ( PSC) and explore the potential molecular mechanism .Methods The proliferation of PSC line LTC 14 being activated by TGF-β1 with OM treatment at different concentrations (OM group) was measured. SOD level was determined by ELISA and p 38-MAPK mRNA was determined by real-time PCR.Results The proliferation of PSC in the control group , 0.1, 0.5, 1, 2, 5 g/L OM group was (1.51 ±0.08), (1.50 ± 0.07), (1.15 ±0.04), (1.15 ±0.04), (1.08 ±0.06), and (1.08 ±0.10), respectively.The level of the control group was lower than the groups where the concentration of OM reached or exceeded 0.5mg/ml ( all P=0.000).SOD level of LTC 14 cells in the control group, TGF-β1 group, 0.5 and 1 g/L OM group was (0.087 ±0.005), (0.073 ± 0.004), (0.085 ± 0.010), and (0.086 ± 0.007), respectively. No statistically significant difference existed among the groups (P=0.095).The p38-MAPK mRNA expression of PSC in the control group, TGF-β1 group, 0.5, and 1 g/L OM group was (1.000 ±0.000), (1.979 ± 0.505), (0.606 ±0.111), and (0.303 ±0.159), respectively.The p38-MAPK mRNA level of TGF-β1 group was higher than that of the control group (P=0.002), and that of 0.5 mg/ml OM group and 1 mg/ml OM group was lower that of TGF-β1 group ( P=0.000 ) , while no statistical difference was found between 0.5 mg/ml OM group and 1 mg/ml OM group.Conclusions OM could suppress the activation of PSC in vitro and the suppression of p38-MAPK mRNA expression may be involved .
8.Effects of all-trans retinoic acid on sensitivity of gastric cancer cells to ra-diotherapy
Yanping WANG ; Xianqun ZHAO ; Xiangdong ZHANG ; Wei XU ; Xiaohui XIANG
Chinese Journal of Pathophysiology 2016;32(8):1440-1444
AIM:To investigate the effect of all-trans retinoic acid ( ATRA) on the viability of gastric cancer cell SGC-7901 and the sensitivity to radiotherapy .METHODS:MTT assay was used to examine the cell viability .Radio-sensitivity and cell cycle were determined by colony formation assay and flow cytometry , respectively .The mRNA levels of Bax, Bcl-2, survivin and NF-κB in the cells were measured by RT-qPCR.RESULTS: ATRA inhibited the viability of SGC-7901 cells in a concentration-dependent manner .The maximal inhibition was at concentration of 8 μmol/L.Colony formation assay revealed that the combination of ATRA with X-ray treatment significantly reduced the values of D 0 and Dq, and shifted down the fitting survival curve , as compared with radiotherapy alone .Moreover , ATAR markedly decreased the percentage of G2/M phase in the SGC-7901 cells (P<0.05).In addition, following ATRA treatment, the mRNA levels of Bcl-2 and survivin were decreased (P<0.05), whereas the mRNA levels of Bax and NF-κB were increased (P<0.05). CONCLUSION:ATRA enhances the sensitivity of SGC-7901 cells to radiotherapy , inhibits G2/M arrest and regulates the mRNA expression of Bax , Bcl-2, survivin and NF-κB.
