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The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.
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Humans , Ischemic Stroke , Chemokine CXCL12 , Acupuncture Therapy , Mesenchymal Stem Cells , InflammationABSTRACT
Objective@#To prepare a composite membrane by chitosan/β-sodium glycerophosphate(CS/β-GP) thermosensitive hydrogel combined with stromal cell derived factor-1(SDF-1) and observe its biological characteristics in vitro.@*Methods@#Different doses of SDF-1 were added into CS/β-GP solution and then the thermosensitive gel time was measured. The SDF-1/CS/β-GP solution was membrane paved and dried to prepare composite membranes. The morphological characteristics were observed by scanning electron microscope(SEM). Composite membranes were placed into cell culture medium, and the supernatant(n=3) was extracted after standing at 6, 12, 24, 36, 48, 60 h, respectively. The concentration of SDF-1 in the solution was measured. Bone mesenchymal stem cells(BMSCs) were cultured in the Transwell room, and the composite membranes containing different concentrations of SDF-1 were placed in the lower chamber. There were four groups(n=3): Group M0 used CS/β-GP membrane(control group), Group M1, M2, M3 used SDF-1/CS/β-GP membrane(SDF-1 was 100, 200, 400 ng/mL respectively). After culture for 6, 12 and 24 h, the cells under the membrane were preserved and Giemsa stained and counted. The absorbance(OD) value was measured by MTT method to calculate the cell proliferation rate. SPSS 19.0 was used for multi-factor analysis of variance.@*Results @#After adding a certain amount of SDF-1 into CS/β-GP solution, the gel time did not change significantly(P>0.05). The SDF-1/CS/β-GP membrane was translucent and porous at 37 ℃. In this experiment, the volumic mass of SDF-1 released by SDF-1/CS/β-GP composite membrane increased gradually with the experimental time(P<0.01). Transwell cell chemotaxis test showed that the number of BMSCs cells with directional migration increased with the prolongation of observation time(P<0.01) and the increase of SDF-1 volumic mass(P<0.01). In MTT test, the OD value of migration cell solution increased with the prolongation of time(P<0.01) and the increase of SDF-1 volumic mass(P<0.01). @*Conclusion@# The SDF-1/CS/β-GP composite membrane has a porous structure and biological activity of chemotactic BMSCs directional migration. It is a potential membrane for guided tissue regeneration.
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OBJECTIVE To investigate the effects and mechanism of atractylodin on inflammatory injury of periodontal tissue and alveolar bone loss in periodontitis rats. METHODS A total of 144 SD rats were divided into control group （intragastric and intraperitoneal injection of normal saline）， model group （intragastric and intraperitoneal injection of normal saline）， atractylodin low-dose， medium-dose and high-dose groups （intraperitoneal injection of 6.665， 13.33， and 26.66 mg/kg atractylodin）， metronidazole group （positive control group， intragastric injection of 0.05 g/kg metronidazole， intraperitoneal injection of normal saline）， AMD3100 [stromal cell-derived factor-1 （SDF-1）/CXC chemokine receptor-4 （CXCR4） pathway inhibitor] group （intragastric injection of 1 mg/kg AMD3100， intraperitoneal injection of normal saline）， atractylodin high-dose+AMD 3100 group （intraperitoneal injection of 26.66 mg/kg atractylodin， intragastric injection of 1 mg/kg AMD3100）， with 18 rats in each group. Except for the control group， all other groups of rats were inoculated with Porphyromonas gingivalis to construct a periodontitis model. After successful modeling， they were given relevant medicine or normal saline， once a day， for 4 consecutive weeks. The gingival index of rats was detected； the levels of interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） in rat serum were also determined； alveolar bone resorption， periodontal histopathologic changes and the number of osteoclasts were detected by methylene blue staining， HE staining and TRAP staining， respectively. The expressions of osteoprotegerin （OPG）， receptor activator of NF-κB ligand （RANKL）， SDF-1 and CXCR4 proteins were determined. RESULTS Compared with the control group， serious pathological injury of periodontal tissue was found in the model group， the gingival index， the levels of IL-6 and TNF- α， alveolar bone absorption value， the number of osteoclasts， and the expression of RANKL protein were all increased significantly （P＜0.05）， while the expressions of OPG， SDF-1 and CXCR4 proteins were decreased significantly （P＜0.05）. Compared with the model group， pathological injury of periodontal tissue in rats was reduced； the gingival index， the levels of IL-6 and TNF-α， alveolar bone resorption value， osteoclast number and RANKL protein expression were decreased significantly， while protein expressions of OPG， SDF-1 and CXCR4 were increased significantly in atractylodin low-dose， medium-dose and high-dose groups and metronidazole group （P＜0.05）. The change trend of corresponding indexes in the AMD3100 group was opposite to the above （P＜0.05）. AMD3100 attenuated the inhibitory effect of high-dose atractylodin on inflammatory response and alveolar bone loss in rats with periodontitis （P＜0.05）. CONCLUSIONS Atractylodin may improve the inflammatory response and alveolar bone loss in periodontitis rats by activating the SDF-1/CXCR4 signaling pathway.
