SIGIRR, a member of the interleukin 1 receptor superfamily, is also known as a single immunoglobulin (Ig)-related receptor, which is believed to play a key role in the development of inflammation and the regulation of anti-inflammatory effects. Some studies believe that the abnormal down-regulation of SIGIRR can lead to intestinal inflammation, pyelonephritis, systemic lupus erythematosus and other diseases, but it can promote tumor growth and potentially cause anti-tumor immune damage when its genes are overexpressed. Therefore, the role of SIGIRR in disease occurrence and development is considered a double-edged sword. At present, the detailed molecular mechanism of SIGIRR′s biological role is not fully understood. This article reviews the functions of SIGIRR in the occurrence and development of immune-related diseases and immune regulation, as well as related cell signaling pathways, which have been discovered and confirmed.

Objective To investigate the effect of insulin-like growth factor- Ⅰ ( IGF- Ⅰ ) on the proliferation and osteogenesis of human periodontal ligament stem cells ( hPDLC ) under three-dimensional (3D) culture system. Methods Human periodontal cells were isolated from the ligament of surgically extracted human teeth, and through the limiting dilution assay, got mono-clone of the cell, hPDLCs were isolated from MesenPRO RS medium. Rotary cell culture system (RCCS) was enrolled to set 3D environment. Control group and experiment groups were assigned according to the concentration of IGF- Ⅰ .There were 5 level of experiment groups (0.1,1,10,50,100 μg/L). Proliferation was tested with methyl thiazolyl tetrazolium ( MTT), and alkine phosphatase (ALP) level was assayed by spectrophotometer to analyze the osteogenesis of hPDLCs. Gene expression of ostetocalcin(OCN)and type Ⅰ collagen (Col Ⅰ )were assayed by reverse transcriptase polymerase chain reaction(RT-PCR). Results In 3D culture system,the effect of IGF- Ⅰ on cell proliferation was significantly different between control group and experiment groups( P ＜ 0.05 ), and there showed significant differences between the group of 0.1 μg/L ( 0.219 ±0.021 ) IGF- Ⅰ and the groups of 50, 100 μg/L(0.287 ±0.011,0.293 ±0.012). However, there showed no significant differences among other groups. Significant differences of ALP activity were observed between the control group and experiment groups, and between the groups of 1, 10 μg/L(0.304 ±0.020, 0.310 ±0.013) and that of 50, 100 μg/L (0.347 ±0.011, 0.344 ±0.010) (P ＜0.05). While no significantdifferences were detected between the group of 1 μg/L and that of 10 μg/L, nor between the group of 50 μg/L and that of 100 μg/L. Expressions of Col Ⅰ and OCN in mRNA and protein level both showed dose-dependent increase. Conclusions In 3D culture system, in the scale of 0.1-100 μg/L, the effect of IGF-Ⅰ on the proliferation of hPDLCs increased dose-dependently. 100 μg/L IGF- Ⅰ promotes osteogenesis of the cells significantly.

OBJECTIVETo investigate the effect of insulin-like growth factor- I (IGF- I) on the proliferation and alkaline phosphatase (ALP) activity of human periodontal ligament cells (hPDLCs) under three-dimensional (3D) culture system.

METHODSThe hPDLCs were cultured from periodontium of human teeth by the outgrowth method. Rotary cell culture system (RCCS) was enrolled to set 3D culture system. Samples were set to four groups: Negative control group, positive control group (3D group, IGF-I group), and experimental group (3D with IGF- I group). Proliferation was tested with methylthiazolyl tetrazolium (MTT), and ALP activity was assayed by spectrophotometer at 1, 3, 5, 7 d respectively.

RESULTSCompared with that of negative control group, cell proliferation increased significantly in 3D with IGF-I group since 3 d (P < 0.05). Besides, the cell proliferation of 3D with IGF-I group was significantly higher than that of 3D group (P < 0.05). ALP activity of 3D with IGF- I group was significantly higher than that of negative control group, and 3D group at 3, 5, 7 d (P < 0.05).

CONCLUSIONIGF-I significantly promotes the proliferation and ALP activity of hPDLCs under 3D culture system.