9.Effects of different doses of ketamine on systemic inflammatory cytokines at early stage of rabbits with severe burn
Jianguo XIA ; Jinyi XIANG ; Xiaohui YUAN ; Zhuo CHEN ; Lin LIU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;(4):386-389
Objective To investigate the effect of different doses of ketamine on inflammatory cytokines in rabbits with severe burn at early stage and preliminarily approach its regulatory action on early stage of inflammatory reaction due to stress of trauma.Methods Forty healthy male New Zealand rabbits were randomly divided into four groups in accord with the random number table method: normal control group, scald model group, ketamine analgesia group and ketamine anesthesia group. Before scald, pentobarbital sodium was used for anesthesia, afterwards catheters were inserted into internal jugular vein and internal carotid artery respectively ready for use, and 24 hours later, Ⅲ degree scald at the animal back and buttocks occupying 30% total body surface area (TBSA) was performed as the scald model for all the rabbits except those in normal control group. In ketamine analgesia group, after scald for 0.5 hour, 0.5 mg/kg ketamine intravenous injection was given to the rabbits as the loading dosage and then persistent intravenous pump infusion of 9μg·kg-1·min-1 ketamine was applied for all together 24 hours. In ketamine anesthesia group, after scald for 0.5 hour, 1.5 mg/kg ketamine intravenous injection was given to the rabbits, and then persistent intravenous pump infusion of 45μg·kg-1·min-1 ketamine was applied for 4 hours to maintain systemic anesthesia. In normal control and scald model groups, only intravenous infusion of equal amount of normal saline was given to the rabbits. The amount of intravenous transfusion in each group and the total dosages of ketamine used in ketamine analgesia group and ketamine anesthesia group were recorded. Before scald and 0.5, 6, 12, 24 hours after scald, arterial blood gas analyses were made, and the levels of serum interleukins (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were determined.Results Although the indexes of blood gas analysis were changed in the four groups, they were all in the normal range, showing that the respiratory function was in the normal range and indirectly reflecting that the circulatory function was also in the normal range, thus the effects on cytokines by factors of respiratory and circulatory functions were ruled out. The levels of IL-1, IL-6 and TNF-α before scald showed no statistically significant differencesamong the four groups (allP > 0.05). From 0.5 hour after scald, the levels of IL-1, IL-6 and TNF-α were markedly higher in model group than those of normal control group [IL-1 (ng/L): 30.27±0.93 vs. 13.79±1.11, IL-6 (ng/L): 47.22±1.49 vs. 46.31±4.12, TNF-α (ng/L): 243.39±20.85 vs. 190.95±14.97, allP < 0.05], and the situation continued until 24 hours after scald; the levels of IL-1, IL-6 and TNF-α from 6 hours after scald were significantly decreased in ketamine analgesia and ketamine anesthesia groups compared with those in the model group, and from 12 hours after scald, the degrees of descent in levels of the above indexes in ketamine analgesia group were more obvious than those in ketamine anesthesia group [IL-1 (ng/L): 19.28±2.51 vs. 40.12±10.31, IL-6 (ng/L): 52.10±4.23 vs. 72.20±10.11, TNF-α (ng/L): 246.03±20.74 vs. 313.71±27.34, allP < 0.05].Conclusion The low-dose ketamine analgesia and ketamine anesthesia have certain degree of inhibitory effect on the expression and release of inflammatory cytokines at the early stage in rabbits with severe burn, the effect of long-term low-dose ketamine analgesia being more significant.
10.Mechanism of biological actions of quercetin based on biomolecular network.
Xiaohui YAN ; Changhai SUN ; Lisha NA ; Xiang LI ; Hengxin REN ; Shuting ZHANG
Acta Pharmaceutica Sinica 2014;49(5):661-5
The mechanism of biological actions of quercetin was studied by using metabolomic method and biomolecular network. HPLC-MS was used to analyze the serum metabolome in rats of blank group and quercetin administration group rats, and MS data were processed by MATLAB software. With multivariate statistical analysis of serum metabolite profiles, a clear separation among blank group and quercetin administration group was achieved, potential biomarkers were selected according to the parameters of variable importance in the projection (VIP) and identified according to MS information and database retrieval. Four compounds, related enzymes, action targets and metabolic pathways had been confirmed, namely retinoic acid and RARbeta, arachidonate and COX-2, 3, 5-diodotyrosine and TPO, uridine diphosphate glucose and PDEs. The mechanism of quercetin enhancing ability of retinoic acid on the induction of RARbeta, activating TPO, using as COX-2 and PDEs inhibitor was approved by biomolecular network and related literatures. In this study, a mechanism of multiple biological actions of quercetin was evaluated at the level of the biomolecular network, metabolomics and biomolecular network can be used to investigate the biological effects mechanism of quercetin, which provided a new method to further revealing mechanism of drug action.