Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma / 中华内科杂志

Objective:To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods:This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUV max) of the focus on APA and NFA. The related factors of SUV max, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results:68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUV max differentiating APA and NFA was 0.932 ( P<0.001). When the SUV max cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUV max correlated positively with lesion size ( r=0.598) and aldosterone/renin activity ratio ( r=0.313) and correlated negatively with potassium level ( r=-0.286), renin activity ( r=-0.240) and age of diagnosis ( r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions:68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUV max of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke / 中国针灸

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.

Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （α4 β1）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy. MethodA total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl4， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg-1）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg-1， respectively） Bushen Jianpi Jiedu Liyan formula groups （n=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed increased red blood cell count in the urine at the 10th， 12th， 14th， 16th weeks （P<0.01）， and such increases were reduced in the drug intervention groups （P<0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （P<0.05）. Compared with those in the blank group， the protein levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （P<0.05）， and such un-regulations were inhibited in the drug intervention groups （P<0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （P<0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of α4 β1 and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （P<0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （P<0.05）. ConclusionBushen Jianpi Jiedu Liyan formula regulates the expression of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.

Effects of atractylodin on inflammatory damage of periodontal tissue and alveolar bone loss in periodontitis rats and its mechanism / 中国药房

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.

Biological Functions of CXCL12-CXCR4 in Human Malignant Tumors / 中国生物化学与分子生物学报

Metastasis and cell infiltration are the difficulties in the treatment of solid and lymphatic carcinoma and the main causes of disease recurrence and death. The migration of cancer cells is a prerequisite for tumor metastasis and invasion. The CXCL12-CXCR4 pathway plays an important role in the pathogenesis of solid tumors and leukemia. The interaction between CXCL12 and its receptor CXCR4 can activate multiple signaling pathways and regulate different physiological and pathophysiological processes. Thus, blocking CXCL12-CXCR4 binding and / or downstream pathways has clinical benefits in treating a variety of diseases and cancers. Although some CXCL12 and CXCR4 antagonists have been identified and have shown encouraging results in terms of antitumor activity, these drugs have not been widely used in clinical patients due to their serious toxic and side effects. There is an urgent need to develop novel CXCL12-CXCR4 axis antagonists for the treatment of tumors. Herein, we review the recent research progress of CXCR4 pathway in solid tumors and leukemia, and discuss the therapeutic value and future research direction of CXCR4 pathways in solid tumors and leukemia.

Effect and Mechanism of Cxcr4 Gene-Modified BMSC-Derived Exosomes on Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To explore the improvement effect of CXC chemokine receptor 4 (Cxcr4) gene-modified bone marrow mesenchymal stem cell (BMSC)-derived exosomes on aplastic anemia (AA), and make a preliminary exploration of the mechanism.@*METHODS@#Mouse BMSCs were isolated and cultured, then infected by recombinant lentivirus carrying Cxcr4 gene. The expression of green fluorescence was observed through fluorescence microscope, the expression of Cxcr4 mRNA was detected by real-time fluorescence quantitative PCR, and the BMSC-derived exosomes modified with Cxcr4 gene were extracted. Mouse models of AA were constructed, and control group, model group (AA), AA+BMSC group, AA+NC-BMSC group, AA+Cxcr4-BMSC group were set up. Except control group and model group, the other three groups of mice were injected 400 μl exosomes from different sources via the tail vein, after 2 weeks, the routine blood indices and the number of bone marrow nucleated cells were detected, the pathological changes of bone marrow were observed by HE staining, and the expression level of Treg cells was detected by flow cytometry.@*RESULTS@#Mouse BMSCs were successfully isolated, and BMSCs with high expression of Cxcr4 and their exosomes were obtained. Compared with the control group, the number of red blood cell (RBC), white blood cell (WBC), and platelet (PLT), the hemoglobin (Hb) content and proportion of Treg cells in the peripheral blood of mice in the model group significantly decreased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). The proliferation level of nucleated cells was low, and the medullary cavity was filled with a large number of fat cells. Compared with the model group, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+BMSC group, AA+NC-BMSC group, and AA+Cxcr4-BMSC group significantly increased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01), and pathological changes of bone marrow were improved. In addition, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+Cxcr4-BMSC group were significantly higher than those in the AA+BMSC group (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01).@*CONCLUSION@#Injection of Cxcr4 gene-modified BMSC-derived exosomes has a certain improvement effect on AA mice, and the mechanism may be related to an increase of the proportion of Treg cells.