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Objective:To explore the possible mechanism of Astragali Radix-Curcumae Rhizoma （AC） in inhibiting tumor growth in the orthotopic transplantation model of colon cancer in mice. Method:The molecular docking technology was used to predict the intermolecular interaction between the main active components of AC and the pathway target proteins， such as stromal cell-derived factor-1 （SDF-1）， C-X-C motif chemokine receptor 4 （CXCR4）， and nuclear factor kappa-B p65 （NF-<italic>κ</italic>B p65）. The orthotopic transplantation model of CT26.WT colon cancer was established in mice for <italic>in vivo</italic> experimental verification. Sixty BALB/c male mice were randomly divided into a sham operation group， a model group， a 5-fluorouracil （5-Fu， 30 mg·kg<sup>-1</sup>） group，and low- （0.32 g·kg<sup>-1</sup>）， medium- （0.64 g·kg<sup>-1</sup>）， and high-dose （1.28 g·kg<sup>-1</sup>） AC groups， with 10 mice in each group. The sham operation group and the model group received normal saline by gavage. The corresponding drugs were administered by gavage in the 5-Fu group and by intraperitoneal injection in the AC groups. After intervention for 15 days， the tumor <italic>in situ</italic> was completely stripped， and the colon tissues 5-6 cm in length adjacent to the tumor were taken. The tumor volume was measured and calculated. The pathological changes of tumor tissues and colon tissues were observed by Hematoxylin-Eosin （HE） staining. Western blot was used to detect the protein expression of SDF-1， CXCR4， p-NF-<italic>κ</italic>B p65 in colon tissues. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect SDF-1， CXCR4， NF-<italic>κ</italic>B p65， Cyclin D<sub>1</sub>， oncogene c-Myc protein and mRNA expression in tumor tissues. Result:Compared with the model group， 5-Fu and AC groups showed reduced tumor volumes <italic>in situ</italic> （<italic>P</italic><0.05， <italic>P</italic><0.01）， with the tumor inhibition rate in the 5-Fu group as high as （61.38±2.34）%. The tumor-inhibiting effect was optimal in the medium-dose AC group， with the tumor inhibition rate of （43.43±3.71）%. Compared with the model group， 5-Fu and AC groups showed relieved pathological changes of tumor and colon tissues. Specifically， AC down-regulated the protein expression levels of SDF-1， CXCR4， and p-NF-<italic>κ</italic>B p65 in colon tissues （<italic>P</italic><0.01）， and down-regulated the protein and mRNA expression levels of SDF-1， CXCR4， NF-<italic>κ</italic>B p65， Cyclin D<sub>1</sub>， and c-Myc in tumor tissues （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:AC can inhibit the growth of orthotopic transplantation tumor of colon cancer， and its intervention mechanism may be related to the regulation of related protein and mRNA expression in the SDF-1/CXCR4/NF-<italic>κ</italic>B signaling pathway.
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Objective:To investigate the effect of Qixian Tongluo prescription on neural function recovery in patients with cerebral infarction and its mechanism. Method:A total of 100 inpatients （January to June，2020）with cerebral infarction in the Neurology Department of Wenzhou Hospital of Traditional Chinese Medicine were assigned to an experimental group （<italic>n</italic>=50） and a control group （<italic>n</italic>=50） according to the random number table. Both groups received conventional treatment of western medicine，while the experimental group took additional Qixian Tongluo prescription. Treatment lasted for 12 weeks. The clinical efficacy，National Institutes of Health Stroke Scale （NIHSS） score， the modified Barthel index （MBI），Fugl-Meyer assessment （FMA） score， and levels of brain-derived neurotrophic factor（BDNF），vascular endothelial growth factor（VEGF）， and stromal cell-derived factor-1（SDF-1） in peripheral blood of the two groups before and after treatment were compared. Result:The total response rate in the experimental group was 84.00%（42/50），higher than 66.00%（33/50） in the control group （<italic>Z</italic>=-7.365，<italic>P</italic><0.05）. There was no significant difference in the scores of MBI，FMA， and NIHSS before treatment between the two groups. The MBI and FMA scores of the two groups increased （<italic>P</italic><0.01）， and the NIHSS scores decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the control group after treatment， the experimental group showed increased MBI and FMA scores and decreased NIHSS score （<italic>P</italic><0.05）. There was no significant difference in BDNF level between the two groups before and after treatment. The VEGF and SDF-1 levels in the peripheral blood of the two groups were higher than those before treatment （<italic>P</italic><0.05）， and the experimental group was higher than the control group （<italic>P</italic><0.05）. Conclusion:Qixian Tongluo prescription can effectively improve the clinical efficacy，the quality of life， and the prognosis of patients with cerebral infarction during convalescence. The underlying mechanism is associated with the promotion of the expression of endogenous VEGF and SDF-1 in the peripheral blood to activate the SDF-1/chemokine receptor 4（CXCR4） signaling pathway， induce the recruitment and mobilization of endothelial progenitor cells， and facilitate the angiogenesis and repair of ischemic brain tissues.
