1.An acceptor-splice-site mutation responsible for complete androgen insensitivity syndrome
Chinese Journal of Medical Genetics 2001;18(1):14-16
Objcetive To study the molecular mechanism of androgen insensitivity syndrome (AIS) and the relationship among androgen receptor's molecular structure, function and clinical manifestation.Methods PCR-SSCP analysis was carried out to screen exons from B to H of androgen receptor(AR) gene in a cAIS patient for AR gene mutation; direct DNA sequencing of PCR product was performed to find out the location and the pattern of the mutation.Results A newly found point mutation G3346 to T, which is located at intron 5-exon F acceptor splice site in the AR gene, was identified.Conclusion Highly conserved GU-AG structure at splice site plays a crucial role in maintaining normal function of AR.
2.Recent advances in study of sphingolipids on liver diseases.
Shaoyuan WANG ; Jinlan ZHANG ; Dan ZHANG ; Xiuqi BAO ; Hua SUN
Acta Pharmaceutica Sinica 2015;50(12):1551-8
Sphingolipids, especially ceramide and S1P, are structural components of biological membranes and bioactive molecules which participate in diverse cellular activities such as cell division, differentiation, gene expression and apoptosis. Emerging evidence demonstrates the role of sphingolipids in hepatocellular death, which contributes to the progression of several liver diseases including ischaemia-reperfusion liver injury, steatohepatitis or hepatocarcinogenesis. Furthermore, some data indicate that the accumulation of some sphingolipids contributes to the hepatic dysfunctions. Hence, understanding of sphingolipid may open up a novel therapeutic avenue to liver diseases. This review focuses on the progress in the sphingolipid metabolic pathway with a focus on hepatic diseases and drugs targeting the sphingolipid pathway.
3.Research progress of the relationship between microglia and cerebral ischemia.
Wenjiao TAI ; Xuan YE ; Xiuqi BAO ; Xiaoliang WANG ; Dan ZHANG
Acta Pharmaceutica Sinica 2012;47(3):346-53
Microglia are the principal immune effectors in brain and participate in a series ofneurodegenerative diseases. The microglial shapes are highly plastic. The morphology is closely related with their activation status and biological functions. Cerebral ischemia could induce microglial activation, and microglial activation is subjected to precise regulation. Microglia could play either protective or neurotoxic roles in cerebral ischemia. Therefore, regulating the expression of receptors or protein molecules on microglia, inhibiting the excessive activation of microglia and production of pro-inflammatory factors, promoting the release of neuroprotective substances might be beneficial to the treatment of cerebral ischemia. The study about relationship between microglia and cerebral ischemia will shed a light on the treatment of cerebral ischemia. This paper is a review of microglial activation and regulation during cerebral ischemia as well as related therapeutic methods.
4.Therapeutic effect of a natural squamosamide derivative FLZ on Parkinson's disease model mice induced by LPS plus MPTP.
Linghong YU ; Huailing WEI ; Xiuqi BAO ; Dan ZHANG ; Hua SUN
Acta Pharmaceutica Sinica 2013;48(10):1557-62
The aim of this study is to investigate the protective effect of N-[2-(4-hydroxyphenyl)ethyl]-2-(2, 5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)acrylamide (FLZ), a novel synthetic squamosamide cyclic derivative, against Parkinson's disease (PD) model mice induced by the inflammatory bacterial endotoxin, lipopolysaccharides (LPS) and the neurotoxin 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). C57/BL mice were ip injected LPS (5 mg x kg(-1)) once. One week following the LPS injection, mice received a subcutaneous injection of MPTP (25 mg x kg(-1)) once daily for 2 days. Eight weeks later, FLZ (25, 50 and 75 mg x kg(-1)) was orally administered to mice once daily for 60 days. The motor ability of the mice was evaluated by rod climbing test and footprint test. The dopamine (DA) levels in mouse striatum were determined by high performance liquid chromatography system. The tyrosine hydroxylase (TH)-positive cells were showed by immunohistochemical analysis. FLZ treatment significantly improved motor dysfunction of mice challenged by LPS plus MPTP. The increase of TH-positive cell numbers and elevation of DA levels may be contributed to the beneficial effects of FLZ on motor behavior. This study showed FLZ has significant therapeutic effect on LPS plus MPTP induced chronic PD model, which indicates its potential as a new candidate drug to treat PD.
