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@#In order to explore the therapeutic effects and preliminary mechanism of gypenosides (GP) on hypercholesterolemia, as well as the protective effect on liver injury induced by high-dose simvastatin and high cholesterol diet (HCD), the hypercholesterolemia model of golden hamster was established by high cholesterol diet. The experimental animals were divided into blank group, model group, GP low and high dose groups (60 mg/kg, 120 mg/kg), simvastatin group (10 mg/kg), and GP high dose combined with simvastatin group (120 mg/kg + 10 mg/kg).The efficacy was investigated through dynamic monitoring serum cholesterol and liver function related indexes after drug treatment of 14 and 23 days. The results showed that GP could significantly reduce the levels of serum low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), increase the level of serum high density lipoprotein cholesterol (HDL-C), and reduce the secretion of PCSK9. It is suggested that GP has a good therapeutic effect on HCD diet-induced hypercholesterolemia hamsters, which may be related to its inhibition of PCSK9 secretion. In addition, GP can significantly ameliorate liver damage caused by HCD diet and high-dose simvastatin. These findings provide a scientific basis and useful reference for the combination of GP and statins to reduce toxicity and increase efficacy.
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@#To investigate the mechanism of Shouwu Jiangzhi decoction in treatment of hyperlipidemia by suppress apoB-48 in small intestines, Golden Syrian hamsters were randomly devided into blank group, model group, fenobrate treatment group and Shouwu Jiangzhi decoction treatment group based on weight. The hyperlipidemia models of golden Syrian hamsters were induced by high fat diet(HFD)treatment for 4 weeks, then administered orally with drugs for 4 weeks. The serum indexes of HDL-C, LDL-C, TG and TC were determined by microplate methods, ELISA kits were used to evaluate the contents of serum TNF-α, apoB-48 and FFA. The protein expression levels of p38, ERK, JNK, SREBP, TNF-α and apoB-48 in small intestines were determined by Western blots. The results showed that Shouwu Jiangzhi decoction can effectively increase the serum HDL-C level and reduce the serum level of TG, LDL-C, TNF-α and apoB-48 in HFD-induced hamsters. Furthermore, Shouwu Jiangzhi decoction can significantly downregulate the protein expressions of p38, JNK, ERK, SREBP, TNF-α and apoB-48 in small intestines. Results above indicate that Shouwu Jiangzhi decoction may downregulate the protein expression of apoB-48 to treat hyperlipidemia via partially downregulating TNF-α/MAPK signal pathway.
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Objective To observe the influence of jatrorrhizine on the Akt/AMPK/eNOS signaling pathways and potential protective function in blood vessel of diabetes rats. Methods Male Wistar rats ( n=60) were randomly divided into normal control group, model control group, low-and high dose jatrorrhizine groups. Except normal control group, the other rats were given intraperitoneal injection of STZ after induced insulin resistance, to made typeⅡdiabetes model. CMC-Na solution (5%) was given to normal control and model control group, and the jatrorrhizine resolved in the same solution was administered to low (50 mgkg-1) and high dose (100 mgkg-1) jatrorrhizine groups for 8 weeks. Their body weight, blood glucose, and seruminsulin levels were measured at the end of the treatment, IL-1β, TNF-αlevel in serum were measured by ELISA, and the eNOS, Akt/AMPK protein expression levels in the blood vessel were measured by Western blotting. Results Compared with normal control group, the weight of model control gropwas lossed, blood glucose was increased(P<0.01). Compared with model control group, high-dose jatrorrhizine significantly increased body weight, alleviated blood glucose and decreased serum insulin ( P<0.01) . Serum inflammatory factor like IL-1βwas (92.3±4.3) pgmL-1 in normal control group, (152.4±20.0) pgmL-1 in model control group, (120.96±33.0) pgmL-1 and (95.05±7.7) pgmL-1 in low-and high-dose jatrorrhizine groups, respectively. TNF-αwas (10.50±0.82) pgmL-1 in model control group, (7.48±0.36) pgmL-1 in normal control group, (8.82±0.42) and (7.11±0.33) pgmL-1 in low- and high- dose jatrorrhizine groups, respectively. As compared with control group, eNOS and Akt/AMPK expression in blood vessel was significantly reduced (P<0.05) in model control group, and those were significantly increased in high-dose jatrorrhizine group as compared with model control group ( P<0.05 or P<0.01) . Conclusion Jatrorrhizine may exert protective effect on diabetes mellitus rats through regulating Akt/AMPK/eNOS signaling pathway in blood vessel.