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BACKGROUND: Anti-tuberculous chemotherapy is the main method for treating bone and joint tuberculosis. However, systemic administration hardly maintains the effective drug concentration in the focus area, and the therapeutic efficacy is unsatisfactory. OBJECTIVE: To prepare a chitosan-gelatin/poly(lactic-co-glycolic acid) combined with drug-loaded hydrogel, which can release anti-tuberculosis drugs in situ for a long time and promote osteogenesis. METHODS: Isoniazid, a hydrophilic anti-tuberculosis drug, and a hydrophobic stromal cell derived factor-1 were loaded into poly(lactic-co-glycolic acid) by double emulsion method to prepare drug-loaded poly(lactic acid co-glycolic acid) microspheres, which were then mixed into chitosan gelatin/poly(lactic acid co-glycolic acid) combined with drug-loaded hydrogel. The ability of drug delivery and anti-tuberculosis of poly(lactic acid co-glycolic acid) microspheres and chitosan gelatin/poly(lactic acid co-glycolic acid) combined with drug-loaded hydrogels in vitro were tested. MC3T3-E1 cells were inoculated on the surface of microspheres and hydrogel respectively. The biocompatibility was detected by cell counting kit-8 assay. The osteogenetic activity was detected by alkaline phosphatase activity. RESULTS AND CONCLUSION: (1) The burst release of isoniazid in the microspheres was about 23.3% in 1 hour, 42.6% in 2 days, and then it entered the sustained-release stage in the later 25 days. The burst release of stromal cell derived factor was about 19.8% in 1 hour, 44.7% in 2 days, and then it entered the sustained-release stage in the next 25 days. The release of isoniazid and stromal cell-derived factor in the combined drug-loaded hydrogel was 8.3% and 8.5% in the first hour, respectively. The cumulative release rates on the second day were 15.2% and 17.6%, respectively, which were much lower than that of poly(lactic acid co-glycolic acid) microspheres. (2) After 4 weeks in vitro, the antibacterial diameter of the combined drug-loaded hydrogel was much larger than that of the drug-loaded microspheres, and the antibacterial rate was higher than that of the drug-loaded microspheres (P < 0.05). (3) The combined drug-loaded hydrogel and the drug-loaded microspheres had good cytocompatibility and cell viability was about 100%. (4) After 5 and 10 days of culture, there was no significant difference in the activity of alkaline phosphatase on the surface of drug-loaded hydrogel and drug-loaded microspheres. (5) These results show that the in situ chitosan-gelatin/poly(lactic acid co-glycolic acid) combined with drug-loaded hydrogel can be used for treating tuberculosis and other bone and joint infections.
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@#AIM: To investigate the expression and significance of stromal cell-derived factor(SDF-1)and its receptor CXC chemokine receptor 4(CXCR4)in patients with pterygium of different ages.<p>METHODS: From January 2018 to October 2018, surgical specimens of 60 patients with primary pterygium and 60 eyes(including 30 eyes younger than 50 years old and 30 eyes older than 50 years old)were collected from the No.474 Hospital of Chinese PLA, at the same time collect age matched strabismus diorthosis and normal conjunctiva tissues of 30 patients with retinal detachment repairs(including 15 eyes younger than 50 years, older than 50 years of age 15 eyes).The expression and localization of SDF-1/CXCR4 in pterygium tissue specimens were detected by HE staining and immunohistochemistry, and the relationship between the expression of SDF-1/CXCR4 and the clinical characteristics of patients was analyzed. The mean optical density of SDF-1 /CXCR4 was measured by IPP 6.0 software.<p>RESULTS: SDF-1/CXCR4 showed slightly positive or no positive expression in normal conjunctival basal cells, but positive expression in both full-layer conjunctival epithelial cells and vascular endothelial cells in pterygium, with significant difference in expression level, and more obvious expression in basal cells, showing obvious polarity. The expression levels of SDF-1 and CXCR4 in pterygium tissues were higher than those in normal conjunctival tissues, and the difference was statistically significant(<i>P</i><0.05). The expression of CXCR4 in patients younger than 50 years old was greater than that in patients older than 50 years old, and the difference was statistically significant(<i>P</i><0.05).<p>CONCLUSION: SDF-1 and CXCR4 expression is up-regulated in pterygium, suggesting that SDF-1 and CXCR4 participates in the formation of pterygium and inhibits the SDF-1/CXCR4 signaling pathway, which may inhibit the occurrence of pterygium, and may also become a drug therapeutic target for pterygium, and become a new research direction. The higher expression of CXCR4 in young pterygium patients suggests that individualized drug administration may be realized in the future to reduce the waste of medical resources.