Alkaline Phosphatase ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Humans ; Insulin-Like Growth Factor I ; Periodontal Ligament ; Somatomedins

To investigate the cell-killing effect and its possible mechanism of rClone30-hDR5 in combination with TRAIL on human hepatic carcinoma (HCC) cell line, first of all, recombinant plasmid pee12.4-hDR5 was introduced into HepG2 cells by liposome transfection. After five rounds of screening by flow cytometry, HepG2 cells expressing high levels of DR5 on cell surface were isolated. The cytotoxicity of TRAIL to selected cells was higher than that of TRAIL to HepG2 cells by MTT method (P < 0.01). The result suggested that the cloned hDR5 gene had biological activity. MTT assay showed that, rClone30- hDR5 in combination with TRAIL more efficiently inhibited the tumor growth of HepG2 cells compared to rClone30-hDR5 or TRAIL in vitro. The results of Annexin V-FITC/PI staining and Quantitative Real-time PCR indicated that rClone30-hDR5 in combination with TRAIL significantly increased the mRNA levels of caspase 3 and caspase 8, and induced the apoptosis of tumor cells. HepG2 cells were infected with rClone30-hDR5 or rClone30 at MOI of 1. The expression of hDR5 on tumor surface increased significantly by rClone30-hDR5 compared to that by rClone30, which contributed to the sensitivity to TRAIL. In conclusion, rClone30-hDR5 in combination with TRAIL has potential application value in cancer treatment.
Apoptosis ; Carcinoma, Hepatocellular ; pathology ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Drug Synergism ; Hep G2 Cells ; Humans ; Liver Neoplasms ; pathology ; Real-Time Polymerase Chain Reaction ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; pharmacology ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology ; Transfection

OBJECTIVETo compare the efficacy and safety of PEG-IFNalpha-2b (Peg-Intron) with IFNalpha-2b (Intron A) in treating HBeAg positive chronic hepatitis B patients.

METHODSTwo hundred thirty chronic hepatitis B (CHB) patients eligible to the following criteria were enrolled into this study: HBsAg and HBeAg(Abbott kit) positive for at least 6 months, serum HBV DNA > or =10(5) copies/ml (real time PCR, LLQ <10(3) copies/ml) and ALT > or =2 x ULN. After 1:1 randomization, the patients received PegIntron (group A: 1.0 microg/kg body weight, SC, once a week) or Intron A (group B: 3 MIU SC, three times a week) for 24 weeks, and followed up for 24 weeks.

RESULTS(1) In groups A and B, respectively, 80.87% and 83.48% were males; their median ages were 31.0 and 32.0 years old; their median body weights were 65.6 and 65.5 kg; mean serum HBV DNA loads were 8.06 log10 and 7.99 log10; their mean ALT values were 4.17 x ULN and 3.77 x ULN. All of the above parameters between the two groups had no statistically significance differences. (2) At the end of treatment and after follow-up, compared to the Intron A group, the PegIntron group showed better response (including complete and partial response rate, HBV DNA undetectable rate, HBeAg seroconversion rate), but the differences of all of them had no statistical significance. The rate of HBeAg loss was higher in patients receiving PegIntron after follow-up (P = 0.0424). (Table 2) (3) PegIntron and Intron A reduced serum HBV DAN persistently during the therapy. Mean reduction at the end of the treatment was much higher in the PegIntron group than in the Intron group (2.22 log10 copies/ml vs 1.66 log10 copies/ml, P = 0.0283). (4) The overall incidence of adverse events (AEs) in the PegIntron group was similar to that of the Intron A group (94.78% vs 95.65%). The AEs associated with PegIntron administration were similar in nature to those with Interon A, such as influenza-like symptoms, fever, fatigue, headache, nausea, etc and the differences of their incidences had no statistical significance.

CONCLUSIONSThe efficacy and safety of PEG-IFNalpha-2b treatment for CHB patients seems to be better than that of IFNalpha-2b; however, further studies are needed to confirm it.

Adolescent ; Adult ; Aged ; Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; Recombinant Proteins

Objective To construct an over-expressing plasmid containing full length of PELP1 gene and investigate the characterization of PELP1 expressions in different tissues.Methods Full length PELP1 gene was cloned using RT-PCR product of MCF-7 total RNA as the template.The PELP1 gene fragament was amplified by PCR and two enzyme sites EcoR I and Xho I were added.Then PELP1 gene was cloned into the pIRES2-EGFP palsimd (containing EcoR I and Xho I enzyme sites) to make reconstructed plasmid pIRES2-EGFP-PELP1.Enzyme digestion and sequencing were employed to assess the integrity and correctness of PELP1 gene cloned.The plasmid pIRES2-EGFP-PELP1 was transfected into human periodontal ligament stem cells,and the expression of PELP1 was examined by quantitative real-time-PCR or Western-blotting.Results The integrity and correctness of PELP1 gene were confirmed by digestion and sequencing.Conclusions The full length of PELP1 gene from MCF-7 cell was successfully cloned and over-expression plasmid pIRES2-EGFP-PELP1 constructed.