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Objective To observe the influence of jatrorrhizine on the Akt/AMPK/eNOS signaling pathways and potential protective function in blood vessel of diabetes rats. Methods Male Wistar rats ( n=60) were randomly divided into normal control group, model control group, low-and high dose jatrorrhizine groups. Except normal control group, the other rats were given intraperitoneal injection of STZ after induced insulin resistance, to made typeⅡdiabetes model. CMC-Na solution (5%) was given to normal control and model control group, and the jatrorrhizine resolved in the same solution was administered to low (50 mgkg-1) and high dose (100 mgkg-1) jatrorrhizine groups for 8 weeks. Their body weight, blood glucose, and seruminsulin levels were measured at the end of the treatment, IL-1β, TNF-αlevel in serum were measured by ELISA, and the eNOS, Akt/AMPK protein expression levels in the blood vessel were measured by Western blotting. Results Compared with normal control group, the weight of model control gropwas lossed, blood glucose was increased(P<0.01). Compared with model control group, high-dose jatrorrhizine significantly increased body weight, alleviated blood glucose and decreased serum insulin ( P<0.01) . Serum inflammatory factor like IL-1βwas (92.3±4.3) pgmL-1 in normal control group, (152.4±20.0) pgmL-1 in model control group, (120.96±33.0) pgmL-1 and (95.05±7.7) pgmL-1 in low-and high-dose jatrorrhizine groups, respectively. TNF-αwas (10.50±0.82) pgmL-1 in model control group, (7.48±0.36) pgmL-1 in normal control group, (8.82±0.42) and (7.11±0.33) pgmL-1 in low- and high- dose jatrorrhizine groups, respectively. As compared with control group, eNOS and Akt/AMPK expression in blood vessel was significantly reduced (P<0.05) in model control group, and those were significantly increased in high-dose jatrorrhizine group as compared with model control group ( P<0.05 or P<0.01) . Conclusion Jatrorrhizine may exert protective effect on diabetes mellitus rats through regulating Akt/AMPK/eNOS signaling pathway in blood vessel.
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AIM:To select an efficient way of promoting induced pluripotent stem cells ( iPSC) to differentiate into neural stem cells (NSC) by comparing 2 methods.METHODS:The culture system in method A contained SB431542 (5 mmol/L) and drosomophorin (5 mmol/L) with 100%initial cell density, while that in method B contained SB431542 (5 mmol/L) and drosomophorin (1 mmol/L) with 30%~50% initial cell density.For comparison and identification of the 2 methods, the growth state was observed under microscope , and the expression of Pax6, nestin, Sox1 and Sox2 was quantitatively detected by real-time PCR and flow cytometry .The related protein expression and the ability of spontaneous differentiation were determined by immunofluorescence analysis .RESULTS: The cells derived from method A with 5 mmol/L of SB431542 and drosomophorin and 100% initial cell density achieved the higher expression of Pax 6, nestin, Sox1 and Sox2.The growth state was better and the cells differentiated into neurons and astrocytes normally .CONCLU-SION:The method A was superior to method B , and we recommend the method A with 5 mmol/L of SB431542 and droso-mophorin and 100%initial cell density as the method for differentiating NSC .
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<p><b>OBJECTIVE</b>To investigate the potential immunomodulatory properties of fetal bone marrow derived mesenchymal stem cells (FBM- MSCs).</p><p><b>METHODS</b>Mononuclear cells from the bone marrow of second trimester (14-22 wks) fetus were isolated and cultured for the derivation of MSCs. The derived FBM-MSC cells were characterized via morphology, immunophenotyping and the adipogenic and osteogenic differentiation assays. The immunomodulatory properties of FBM-MSC on lymphocytes were evaluated through the co- culture assay with PHA activated adult peripheral blood mononuclear cells (PBMCs).</p><p><b>RESULTS</b>Derived FBM-MSCs were CD29⁺, CD44⁺, CD49e⁺, CD73⁺, CD90⁺, CD105⁺ and CD31⁻ , CD34⁻ , CD45⁻ , HLA-DR⁻ and can be differentiated into adipocytes and osteocytes. When co-cultured with PHA-activated PBMCs, FBM-MSCs inhibited the proliferation of lymphocytes up to 96% and down-regulated the secretion of inflammatory cytokines such as IFN-γ and TNF-α up to 90.9% and 58.4% respectively. When compared with FBM-MSCs cultured alone, the expression of MSCs derived immunomodulatory cytokines, such as IDO, TSG-6 and TGF-β, was up-regulated significantly in the co-culture system.</p><p><b>CONCLUSION</b>MSC derived from fetal bone marrow demonstrated immunosuppressive effects on adult PBMCs in vitro. MSC-derived cytokines like IDO, TSG-6 and TGF-β may be critical for FBM-MSCs mediated immunosuppressive function.</p>
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Adult , Humans , Bone Marrow , Bone Marrow Cells , Cell Biology , Allergy and Immunology , Cell Differentiation , Cell Proliferation , Cells, Cultured , Coculture Techniques , Cytokines , Hematopoietic Stem Cells , Immune Tolerance , Immunophenotyping , In Vitro Techniques , Leukocytes, Mononuclear , Lymphocytes , Mesenchymal Stem Cells , Cell Biology , Allergy and Immunology , OsteogenesisABSTRACT
BACKGROUND:Many studies have showed that neural stem cells therapy is a new strategy for hypoxic-ischemic encephalopathy. OBJECTIVE:To review and analyze the status of research, transplantation strategies and mechanism of neural stem cells therapy for treatment of hypoxic-ischemic encephalopathy. METHODS:A computer-based retrieval was performed in PubMed and CNKI database to search papers published from August 2000 to August 2013 using the key words of“hypoxic-ischemic encephalopathy, neural stem cells”in English and Chinese. The papers with objective-independent and repetitive contents were excluded, and final y 39 papers were included for final analysis. RESULTS AND CONCLUSION:Neural stem celltransplantation can promote recovery of neurological function, which brings new hope to hypoxic-ischemic encephalopathy patients. But the study is at a primary stage and limited in laboratory. There are many critical factors that hinder the clinical transplantation, such as delivery path, transplantation time, single or combined transplantation, mechanisms of action. Application of neural stem cells requires further investigation.