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Objective::To observe the clinical efficacy of Duhuo Xuduan Tang for oral administration and iontophoresis in the treatment of knee osteoarthritis (KOA) with liver and kidney deficiency and its effect on stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling pathway. Method::Totally 150 KOA patients with deficiency of liver and kidney diagnosed in the Teaching Hospital of Tianjin University of Traditional Chinese Medicine(TCM) were randomly divided into control group, oral TCM group and iontophoresis group, with 50 cases in each group. The control group was given glucosamine sulfate capsule, 0.5 g/time, twice a day, while the oral TCM group was given Duhuo Xuduan Tang, 150 mL/time, twice a day. In the iontophoresis group, Duhuo Xuduan Tang was administered at Kuangu acupoint, Xiguan acupoint, Xiyan acupoint and Dubi acupoint for iontophoresis for 30 minutes, once a day. All of the three groups were treated for 4 weeks. The swelling degree and the pain degree of knee joint before and after treatment were observed, and the clinical efficacy was recorded. The protein contents of SDF-1, CXCR4, matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13) in knee joint fluid before and after treatment were detected by enzyme-linked immunosorbent assay (ELISA). Result::The efficacy of oral TCM group was better than that of iontophoresis group and control group, and the recurrence rate was the lowest (P<0.05). Compared with before treatment, the tenderness increased, whereas visual analogue scale(VAS) score, knee swelling score, The Western Ontario and McMaste Universities (WOMAC) score and SDF-1, CXCR4, MMP-3 and MMP-13 protein content in knee joint fluid decreased in oral TCM group after treatment, which were better than those in iontophoresis group and control group (P<0.05). Conclusion::Duhuo Xuduan Tang for oral administration and iontophoresis has an obvious effect on KOA with liver and kidney deficiency, with the best effect through oral administration. Its mechanism may be related to the inhibition of SDF-1/CXCR4 inflammatory signaling pathway and cartilage decomposition.
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Objective:To investigate the effect of Ru′ai Shuhou prescription （RSR） drug-containing serum on the proliferation and invasion ability of breast cancer cells MDA-MB-453 based on the biological axis of stromal cell-derived factor-1（SDF-1）/chemokine receptor 4 （CXCR4）. Method:A model of MDA-MB-453 cells with SDF-1-induced high expression of CXCR4 was established， and the rat drug-serum containing RSR and blank rat serum were prepared respectively. The cells were divided into fetal bovine serum control group （Blank）， blank rat serum group， SDF-1+blank rat serum group， SDF-1+RSR group， AMD3100+ SDF-1+blank rat serum group， and AMD3100+ SDF-1+RSR group. After intervention for 48 h， cell proliferation was detected by cell counting kit-8 （CCK-8） assay， cell invasion ability was detected by transwell assay， and mRNA and protein expressions of CXCR4， matrix metalloproteinase-2 （MMP-2） and MMP-9 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. Result:As compared with the blank serum group， the proliferation of MDA-MB-453 cells was promoted and expression of CXCR4 mRNA was increased significantly when SDF-1 was 100 μg·L-1 （P<0.05）. As compared with SDF-1+blank rat serum group， RSR inhibited the proliferation and invasion of MDA-MB-453 cells induced by SDF-1， and at the same time， down-regulated the mRNA and protein expressions of CXCR4， MMP-2 and MMP-9 （P<0.05）. After pre-treatment with AMD3100 for 24 h， the inhibitory effect of RSR to cell proliferation was significantly increased （P<0.05）， and meanwhile， the decreases in mRNA and protein expression of CXCR4， MMP-2 and MMP-9 were more obvious， with statistically significant differences （P<0.05）. Conclusion:Through SDF-1/CXCR4 biological axis， RSR could down-regulate the expression of MMP-2 and MMP-9， reduce the degradation of extracellular matrix （ECM）， and then inhibit the metastasis of MDA-MB-453 cells. In addition， it has a synergistic effect with CXCR4 inhibitor AMD3100.
