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.

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.
Brain ; physiopathology ; Cytokines ; HSP70 Heat-Shock Proteins ; physiology ; Humans ; Inflammation ; pathology ; Neurodegenerative Diseases ; physiopathology ; Neurons ; pathology ; Neuroprotection ; Up-Regulation

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.
Antioxidants ; therapeutic use ; Apoptosis ; Diterpenes, Abietane ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Salvia miltiorrhiza ; chemistry ; Stroke ; drug therapy

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.

Objective:To study the mechanisms that acupuncture therapy of "Shuanggu Yitong" in treating postmenopausal osteoporosis(PMO).Methods:60female SD rats aged 6 months were resected bilateral ovaries and feeded for 90 days in order to make the model of experimental osteoporosis.Then,they were divided into 5 groups such as control group,regular acupoints treated group,"Shuanggu" group,"Yitong" group,"Shuanggu Yitong" group,with 12 rats each group,and the control group without any treatment;Pishu(BL 20),Weishu(BL 21),Shenshu(BL 23),Qihaishu(BL 24) was selected for the regular acupoints treated group;Guanyuan(RN 4),Zusanli(ST 36) for the "Shuanggu" group;and Shenshu(BL 23),Geshu(BL 17),Dazhu(BL 11) for the "Yitong" group;Guanyuan(RN 4),Zusanli(ST 36),Shenshu(BL 23),Geshu(BL 17),Dazhu(BL 11)for the "Shuanggu Yitong" group.Electroacupuncture therapy was given once a day,15 minutes each time,the needles were retained for 10 minutes.Then these rats rested for 1 day after consecutive therapy for 6 days.The therapy lasted for 12 weeks.RT-PCR was used to examine the expression level of interleukin-6(IL-6)mRNA in bone tissue.Results:Compared with control group,the expression level of IL-6mRNA in all acupuncture therapy groups decreased(P0.05).Conclusion:Acupuncture can reduce the expression level of IL-6mRNA in osteoporosis model rats without ovaries and "Shuanggu Yitong" acupuncture therapy is superior to other regular acupuncture therapy.

Objective To investigate in vitro anti-hydatid efficacy on Echinococcus granulosus protoscolex(EgPSC) by using albendazole sulfoxide(ASOX) and its two enantiomeric antipodes, L-ASOX and D-ASOX.Methods Eg protoscoleces were divided into eight groups and cultured in the DMEM culture media under two concentrations(50 ?g/ml and 100 ?g/ml) of ASOX, L-ASOX and D-ASOX respectively.The appropriate controls included(i) a culture containing an equal amount of DMSO and(ii) a culture medium alone.The mortality of EgPSC in each group was daily counted until 100% EgPSC death in some groups.Results Significant difference of EgPSC mortality was found among the three drugs with various concentrations compared to control group(P0.05), but between ASOX group and L-ASOX group(P

0.05).The ratio of TH~+ cells in the experimental group(7.38?0.84)% was higher than that in the control group(0.53?0.17)%,and there was significant statistical difference between the two group(P

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.

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.

Objective To investigate the changes of B lymphocyte subsets ( naive B cells, memory B cells and plasmablasts) in peripheral blood of patients with rheumatoid arthritis ( RA) and their correla-tions with the clinical manifestation and laboratory indexes.Methods Sixty-six patients with RA were di-vided into two groups including the group with active RA and the group with inactive RA according to the dis-ease activity score in 28 Joints (DAS28).A control group with healthy subjects was set up accordingly.The distributions of B lymphocyte subsets in peripheral blood samples were detected with flow cytometry analysis and their correlations with clinical manifestations and laboratory indicators were analyzed.Results ( 1 ) Compared with healthy subjevts, the mean fluorescence intensities ( MFIs) of CD19 and the percentages of memory B cells in peripheral blood of the patients with RA were significantly decreased, while the percenta-ges of naive B cells were increased (P<0.05).The percentages of plasmablasts in the patients with active RA were significantly increased as compared with those of healthy subjects and the patients with inactive RA (P<0.05).(2) The percentages of plasmablasts in peripheral blood of the patients with RA were positively correlated with the joint tenderness count, joint swelling count and joint swelling index (P<0.05).(3) A positive correlation was found between the MFIs of CD19 and the erythrocyte sedimentation rates ( ESRs ) among the patients with RA.The percentages of plasmablasts were positively correlated with C reaction pro-tein (CRP) and anti-cyclic citrullinated peptide (anti-CCP) antibody (P<0.05).(4) The percentages of plasmablasts were also positively correlated with the DAS28 among the patients with RA ( R2=0.343, P<0.01).Conclusion The distributions of B lymphocyte subsets varied among the patients in different stages of RA, which were related to the patient′s clinical symptoms and laboratory indexes.The study suggested that different subsets of the B lymphocytes might play an important role in the pathological process of RA.