Effect of Astragali Radix-Curcumae Rhizoma on SDF-1/CXCR4/NF-κB Signaling Pathway of Orthotopic Transplantation Model of Colon Cancer in Mice / 中国实验方剂学杂志

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^-1） group，and low- （0.32 g·kg^-1）， medium- （0.64 g·kg^-1）， and high-dose （1.28 g·kg^-1） 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 D₁， 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 D₁， 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.

Cross-talk between CXC chemokine ligand 10-CXC chemokine receptor 3 axis and CC chemokine ligand 17-CC chemokine receptor 4 axis in the pathogenesis of oral lichen planus / 华西口腔医学杂志

OBJECTIVES@#This study aimed to determine whether a correlation existed between CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) and CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) in the pathogenesis of oral lichen planus (OLP).@*METHODS@#Peripheral blood of OLP patients (non-erosive and erosive groups) and healthy controls were collected, and T cells were isolated and purified. T cells were co-cultured with three groups: blank, anti-CXCR3, and anti-CCR4. CXCR3 and CCR4 expression were detected by flow cytometry, and CXCL10 and CCL17 were detected by enzyme-linked immunosorbent assay, respectively.@*RESULTS@#The purities of T cells were all >95% in the three groups (@*CONCLUSIONS@#Two axes interact with each other in the pathogenesis of OLP and may play different roles in its occurrence and development.

LncRNA Xist Promotes Proliferation and Migration of Rat BMSC by Regulating CXCR4 Expression / 中山大学学报(医学科学版)

@#【Objective】To explore the role of lncRNA Xist in proliferation and migration of rat bone marrow mesenchymal stem cells（BMSC）and its possible mechanism.【Methods】BMSC were isolated，cultured and identified from the femur and tibia of 3 weeks old SD female rats in vitro. SiRNAs was designed and screened to acquire a high silencing efficiency siRNA. Lipo2000 was used to transfected si- Xist and si- NC into BMSC of the experimental group（si- Xist group）and the control group（si-NC group）. BMSC proliferation capacity was determined by CCK-8 assay. The transverse and longitudinal mobility of BMSC were measured by wound healing assay and transwell migration assays. QPCR was performed to verify the silencing efficiency of lncRNA Xist and detect the expression levels of SDF- 1 and CXCR4 mRNA. Western blot was used to quantify the expression of CXCR4 protein.【Results】The P3 generation BMSC shows shuttle- like or whirlpool-like，and flow cytometry showed CD11b（-），CD34（-），CD45（-），CD44（+），CD90（+），CD105（+）. When siRNAs were used to interfere with the expression of lncRNA Xist in BMSC ，the silencing efficiency of three siRNAs was 67.92% ，68.72% and 98.32% ，respectively. CCK- 8 assay showed that the OD450 value of si- Xist group decreased compared with si-NC group at 24 h and 48 h（P < 0.001，P < 0.01，respectively）and had no statistical difference at 12 h（P > 0.05）. Wound healing assay showed that the wound healing percentage of si-Xist group was lower than that of si-NC group（P < 0.05）；and the transwell migration assay showed that，compared with si- NC group，the cells that migrated through the polycarbonate membrane were obviously decreased at 6 h（P < 0.001）. QPCR experiment showed that CXCR4 expression in si-Xist group was lower than that in si-NC group at mRNA level（P < 0.05），while SDF-1 expression showed no significant statistical difference（P > 0.05）. Western blotting confirmed that CXCR4 expression in si- Xist group was lower than that in si-NC group（P < 0.05）.【Conclusions】LncRNA Xist promotes proliferation and migration of rat BMSC by regulating CXCR4 expression.

Effect of Ru′ai Shuhou Prescription on Proliferation and Metastasis of Breast Cancer MDA-MB-453 Cells Through SDF-1/CXCR4 Biological Axis / 中国实验方剂学杂志

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.