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Objective: To explored the effect of stromal cell-derived factor 1α (SDF-1α) on promoting the migration ability of rat adipose derived stem cells (rADSCs) by constructed the rADSCs overexpression SDF-1α via adenovirus transfection. Methods: rADSCs were isolated from adipose tissue of 6-week-old SPF Sprague Dawley rats. Morphological observation, multi-directional differentiations (osteogenic, adipogenic, and chondrogenic inductions), and flow cytometry identification were performed. Transwell cell migration experiment was used to observe and screen the optimal concentration of exogenous SDF-1α to optimize the migration ability of rADSCs; the optimal multiplicity of infection (MOI) of rADSCs was screened by observing the cell status and fluorescence expression after transfection. Then the third generation of rADSCs were divided into 4 groups: group A was pure rADSCs; group B was rADSCs co-cultured with SDF-1α at the best concentration; group C was rADSCs infected with recombinant adenovirus-mediated green fluorescent protein (Adv-GFP) with the best MOI; group D was rADSCs infected with Adv-GFP-SDF-1α overexpression adenovirus with the best MOI. Cell counting kit 8 (CCK-8) and Transwell cell migration experiment were preformed to detect and compare the effect of exogenous SDF-1α and SDF-1α overexpression on the proliferation and migration ability of rADSCs. Results: The cell morphology, multi-directional differentiations, and flow cytometry identification showed that the cultured cells were rADSCs. After screening, the optimal stimulating concentration of exogenous SDF-1α was 12.5 nmol/L; the optimal MOI of Adv-GFP adenovirus was 200; the optimal MOI of Adv-GFP-SDF-1α overexpression adenovirus was 400. CCK-8 method and Transwell cell migration experiment showed that compared with groups A and C, groups B and D could significantly improve the proliferation and migration of rADSCs ( P<0.05); the effect of group D on enhancing the migration of rADSCs was weaker than that of group B, but the effect of promoting the proliferation of rADSCs was stronger than that of group D ( P<0.05). Conclusion: SDF-1α overexpression modification on rADSCs can significantly promote the proliferation and migration ability, which may be a potential method to optimize the application of ADSCs in tissue regeneration and wound repair.
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@#AIM:To discuss the effect of ranibizumab combined with vitrectomy(VT)on the serum vascular endothelial growth factor A(VEGF-A)and human stromal cell derived factor 1(SDF-1)expression in patients with PDR.<p>METHODS: Totally 120 patients with PDR were selected from January 2017 to January 2018 in our hospital, according to the random digital table, they were divided into group A and group B, 60 cases in each group, group A was given VT treatment, group B was given ranibizumab vitreous injection treatment on this basis, the VT operation, complication and VEGF-A, SDF-1, BCVA, CMT were compared between the two groups.<p>RESULTS: The postoperative serum VEGF-A and SDF-1 levels in the two groups were significantly lower than those in the preoperative, and the group B was significantly lower than group A(<i>P</i><0.05). The VT operation time, electrocoagulation, intraoperative bleeding and complication rate in the group B were significantly lower than those in the group A(<i>P</i><0.05). The 1d, 3mo postoperative BCVA, CMT in the two groups were significantly lower than those in the preoperative, and the group B was significantly lower than the group A(<i>P</i><0.05).<p>CONCLUSION: ranibizumab combined with VT can effectively improve the serum VEGF-A and SDF-1 levels in patients with PDR, it can reduce the trauma and complications of VT, and improve the BCVA and CMT in patient.
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Objective To explore the mechanism by which specific agonist of farnesoid X receptor (FXR) GW4064 inhibits the growth and invasion of colon cancer cells. Methods Human colon cancer cell lines HT-29 were in vitro cultured. After treatment with GW4064 of 0, 0.1, 1, 3, 5, 7 and 10 μmol/L for 72 h, cell viability was measured by MTT assay. After treatment with GW4064 of 0, 1 and 5 μmol/L for 24 h, the cell morphology was observed under phase contrast microscope, and the mRNA expression levels of FXR and stromal cell-derived factor 1 (SDF-1) were detected by PCR. After treatment with GW4064 of 0 and 1 μmol/L for 24 h, the cell invasive ability was detected by cell scratch test. After treatment with GW4064 of 0, 1, 5 and 7 μmol/L for 24 h, the SDF-1 expression in the culture medium was detected by ELISA. Nude mouse. tumorigenesis model was established by subcutaneous inoculation of HT-29 cells. After intragastric administration with GW4064 or DMSO for 16 d, the tumor growth and the mRNA expression of FXR and SDF-1 in the tumors were determined. ResultsGW4064 inhibited the growth of HT-29 cells in a dose-dependent manner, and there was significant difference in the cell viability of HT-29 cells between the GW4064 groups (1, 