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Purpose To observe the protective effects of low molecular hirudo peptides on focal cerebral ischemia reperfusion injury in rats and to explore its possible mechanism. Methods Middle cerebral artery occlusion (MCAO) was used to prepare focal cerebral ischemia and the neurological scores and infarction area of brain slices, and water content of brains were assessed. Superoxide dismustase (SOD) activity and malondi-aldehyde ( MDA) content in homogenate of ischemic brain tissue were determined by spectrophotometric assay. Results Hirudo peptides could reduce the percentage of infarction area and the water content in the cerebral hemisphere, increase SOD activity and decrease MDA content in ischemic brain tissue. Conclusion Low molecular hirudo peptides have protective effects on focal cerebral ischemia injury, and its mechanism may be related to the antioxidant action.
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Objective Delayed xenograft rejection (DXR) is a major barrier to the long-term xenograft survial.This study evaluated the interaction between human peripheral blood mononuelear cells (PBMC) and porcine endothelial cells (PEC),and the effects of new generation of rabbit antihuman leukocyte polyclonal antibody (newRALG) inhibiting xenogeneic cell-mediated immune responses.Methods newRALG was obtained from rabbits after immunization with activated lymphocytes and monoeytes.PEC were isolated from aorta,and human PBMC were isolated from peripheral blood.Co-cultures of PKH-26 labeled PEC with PBMC were established,newRALG,thymoglobulin,isotype Ig and scavenger receptor (SR) ligand poly G were added into the co-cultures.Cells were collected,then FACS analysis was carried out to detect the up-take of PEC membrane by monocytes and the expression of costimulatory molecules.Lymphocyte proliferative responses to PEC with or without antibody were evaluated by a xenogeneie mixed lymphocyte-endothelial cell reaction (xMLER).Results FACS analysis revealed that monocytes from PBMC-PEC co-cultures became positive for PKH-26 following their interaction with PKH-26 labeled PEC,indicating that they engulfed PEC membranes during activation.PKH-26 positive monocytes up-regulated the CD40 and CD80 expression.Furthermore,SR blockade with poly-G prevented PEC membrane up-take by monocytes,newRALG greatly reduced SR-mediated PEC membrane up-take.The effects of thymoglobulin in inhibiting PEC membrane uptake were limited.xMLER demonstrated strong lymphocyte proliferation in response to PEC,and lymphocyte proliferation was dramatically inhibited by newRALG but not isotype Ig at a dosmdependent manner.Conclusions Monocytes play an important role in xenogeneic immune responses.SR ligand poly G inhibits PEC membrane up-take.newRALG inhibits PEC membrane up-take by monocytes,suggesting that newRALG blocks SR.Additionally,newRALG inhibits lymphocyte proliferation in response to PEC.These results suggest that this new polyclonal preparation may thus impair the initiation of xeno-specific immune responses and prevent xenograft rejection.