SDF-1α/CXCR7 mediating colon carcinoma cells resistant to 5-FU / 肿瘤

Objective: To investigate the effects of stromal cell-derived factor-1α (SDF-1α)through CXC-domain chemokine receptor 4 (CXCR4) and CXCR7 on colonic cancer cells resistant to 5-fluorouracil (5-FU), and to explore its possible mechanism. Methods: The expression levels of CXCR4 and CXCR7 in colonic cancer SW480, SW620, HCT116 and HT29 cells were detected by Western blotting. After treatment with SDF-1α, SDF-1α in combination with AMD3100 (CXCR4 inhibitor) or SDF-1α in combination with anti-CXCR7 monoclonal antibody for 6 hours, the SW480 and HT29 cells were then treated with 3.1, 6.25, 12.5, 25, 50, 100 and 150 μg/mL 5-FU for 48 hours. The half inhibitory concentration (IC50) value of 5-FU was detected by sulforhodamine B (SRB) assay. The expressions of drug-resistant proteins P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) were detected by Western blotting. Results: The expression levels of CXCR4 and CXCR7 in SW480 and HT29 cells were higher than those in SW620 and HCT116 cells (all P 0.05). The expression levels of P-gp in SW480 and HT29 cells in group of SDF-1α in combination with anti-CXCR7 monoclonal antibody were lower than those in SDF-1α group (both P 0.05). The expression level of MRP-1 had no significant difference among different groups (P > 0.05). Conclusion: SDF-1α can promote the resistance to 5-FU in colonic cancer cells. This effect may be related to up-regulating the expression level of P-gp through SDF-1α/CXCR7 signal pathway.

Expression of chemokine receptor and vascular endothelial growth factor in ovarian cancer / 国际检验医学杂志

Objective To explore the correlation between chemokine receptor 4(CXCR4) and vascular en-dothelial growth factor (VEGF) and ovarian cancer.Methods 59 cases of oophorectomy were selected from February 2014 to April 2015.According to the pathological results,the patients were divided into ovarian canc-er group(group A) with 32 cases and benign tumor group (group B) with 27 cases.Another 35 patients un-dergoing non ovarian surgery were selected as control group (group C).The expressions of CXCR4 and VEGF in ovarian tissues of each group were detected,and the correlation with ovarian cancer was analyzed.Results The expression levels of CXCR4 and VEGF in the three groups were in the turn of A,B and C,and the differ-ence was statistically significant (P<0.05).The positive rate of VEGF was higher in low differentiation canc-er tissues,and the difference was statistically significant (P<0.05);the positive rate of VEGF was relatively high in the cancer tissues of clinical stage Ⅲ and IV,and the difference was statistically significant (P< 0. 05);the positive rates of CXCR4 and VEGF were higher in ovarian cancer with peritoneal metastasis or lymph node metastasis,and the difference was statistically significant (P<0.05).The expression of CXCR4 in ovarian canc-er tissues was positively correlated with the expression of VEGF (P<0.05).Conclusion CXCR4 and VEGF were highly expressed in ovarian cancer tissues,and the two involved in the development,invasion and metastasis of tumors.

Berberine-Promoted CXCR4 Expression Accelerates Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Persons with Prehypertension / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate whether the berberine treatment can improve endothelial repair capacity of early endothelial progenitor cells (EPCs) from prehypertensive subjects through increasing CXC chemokine receptor 4 (CXCR4) signaling.</p><p><b>METHODS</b>EPCs were isolated from prehypertensive and healthy subjects and cultured. In vivo reendothelialization capacity of EPCs from prehypertensive patients with or without in vitro berberine treatment was examined in a nude mouse model of carotid artery injury. The protein expressions of CXCR4/Janus kinase-2 (JAK-2) signaling of in vitro EPCs were detected by Western blot analysis.</p><p><b>RESULTS</b>CXCR4 signaling and alteration in migration and adhesion functions of EPCs were evaluated. Basal CXCR4 expression was significantly reduced in EPCs from prehypertensive patients compared with normal subjects (P<0.01). Also, the phosphorylation of JAK-2 of EPCs, a CXCR4 downstream signaling, was significantly decreased (P<0.01). Berberine promoted CXCR4/JAK-2 signaling expression of in vitro EPCs (P<0.01). Transplantation of EPCs pretreated with berberine markedly accelerated in vivo reendothelialization (P<0.01). The increased in vitro function and in vivo reendothelialization capacity of EPCs were inhibited by CXCR4 neutralizing antibody or pretreatment with JAK-2 inhibitor AG490, respectively (P<0.01).</p><p><b>CONCLUSION</b>Berberinemodified EPCs via up-regulation of CXCR4 signaling contributes to enhanced endothelial repair capacity in prehypertension, indicating that berberine may be used as a novel potential primary prevention means against prehypertension-related atherosclerotic cardiovascular disease.</p>