5.Research progress in the study of protective effect of tanshinone IIA on cerebral ischemic stroke.
Dechuan LI ; Xiuqi BAO ; Hua SUN ; Dan ZHANG
Acta Pharmaceutica Sinica 2015;50(6):635-9
Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA.
6.The role of heat shock protein 70 in regulating neuroinflammation.
Wenwen YU ; Xiuqi BAO ; Hua SUN ; Dan ZHANG
Acta Pharmaceutica Sinica 2015;50(8):945-50
Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.
7.The anti-neuroinflammatory effects of dehydromiltirone and related mechanisms
Dechuan LI ; Xiuqi BAO ; Dewu ZHANG ; Hua SUN ; Jungui DAI ; Dan ZHANG
Chinese Pharmacological Bulletin 2016;(2):177-183
Aim To investigate the anti-neuroinflam-matory activities of dehydromiltirone and the underlying mechanisms in LPS-stimulated microglial cell line BV2 cells. Methods BV2 cells were pre-treated with de-hydromiltirone, then stimulated by LPS. The levels of nitric oxide( NO) were measured by Griess assay, and the concentrations of pro-inflammatory cytokines were measured by ELISA assay. Confocal fluorescence mi-croscopy was used to measure the expression of MAC-1, the biomarker of activated BV2 cells. The levels of-inducible nitric oxide synthase ( iNOS ) , cyclooxygen-ase-2 ( COX-2 ) , NF-κB and PI3 K/Akt were deter-mined by Western blot analysis. Results The treat-ment of dehydromiltirone significantly inhibited the pro-duction of NO, TNF-α and IL-6, attenuated the ex-pression of iNOS and COX-2 protein, and dampened the microglial activation in LPS-stimulated BV2 cells. The mechanistic study revealed that dehydromiltirone inhibited the phosphorylation of PI3 K and Akt in LPS-stimulated BV2 cells, and decreased NF-κB activation by suppressing the degradation of IκB. Conclusion dehydromiltirone shows significant anti-neuroinflamma-tory effects through inhibiting PI3 K/Akt phosphoryla-tion and then inhibiting NF-κB signaling pathway.
8.Transplantation of olfactory ensheathing cells for the treatment of obsolete spinal injury in 48 cases
Zuncheng ZHENG ; Chao LIU ; Zhenxing ZHANG ; Daokui WANG ; Xiuqi ZHENG ; Yongjiu JI ; Jiansen ZHENG
Chinese Journal of Tissue Engineering Research 2006;10(9):170-172
BACKGROUND: Changing the local environment of spinal injury promotes the repair and regeneration of injured nerve and recovery of partial nervous function of spinal cord. Transplantation of olfactory ensheathing cells can improve the local internal environment of injured spinal cord.OBJECTIVE: To probe into the effect and safety of transplantation of olfactory ensheathing cells on functional repair of spinal cord and nerve in patients with obsolete spinal injury DESIGN: Self-control experiment.SETTING: Wards of the Department of Surgery, Taian Rongjun Hospital of Shandong Province.PARTICIPANTS: Totally 48 patients admitted for obsolete spinal injury in the Department of Surgery, Taian Rongjun Hospital, between June 2004 and July 2005 were recruited. There were 39 males and 9 females, aged 7 to 59 years with the mean of 36 years.METHODS: ①Cell culture: Olfactory bulb of aborted fetus was digested into single olfactory ensheathing cells, which were then cultured and puri fied for 1 to 2 weeks, and finally made into single cell suspension. ②Operation and cell transplantation: Under general anesthesia, the purified single cell suspension (about 0.05-0.20 mL) of olfactory ensheathing cells was injected into the corresponding spinal injury site through multiple points with home-made syringe of 0.45 mm in diameter. Stitches were taken out at postoperative 10 to 14 days. ③Evaluation of spinal function: Injury Scoring Standard made by American Spinal Injury Association (ASIA) was used for scoring, comparison and statistical analysis at postoperative 1 day and 2 weeks to 2 months. ④Spinal function of 48 patients was observed or followed up through telephone at postoperative 3 weeks to 1 year.MAIN OUTCOME MEASURES: Changes of postoperative sensory function of the patients. Changes of postoperative motor function of the patients. Changes of postoperative automatic nervous system of the patients.RESULTS: ①All the 48 patients had improvement in spinal function, and continued improved tendency was found in the observation and follow-up through telephone at postoperative 3 weeks to 1 year. ②Scoring by ASIA for sensory function was higher after operation than before operation (touch sensation: 56.9, 51.2, P < 0.01; pain sensation: 55.2, 48.3, P < 0.01). Sensory function was improved obviously at the lower shift of sensory level,generally more than 2 segments. ③Scoring by ASIA for motor function was higher after operation than before operation (44.8, 40.7, P < 0.01), but the improvement was slow. ④Scoring by ASIA for automatic nervous system was higher after operation than before operation (18.0, 14.5, P < 0.01); diaphoresis, increased enterokinesia and other automatic nervous system improved earliest.CONCLUSION: Transplantation of olfactory ensheathing cells promotes the spinal and neurofunctional recovery of patients with malignant spinal injury, and the therapeutic method is safe.