3, 5, 7 and 10 μmol/L) and the control group (0 μmol/L, all P<0.05). After treatment with GW4064, phase contrast microscopy showed contracted and rounded colon cancer cells and slender cells transforming into epidermoid cells. The cell scratch test showed that the invasion ability of the colon cancer cells was significantly reduced after treatment with GW4064 compared with the control group (0 μmol/L, P<0.05). PCR results showed that the mRNA expression level of FXR was increased in a dose-dependent manner after GW4064 treatment, while the expression of SDF-1 mRNA changed in the opposite way. ELISA results showed that the SDF-1 expression in the cell culture supernant was decreased with the increase of GW4064 concentrations, and there were significant differences between the GW4064 (1, 5 and 7 μmol/L) groups and the control group (0 μmol/L, P<0.05). GW4064 significantly reduced tumor size compared with the control group (DMSO, P<0.05). In addition, the mRNA expression of FXR in the tumors was increased, and the mRNA expression of SDF-1 was decreased. ConclusionThe activation of FXR can inhibit the invasive growth of colon cancer cells and the expression of SDF-1.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui" (GV20) and "Zusanli" (ST36) on the expression of stromal cell derived factor-1α (SDF-1α) and CD34 in ischemic cortex tissue of cerebral ische-mia /reperfusion injury (CI/RI) rats, so as to study its mechanisms underlying improving CI/RI. METHODS: Thirty male SD rats were equally and randomly divided into sham operation, model and EA groups (n=10 rats in each group). The CI/RI model was established by occlusion of the middle cerebral artery for 120 min, followed by reperfusion. EA (40 Hz, 1-2 mA) was applied to GV20 and left ST36 for 20 min, once daily for successive 14 days. The neurological deficit severity was assessed by using Longa's and colleagues' methods. The histopathological changes of the ischemic tissues were observed after H.E. staining and the expression of SDF-1α and CD34 in the ischemic cortex tissues was detected by immunohistochemistry. RESULTS: After modeling, the neurological deficit score, and the numbers of SDF-1α and CD34-positive cells in the ischemic cerebral cortex tissue were significantly increased in the model group (P<0.05). Following EA intervention, the increased neurological deficit score was reversed at the 3rd, 7th and 14th day, and the increased SDF-1α and CD34-positive cells were significantly further up-regulated in the EA group (P<0.05). H.E. staining showed tissue edema, widening of the intercellular space, cavitation-like changes, neuronal shrinkage, nuclear pyknosis with hyperchroma or even disappearance, and aggregation of inflammatory and neurogliocytes in the model group. These situations were relatively milder in the EA group. CONCLUSION: EA of GV20 and ST36 can improve neurological function of CI/RI rats, which may be associated with its effect in up-regulating the expression of SDF-1α and CD34 proteins in the ischemic cerebral cortex tissues.
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Objective@#To investigate the expression of miRNA-1 (miR-1) in colorectal cancer (CRC) tissues and its effect on proliferation and invasion of CRC cells in vitro as well as its mechanism.@*Methods@#A total of 180 CRC tissues from the hospitalized patients who underwent excision surgery and 114 adjacent cancer tissues in the Affiliated Cancer Hospital of Shanxi Medical University between June 2015 and December 2015 were collected. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-1 in 58 cases of CRC tissues and adjacent cancer tissues. Immunohistochemistry was used to detect the expression of stromal cell-derived factor-1 (SDF-1) protein in 122 CRC tissues and effect of overexpression or knockdown of miR-1 on the proliferation, colony formation and invasiveness of DLD1 cells, respectively. Western blot was used to determine the effect of overexpression or knockdown of miR-1 on the expression of SDF-1 in DLD1 cells.@*Results@#RT-qPCR results showed that the expression of miR-1 in CRC tissues was decreased compared with the corresponding adjacent cancer tissues (the relative expression level ratio < 0.5), and the low expression rate of miR-1 in CRC was 82.8% (48/58). Immunohistochemistry results showed that the positive expression rate of SDF-1 in CRC tissues was higher than that in adjacent cancer tissues [81.1% (99/122) vs. 8.9% (5/56), χ2 = 82.415, P < 0.01]. Cell function experiment showed that, compared with the control group, the proliferative activity of DLD1 cells that transfected miR-1 mimics was decreased, meanwhile, the colony formation, invasion and SDF-1 expression were reduced (P < 0.05). The proliferative activity, colony formation, invasion and SDF-1 expression in DLD1 cells that transfected miR-1 inhibitor were improved compared with those in the control group (P < 0.05).@*Conclusions@#The expression of miR-1 in CRC tissues is low and it may act as a tumor suppressor gene through affecting proliferation and invasive potential of CRC cells by regulating the expression of SDF-1.