Effect of atorvastatin on expression of peripheral blood EPC surface mar-kers in patients with acute ST-segment elevation myocardial infarction / 中国病理生理杂志

AIM:To compare the effects of atorvastatin at different doses on the function of endothelial proge-nitor cells (EPCs) in the patients with ST-segment elevation myocardial infarction (STEMI).METHODS:The patients of STEMI (n=40) were chosen.According to treatment with different doses of atorvastatin calcium tablet, they were randomly divided into a group of 20 mg and a group of 40 mg (20 cases in each group).The EPCs isolated from the patients were identified and quantitatively analyzed at different time points (before the treatment and on days 5, 10, 15, 20, 30, 60, 90 and 120 after the treatment) by flow cytometry.The surface markers of the EPCs, CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and silent information regulator 1 (SIRT1), were also detected.RESULTS:On the 5th day, the group of 40 mg demonstrated stronger cell proliferation capability and higher expression levels of CXCR4, VEGF and bFGF than the group of 20 mg (P<0.05).From the 10th day to 120th day, the group of 20 mg revealed stronger cell proliferation capability and higher expression levels of CXCR4, VEGF and bFGF than the group of 40 mg (P<0.05).Within 30 d, the expression of SIRT1 showed no significant diffe-rence between the 2 groups, yet it witnessed a marked change after that and peaked on the 60th day with a drop afterwards.At each time point, the SIRT1 expression level in the group 20 mg was observed higher than that in the group of 40 mg (P<0.05).CONCLUSION:In the acute phase, the repair function of the body treated with atorvastatin at dose of 40 mg is better than that with 20 mg.However, in a long term the low concentration of statin therapy works better in improving the vascular intima and promoting the angiogenesis than high concentration.

Promotion of autophagy and the secretion of CXCR4 of human umbilical cord mesenchymal stem cells induced by low-dose immunosuppressive durgs / 中华器官移植杂志

Objective To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on autophagy and the secretion of chemokine receptor CXCR4 induced by low-dose immunosuppressive durgs.Methods Flow cytometry was used to detect the changes of hUC-MSCs surface markers after treatment with low-dose tacrolimus and rapamycin.The effect of treatment with tacrolimus and rapamycin on proliferation of hUC-MSCs was analyzed with WST-1 assay.Regular RT-PCR was applied to analyze the mRNAs expression of ligands such as LC3B,Atg5 and Beclin1 in hUC-MSCs.Western blotting was carried out to detect the expression of LC3B,Atg5,Beclin1 and p-ULK1 in hUC-MSCs after treatment with tacrolimus and rapamycin.The secretion of chemokine receptor CXCR4 in hUC-MSCs was analyzed under the state of autophay by flow cytometry.Results Flow cytometry analysis confirmed low-dose immunosuppressive drugs tacrolimus and rapamycin did not cause changes in hUC-MSCs phenotypes significantly.Low-dose tacrolimus had no cytotoxic effect on hUC-MSCs,while,rapamycin could inhibit the proliferation of hUC-MSCs after 24 h or 48 h,with survival rate being 73.66％ and 68.81％ (P＜0.05) of controls,respectively.Moreover,both tacrolimus and rapamycin could inhibit PI3K/AKt/mTOR signaling pathway to activate hUC-MSCs autophagy,and the related proteins of LC3B,Atg5 and Beclin1 increased significantly and induced the up-regulation of CXCR4 secretion.Conclusion Our results here demonstrated that low-dose tacrolimus and rapamycin induce autophagy in hUC-MSCs and promote the secretion of CXCR4.