9.Effect of probiotics on intestinal flora and related cytokines in infants with cholestatic liver disease
Ling JIANG ; Qingwen SHAN ; Linlin WANG ; Qing TANG ; Xiuqi CHEN ; Shaoli YANG ; Zhi ZHANG
Chinese Journal of Applied Clinical Pediatrics 2015;30(12):945-948
Objective To explore the effects of application of probiotics on intestinal flora and related cytokines in infants with cholestatic liver disease.Methods (1) Eighty-four infants with cholestatic liver disease had been hospitalized from October 2010 to June 2011 in the First Hospital of Guangxi Medical University.The infants with cholestatic liver disease were randomly divided into the probiotic intervention group and the non-probiotic intervention group.Quantification of intestinal bacteria was detected by SYBR Green Ⅰ real-time fluorescent quantitative polymerase chain reaction,then the number of 3 kinds of bacteria before and after the treatment was compared.(2) The indices of liver function,blood ammonia,cholesterol were detected.The levels of serum transforming growth factor-β1,tumor necrosis factor-α(TNF-α)and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay.Results (1) The number of bifidobacterium,lactobacillus and bifidobacterium/escherichia coli (B/E) were significantly increased (all P < 0.01),whereas the number of escherichia coli was significantly decreased in the probiotic intervention group(P < 0.05),however,there were no differences in the non-probiotic intervention group(all P > 0.05).(2)The indices of total billirubin,direct billirubin,γ-Glutamyltransferase,total bile acid,alanine aminotransferase,blood ammonia,alkaline phosphatase were significantly improved after therapy in 2 groups (all P < 0.05).The levels of TNF-α and IL-6 were significantly decreased in the probiotic intervention group (t--7.31,P =0.00;t =-2.90,P =0.01),but there were no differences in the non-probiotic intervention group.The level of BA was significantly decreased in the probiotic intervention group than the non probiotic intervention group (t =-8.37,P =0.00).(3) The B/E value were significantly inverse correlated with level of serum IL-6 (r =-0.796,P =0.01).Conclusions It may help to restore the intestinal flora and balance the immune function in infants with cholestatic liver disease after application of probiotics.
10.Research progress on community health management models for elderly hypertensive patients
Xiaopeng LI ; Xiuqi ZHANG ; Minhua ZHANG ; Weiwen ZHOU
Modern Hospital 2024;24(3):452-456
Objective Summarize domestic and international community health management models and characteristics for elderly hypertensive patients,providing references for the development of community health management in China.Methods Employ literature research to retrieve relevant documents on community health management models for elderly hypertensive pa-tients,and analyze the characteristics and applicability of different models through summarization and comparative analysis.Results In China,community health management models for elderly hypertensive patients include family doctor contracting serv-ices,Hospital-Community-Home health management model,traditional Chinese medicine health management model,"Internet+"health management model,PDCA cycle model,PRECEDE-PROCEED model,and comprehensive community management model.Foreign studies can be categorized into self-management model,Health Rise model,Community Health2(CH2)model,and community pharmacy management model.Conclusion Conducting hypertension health management for elderly patients at the community level is effective,serving as a widely applicable strategy for chronic disease prevention and control.Continued ex-ploration of the scientific and effective aspects of different management models,improving the efficiency and effectiveness of com-munity health management,can contribute more evidence for the formulation of scientific and effective strategies for chronic dis-ease prevention and control.