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Objective To investigate the effect of alogliptin on albuminuria in patients with early type 2 diabetic kidney disease (DKD) and the related mechanism.Methods One hundred patients with early DKD admitted in our hospital from May 2016 to May 2017 were randomly divided into two groups with 50 cases in each group.Patients in the control group were given metformin and gliclazide,while those in study group were given metformin and alogliptin,the treatment lasted for 24 weeks.The changes of urinary albumin-to-creatinine ratio (UACR),stromal cell-derived factor-1α (SDF-1α) and the fasting plasma glucose (FPG),2-h postprandial plasma glucose (2 hPPG),glycosylated hemoglobin(HbA1c) were measured before and after the treatment in two groups.Results There were no significant differences in HbA1c [(8.17± 0.46)％ vs.(8.29±0.48)％],UACR[(109±53) vs.(105±48)mg/g],SDF-1α [(1.21±0.3 9) vs.(1.17±0.35)μg/L] levels before treatment between two groups (t=0.343,0.464,0.075,all P＞0.05).After treatment,the HbA1c levels were significantly decreased in both groups (t=2.293,2.302,all P=0.03) and there was no significant difference between two groups[(6.82±0.75)％ vs.(6.93 ±0.79)％,t=0.295,P=0.77];the UACR levels were significantly reduced in both groups,but the level of study group was significantly lower than that of control group [(82±38) vs.(94±47) mg/g,t=3.320,P＜0.01];the SDF-1α levels were significantly increased in both groups,but the level of study group was significantly higher than that of control group[(3.01 ±0.38) vs.(2.76±0.42)μg/L,t=5.474,P＜0.01].There was no significant difference in the incidence of adverse reactions between the two groups [13％ (6/46) vs.12％ (6/48),x2=0.002,P＞0.05].Conclusion Alogliptin can effectively control the blood glucose,reduce urine albumin excretion and protect renal function in patients with early type 2 diabetic nephropathy,which is associated with the increased SDF-1α levels.
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OBJECTIVE@#This study aims to compare the osteogenic differentiation capability of stem cells derived from human inflammatory periodontal ligament tissues (iPDLSCs) with those of stem cells derived from healthy periodontal ligament tissues (hPDLSCs). Both types of tissues were induced by stromal cell derived factor (SDF-1) in vitro.@*METHODS@#iPDLSCs and hPDLSCs were primarily cultured by tissue digestion method and purified by limited dilution cloning. The cells were passaged and identified by stem cell surface marker expression through flow cytometry. Then, we used thiazolyl blue tetrazolium bromide to detect and compare the proliferation capabilities of the iPDLSCs and hPDLSCs. Express of bone volumes were detected by alizarin red staining after SDF-1 was added to the cells. Using alkaline phosphatase, we evaluated the osteogenic differentiation capability of the cells induced by SDF-1. The expression levels of the osteogenesis-related genes of the cells induced by SDF-1 were determined by reverse transcription-polymerase chain reaction.@*RESULTS@#After purification, both iPDLSCs and hPDLSCs expressed stem cell markers. hPDLCSs had a higher proliferation capability than iPDLSCs. Osteogenesis-related genes had higher expression levels in the cells induced by SDF-1 than in those without induction (P<0.05). SDF-1 at 50 and 200 ng·mL⁻¹ concentration greatly affected the differen-tiation capabilities of iPDLSCs and hPDLSCs respectively.@*CONCLUSIONS@#iPDLSCs and hPDLSCs had osteogenic differentia-tion capability. The level of osteogenic differentiation in normal and inflamed periodontal ligament stem cells increases after SDF-1 induction.
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Humans , Cell Differentiation , Cell Proliferation , Cells, Cultured , Osteogenesis , Periodontal Ligament , Stem Cells , Stromal CellsABSTRACT
Objective To investigate the expression of miRNA-1 (miR-1) in colorectal cancer (CRC) tissues and its effect on proliferation and invasion of CRC cells in vitro as well as its mechanism. Methods A total of 180 CRC tissues from the hospitalized patients who underwent excision surgery and 114 adjacent cancer tissues in the Affiliated Cancer Hospital of Shanxi Medical University between June 2015 and December 2015 were collected. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-1 in 58 cases of CRC tissues and adjacent cancer tissues. Immunohistochemistry was used to detect the expression of stromal cell-derived factor-1 (SDF-1) protein in 122 CRC tissues and effect of overexpression or knockdown of miR-1 on the proliferation, colony formation and invasiveness of DLD1 cells, respectively. Western blot was used to determine the effect of overexpression or knockdown of miR-1 on the expression of SDF-1 in DLD1 cells. Results RT-qPCR results showed that the expression of miR-1 in CRC tissues was decreased compared with the corresponding adjacent cancer tissues (the relative expression level ratio < 0.5), and the low expression rate of miR-1 in CRC was 82.8％ (48/58). Immunohistochemistry results showed that the positive expression rate of SDF-1 in CRC tissues was higher than that in adjacent cancer tissues [81.1％ (99/122) vs. 8.9％ (5/56), χ2= 82.415, P< 0.01]. Cell function experiment showed that, compared with the control group, the proliferative activity of DLD1 cells that transfected miR-1 mimics was decreased, meanwhile, the colony formation, invasion and SDF-1 expression were reduced (P< 0.05). The proliferative activity, colony formation, invasion and SDF-1 expression in DLD1 cells that transfected miR-1 inhibitor were improved compared with those in the control group (P< 0.05). Conclusions The expression of miR-1 in CRC tissues is low and it may act as a tumor suppressor gene through affecting proliferation and invasive potential of CRC cells by regulating the expression of SDF-1.