Objective To observe the effect of electroacupuncture(EA)on the expression of NKCC1,KCC2 and activation of microglia in spinal dorsal horn of paclitaxel(PTX)-induced neuropathic pain rats and its possible mechanism.Methods Male SD rats were randomly divided into the vehicle group(vehicle),the PTX group,the PTX+EA group and the PTX+sham EA group,with 12 rats in each group.The rat model of PTX-induced neuropathic pain was established by intraperitoneal injection of PTX.After modeling,EA was applied to"Zusanli"and"Yanglingquan"for 7 days in the PTX+EA group.Paw withdrawal threshold and paw withdrawal latency were tested at 2 days before and 1,3,5,7,14 and 21 days after PTX injection.Immunofluorescence and Western blot assay were used to detect expression levels of sodium-potassium-chloride cotransporter 1(NKCC1),potassium-chloride cotransporters 2(KCC2)and microglia markers-ionized calcium binding adapter molecule 1(Iba1)in spinal dorsal horn.Results Compared with the vehicle group,mechanical and thermal hyperalgesia of both hind feet were found in the PTX group,and the expression of NKCC1 and the number of activated microglia in dorsal horn tissue of spinal cord were increased.Compared with the PTX group,mechanical and thermal hyperalgesia were significantly improved in the PTX+EA group at day 14 and 21,and the expression levels of NKCC1 and Iba1 in dorsal horn tissue of spinal cord were decreased.There was no significant difference in KCC2 expression between the four groups.Conclusion Electroacupuncture can effectively relieve paclitaxol-induced neuropathic pain,which may be related to the inhibition of NKCC1 expression and microglia activation in spinal dorsal horn of rats.

Notoginsenosides， the saponins extracted from Panax notoginseng， have many pharmacological effects， such as anti-inflammation， anti-oxidation， anti-tumor， nervous system and cardiovascular system protection， microcirculation improvement and calcium overload inhibition. At present， notoginsenosides are widely used clinically for treating many diseases with good efficacy， especially for nervous system diseases such as stroke， stroke sequelae and Alzheimer's disease. In recent years， the mechanism underlying their neuroprotective effect has been continuously explored. To advance the applied research on notoginsenosides in the prevention and treatment of central nervous system diseases， this paper， combined with the latest reports， summarizes their neuroprotective effect and mechanisms in terms of regulating voltage-gated ion channels， protecting nerve cells and neurovascular unit， inhibiting oxidative stress and inflammatory reaction， promoting angiogenesis and reducing excitatory neurotoxicity. Although the protective mechanism of notoginsenosides for the nervous system mainly involves the above several aspects， some of them still remain to be fully elucidated， which necessitates the further exploration of neuroprotective effect of notoginsenosides with molecular biology， metabolomics， proteomics and other technologies.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

In order to construct a pichia pastoris expression vector containing the extracellular domain of human Jagged1 and the Fc fragment of human IgG1 fusion gene, or containing only the Fc fragment of human IgG1 and to express them in pichia pastoris. The extracellular domain of human Jagged1 gene was cloned from normal human bone marrow cells. After DNA sequencing, the extracellular domain of Jagged1 gene was inserted into pIC-Fc vector constructed previously, which is Pichia pastoris expression vector containing only the Fc fragment of human IgG1. The constructed plasmid was transformed into yeast GS115 by means of electroporation. The recombinant transformants with a high copy number of the plasmid were selected on MD plate with G418. The expression of protein was induced by addition of methanol. Then, protein expression was analyzed by SDS-PAGE. The results indicated that the extracellular domain of human Jagged1 gene was effectively amplified. The DNA sequencing result showed that the constructed plasmid containing hJagged1(ext)-Fc fusion gene was the same as designed. The fusion protein was successfully expressed in Pichia pastoris. It is concluded that the hJagged1(ext) gene has been successfully cloned and expressed, which provides a new fusion protein for further experiments, the hJagged1(ext)-Fc fusion protein can be used as a new stimulator for proliferation of hematopoietic stem/progenitor cells in vitro.
Calcium-Binding Proteins ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Humans ; Immunoglobulin Fc Fragments ; biosynthesis ; genetics ; Immunoglobulin G ; biosynthesis ; genetics ; Intercellular Signaling Peptides and Proteins ; biosynthesis ; genetics ; Jagged-1 Protein ; Membrane Proteins ; biosynthesis ; genetics ; Pichia ; genetics ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Serrate-Jagged Proteins ; Transfection