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Objective To explore the expression and the role of monocyte-derived costimulatory molecuels during xenogeneic immune responses. Methods Porcine endothelial cells (PEC) were isolated from aorta, and subcultures were performed. CD4+ cells and monocytes were purified from human peripheral blood mononuclear cells (PBMC). PBMC-PEC co-cultures were established, and the cells were collected followed by staining with florescent-labeled monoclonal antibodies and analyzing by FACS. In selected experiments, monoclonal antibodies specific for CD154, CD80 and CD86 were added into PBMC-PEC co-cultures, and the effects of co-stimulatory molecule blockade in inhibiting lymphocyte proliferation in response to PEC were determined by 3H-thymidine up-take. The proliferation of CD4+ cells induced by PEC-conditioned monocytes with or without co-stimulation blockade was evaluated. Results PBMC-PEC co-incubation demonstrated dramatic lymphocyte proliferation as determined by 3H-thymidine up-take. FACS found that resting monocytes expressed only CD86 but not CD40 and CD80. CD14+ monocytes from PEC-stimulated PBMC demonstrated up-regulation of CD80 and CD40 expression. The up-regulation of CD86 was revealed. PEC-activated monocytes induced CD4+ cell proliferation while resting monocytes did not and this proliferation was inhibited by anti-CD154, anti-CD80 or anti-CD86 antibodies. Conclusions CD14+ monocytes play an important role during xenogeneie immune responses in indirect antigen presentation and co-stimulation- The interaction between monocyte-derived co-stimulatory molecules and CD4+ cell-derived CD154 and CD28 delivers secondary signal and induces CD4+ proliferation, and the co-stimulation blockade inhibits xe-nogeneic cell-mediated immune responses.
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Objective To investigate the relationships of the serum level of interleukin-1β(IL-1β), the single nucleotide polymorphism(SNP) of IL-1B and interleukin-1 receptor antagonist (IL-1RN) genes with the gastric cancer or the gastric cancer infected by Helicobacter pylori(Hp). Methods The SNP of the IL-1B(-31C/T and -511C/T) was determined by gene chip and the variable number of tandem repeat(VNTR) of IL-1RN were detected by agarose gel electrophoresis. The sera level of IL-1β and the concentrations of IgG, IgM and IgA of Hp antibodies were measured by ELISA. Results The serum level of IL-1β increased significantly in patients with gastric cancer than that in control group(P<0.001). Hp infection was detected in 69.2% of 260 patients and 46.5% of 284 controls[P<0.001, odds ratio (OR)=2.59]. Frequency of genotype IL-1B-31TT or IL-1B-511TT in patients with gastric cancer were significantly higher than that in healthy controls (P<0.01, OR=1.95; P<0.05, OR=1.62), respectively. Frequency in Hp+ gastric cancer group was higher than that in Hp- group (P<0.05, OR= 2.00), and frequency of haplotype T-T in patients group was significantly higher than that in healthy control(χ2=4.45, P<0.05). The serum level [(802±148) ng/L] of IL-1β of the gastric cancer group was significantly higher than that of the control group [ (501±125) ng/L, P<0.01]. The serum level of IL-1β in patients with -31T or -511T allele was (845±156) ng/L or (871±148) ng/L, significantly higher than that without -31T [(555±116) ng/L] and -511T allele [(581±128) ng/L]. Furthermore, The serum level of IL-1β in Hp+ group with T allele were significantly higher than that in Hp- group (P<0.001). There was no association of IL-1RN gene and other IL-1B gene with gastric cancer or Hp+ gastric cancer. Conclusion IL-1B-31TT genotype was related to gastric cancer. IL-1B-511TT genotype was related to gastric cancer or with Hp+ gastric cancer. Both IL-1B-31T and -511T are associated with IL-1B gene. The haplotype T-T may be the genetic susceptible factor to gastric cancer.
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0.10). Conclusions HLA-B51 might be a susceptible gene for BD, and there was a weak association between HLA-B51(HLA-B*5101) and BD patients with uveitis.
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Objective: To investigate the apoptosis-inducing effect of arsenic trioxide (As2O3) on gastric carcinoma cell line AGS in vitro and to assess the influence of As2O3 on the expression of signal transducers and activators of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF). Methods: AGS cells were treated with different concentrations of As2O3 (1, 5, and 10 ?mol/L) for 24,48, and 72 h. The cell proliferation was detected by MTT assay, cell apoptosis and cell cycle distribution were measured by flow cytometry and TUNEL, and the expression of STAT3 and VEGF was investigated by ELISA, immunohistochemistry and real-time PCR. Results: (1) As2O3 inhibited AGS cell proliferation in a time- and dose-dependent manner; (2) FCM results showed a typical sub-diploid peak before G0/ G1 phase and cell cycle analysis showed G2/M phase arrest; (3) TUNEL analysis revealed the DNA fragmentation; (4) During the As2O3-induced apoptosis of AGS cells, the expression of STAT3 and VEGF was down-regulated, especially when As2O3 was at 10 mol/L. Conclusion: As2O3 can inhibit the proliferation of AGS cells and induce AGS cell apoptosis, which might be related with cell cycle block and down-regulation of STAT3 and VEGF expression.