Expression of CXC chemokine receptor 4 in clear cell renal cell carcinoma / 中华泌尿外科杂志

Objective To investigate the expression of CXC chemokine receptor 4 (CXCR4) in clear cell renal cell carcinoma (ccRCC) and its relationship with the clinical pathological parameters of ccRCC.Methods The expression of CXCR4 was detected by immuno-histochemistry method in 63 cases of ccRCCs,20 cases of para-carcinoma tissues and 20 cases of normal renal tissues.The correlation between expression level of CXCR4 and clinical pathological parameters of ccRCC patients were analyzed,and the clinical significance of its expression in ccRCC was evaluated.Results The positive expression rate of CXCR4(49.2％) in ccRCCs was significantly higher than that in para-carcinoma tissues (15％) and normal renal tissue (10％),and the difference was statistically significant (P ＜ 0.05).The expression level of CXCR4 and the clinical stage and pathological grade of ccRCC were correlated (P ＜ 0.05),and was associated with lymph node transfer (P ＜ 0.05).The CXCR4 negative group overall survival rate [55.2％ (16/29)] and the average survival time(46 months) was significantly better than the positive group [38.5％ (10/26),32 months;P ＜ 0.05].Conclusions The expression level of CXCR4 in ccRCC is correlated with the clinicopathological parameters and prognosis.CXCR4 is expected to be an important marker for diagnosis and prognosis evaluation of renal cell carcinoma.

BYHWD promotes endothelial progenitor cells to repair damaged vascu-lar endothelium / 中国病理生理杂志

AIM:To investigate the role of Buyanghuanwu decoction(BYHWD) in promoting endothelial pro-genitor cells(EPCs)-induced recovery of damaged vascular endothelium. METHODS:The endothelial damaged rats were lavaged with BYHWD and injected with EPCs through vena caudalis. The repaired situation of damaged endothelium was observed. RESULTS:Compared with EPCs group and BYHWD group,the endothelial thickness was reduced, the levels of calcium,triglycerides and total cholesterol were decreased,but the high density lipoprotein levels were increased. In ad-dition,the protein expression of vascular endothelial nitric oxide synthase and vascular stromal cell-drived factor-1 was sig-nificantly increased,but the expression of CXC chemokine receptor-4 was significantly reduced in BYHWD+EPC group. CONCLUSION:BYHWD promotes EPCs repairing damaged endothelium,the mechanism may be related to improve the internal environment and promotes the EPCs homing.

Effects of SDF-1 and its receptor CXCR4 on colorectal cancer liver metastasis potential / 中国现代普通外科进展

Objective:To investigate chemokine stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 in colon cancer liver metastasis potential effect.Methods:Selected colorectal cancer cell line HT-29,were divided into SDF-1 group(SDF-110 μg/L),SDF-1 +CXCR4 Monoclonal antibody group (10 μg/L SDF-1+20 μg/mL CXCR4) and control group (culture medium),detected SDF-1 and anti CXCR4 monoclonal antibody on HT-29 cell proliferation and migration ability,established nude mouse model of colorectal cancer liver metastasis,detected AMD3100 on nude mice liver metastasis tumor number effect.Results:SDF-1 group in 570nm A value was 0.82 + 0.09,was significantly higher than that of SDF-1+CXCR4 monoclonal antibody group and the control group 0.56 ± 0.10 and 0.53 ± 0.04,the difference was statistically significant (P＜0.05);SDF-1 group of HT-29 cells throughpolycarbonate microporous membrane the number was 156.37 ± 2.11,was significantly higher than that of SDF-1 +CXCR4 monoclonal antibody group and the control group 101.20 ± 28.40 and 97.19 ± 35.39,the difference was statistically significant (P＜0.05);AMD3100 group nude mice liver metastasis tumor number was 6.38 ± 2.11,was significantly lower than that in phosphate buffer solution(PBS) group 18.39 ± 7.59,the difference was statistically significant(P＜0.05).Conclusion:SDF-1and its receptor CXCR4 may be involved in the process of liver metastasis of colon cancer,and its possible mechanism as SDF-1 induced cell proliferation and directional migration.