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Objective: To observe the change of stromal cell-derived factor 1α/cysteine X cysteine receptor 4 (SDF-1α/CXCR4) signaling pathway during the process of axial stress stimulation promoting bone regeneration, and to further explore its mechanism. Methods: A total of 72 male New Zealand white rabbits were selected to prepare the single cortical bone defect in diameter of 8 mm at the proximal end of the right tibia that repaired with deproteinized cancellous bone. All models were randomly divided into 3 groups ( n=24). Group A was treated with intraperitoneally injection of PBS; Group B was treated with stress stimulation and intraperitoneally injection of PBS; Group C was treated with stress stimulation and intraperitoneally injection of AMD3100 solution. The X-ray films were taken and Lane-Sandhu scores of bone healing were scored at 2, 4, 8, and 12 weeks after operation, while specimens were harvested for HE staining, immunohistochemical staining of vascular endothelial growth factor (VEGF) and CXCR4, and Western blot (SDF-1α and CXCR4). The bone healing area was scanned by Micro-CT at 12 weeks after operation, and the volume and density of new bone were calculated. Results: X-ray film showed that the Lane-Sandhu scores of bone healing in group B were significantly higher than those in groups A and C at 4, 8, and 12 weeks after operation ( P<0.05). Micro-CT scan showed that the bone defect was repaired in group B and the pulp cavity was re-passed at 12 weeks after operation. The volume and density of new bone were higher in group B than in groups A and C ( P<0.05). HE staining showed that the new bone growth in bone defect area and the degradation of scaffolds were faster in group B than in groups A and C after 4 weeks. The immunohistochemical staining showed that the expressions of VEGF and CXCR4 in 3 groups reached the peak at 4 weeks, and group B was higher than groups A and C ( P<0.05). Western blot analysis showed that the expressions of SDF-1α and CXCR4 in group B were significantly higher than those in groups A and C at 4 and 8 weeks after operation ( P<0.05). Conclusion: Axial stress stimulation can promote the expression of SDF-1α in bone defect tissue, activate and regulate the CXCR4 signal collected by marrow mesenchymal stem cells, and accelerate bone regeneration in bone defect area.
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Objective: To evaluate the feasibility of immature permanent teeth pulp regeneration with a new method that utilizes the integration of concentrated growth factor (CGF) as a scaffold and stromal cell-derived factor-1 (SDF-1). Methods: Canine dental pulp cells (DPC) were isolated and cultured in vitro. Then the effects of SDF-1 and CGF were observed on DPC proliferation and differentiation. The pulpless model was established on the beagle’s immature incisors which were divided into four groups: natural pulp (A), empty cannel (B), CGF-filling (C) and SDF-1/CGF-filling (D). After 10 weeks, specimens were checked by imaging examination, RT-PCR and histological observation. Results: CGF extraction (CGFe) induced DPC proliferation while the combination of SDF-1 and CGFe enhanced this effect and also facilitated odontogenic and angiogenic differentiation of DPC. According to imaging examination, the apex growth of all four groups was in varying degrees. RT-PCR indicated the expressions of odontogenesis and angiogenesis related genes in group D were higher than those in group C. Besides, neonatal dentin and dental-pulp-like tissue were observed inside the canal of both group C and D, while only cementum-like tissue existed around root apex of group B. Conclusion:SDF-1 plays an important role in driving the process of pulp-like-tissue regeneration of immature permanent teeth by using CGF as an effective scaffold.
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@#AIM:To discuss the effect of retinal photocoagulation combined with conbercept on the aqueous humor vascular endothelial growth factor(VEGF)and stromal cell-derived factor-1(SDF-1)in patients with diabetic retinopathy(DR). <p>METHODS: Totally 120 patients with DR were selected from September 2016 to September 2018 in our hospital, according to the random number table, they were divided into combined group and photocoagulation group, 60 cases in each group. The photocoagulation group was treated with retinal photocoagulation, and the combined group was treated with retinal photocoagulation combined intravitreal injection of conbercept. The aqueous humor VEGF, SDF-1, CMT, BCVA and complication were compared between the two groups. <p>RESULTS: The postoperative aqueous humor(151.46±18.52,186.74±20.17pg/mL), SDF-1(466.72±50.21, 534.46±56.24mg/L)in the combined group and photocoagulation group were significantly lower than those in the preoperative, the combined group were lower than the photocoagulation group(<i>P</i><0.05). The 1 and 3mo postoperative CMT, BCVA in the combined group and photocoagulation group were significantly lower than those in the preoperative, the combined group were lower than the photocoagulation group(<i>P</i><0.05). There was no significant difference of the complication rate between combined group and photocoagulation group(6.7% <i>vs</i> 5.0%, <i>P</i>>0.05). <p>CONCLUSION: Retinal photocoagulation combined with conbercept can effectively reduce the aqueous humor VEGF and SDF-1 in patients with DR, which is conducive to improving the therapeutic effect of patients, and it is safety.