Intervention of AMD3100 in lung tissues of rats during pulmonary oxygen intoxication / 军事医学

Objective To investigate the intervention of chemokine receptor 4(CXCR4) antagonist AMD3100 in lung tissues of rats during pulmonary oxygen intoxication.Methods Forty SD rats were randomly divided into 4 groups:normal pressure air PBS group, normal pressure air antagonist group , oxygen exposure PBS group and oxygen exposure antagonist group, each consisting of 10 animals.The last two groups were compressed to 0.23 MPa at an exponential rate of 0.1 MPa/min by pure oxygen.Pathological changes of lung tissues were observed by hematoxylin eosin stain.Changes in TNF-αand IL-1βexpression levels in the lung tissues of rats were detected by ELISA.Changes in CXCR4 expression levels were ob-served by Western blotting.Results Pathological examination indicated that edema and hemorrhage in the alveolar and pulmonary interstitial tissue of oxygen exposure antagonist group were lighter than in oxygen exposure PBS group.The levels of TNF-α, IL-1βand cleaved-caspase-3 in the lung tissues of the oxygen exposure antagonist group were lower than in oxy-gen exposure PBS group.Conclusion Blocking CXCR4 with AMD3100 can effectively alleviate lung injury during pulmo-nary oxygen intoxication.

Effects of mesenchymal stem cells surface CXC chemokine receptor 4 over-expression on repair of ischemia reperfusion injured kidney / 中华急诊医学杂志

Objective To observe the effects of mesenchymal stem cells (MSCs) surface CXC chemokine receptor 4 over-expression on the repair of kidney after ischemia reperfusion (I/R) injury.Methods The MSCs were co-cultured with I/R injured renal cell homogenate supernatant.The MSCs surface CXCR4 and stromal cells derived factor-1 (SDF-1α) protein levels were detected by Western blot, chemotactic ability of MSCs to SDF-1 was investigated by transwell test.The I/R injured renal model was made and pathological changes were observed in control group, I/R group, MSCs injection group and CXCR4 neutralize antibody group.Renal CXCR4 protein expression was measured by immunofluorescence histochemistry, SDF-1α、 CXCR4、 hepatocyte growth factor (HGF) and epidermal growth factor (EGF) mRNA were detected by Real-time quantitative polymerase chain reaction (RT-PCR).Comparisons among multiple groups were performed using One-way analysis of variance, and comparisons between groups were carried out using independent-sample t-test.Results In vitro, the SDF-1α protein expression markedly increased in I/R injured renal tissue homogenate, but the difference was not significant between I/R group and CXCR4 antibody group (t =0.862, P =0.403).MSCs surface CXCR4 protein expression increased significantly after co-cultured with I/R injured renal tissue homogenate (F =95.957, t =10.166, P ＜ 0.01), and the chemotactic ability of MSCs to SDF-1 increased at the same time (F =82.459, t =6.826, P ＜ 0.01), the CXCR4 protein expression (t =13.657, P ＜ 0.01) and the chemotactic ability (t =12.662, P ＜0.01) could be decreased by CXCR4 neutralize antibody.In vivo, renal tubular structure was destroyed in I/R group.After MSCs injection, the renal pathological injury improved rapidly, but the improvement could be inhibited by CXCR4 antibody.The expression of SDF-1α mRNA and level of SDF-1a protein increased in I/R group, but there was no significant difference among different groups (F =1.909,P =0.173).MSCs injection markedly up-regulated the CXCR4 protein and mRNA expression (F =6.663, P =0.006).Following the increase in CXCR4 expression, the expressions of HGF mRNA (F =11.898,P ＜ 0.01) and EGF mRNA (F =5.309, P ＜ 0.05) increased gradually which could be restrained by CXCR4 antibody (t =5.312, t =4.310, P ＜ 0.01).Conclusions I/R injured renal microenvironment markedly increased the mesenchymal stem cells surface CXCR4 expression, and increased CXCR4 expression can induce MSCs chemotaxis and stimulate the secretion of renal protective growth factors paracrine promoting the repair of the kidney.