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.

The Effects and Regulatory Mechanism of Targeting CXC Chemokine Receptor 1/2 Combined with Ara-C on the Malignant Biological Behaviors of U937 Cells of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML.@*METHODS@#Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR).@*RESULTS@#Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05).@*CONCLUSION@#Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.

Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

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.

Epidemiological analysis on the susceptibility of CXCR3 gene polymorphism to COPD in the elderly population in Liangjiang New Area of Chongqing / 公共卫生与预防医学

Objective To explore and analyze the epidemiology of susceptibility to chronic obstructive pulmonary disease (COPD) among the elderly population in Liangjiang New Area of Chongqing based on CXC chemokine receptor 3 (CXCR3) gene polymorphism. Methods From January 2020 to September 2022, the Medical Laboratory Department of Chongqing Liangjiang New Area People's Hospital selected COPD patients and received treatment. Among the 276 patients who met the criteria were included in the study and included in the observation group. Among the 512 patients with healthy pulmonary function in the same period were included in the control group. The data of the two groups of patients were analyzed, and the genotypes were detected by SBaPhotoshot technology to analyze the relationship between gene polymorphism and the susceptibility and clinical characteristics of COPD. Results There was no significant difference between the two groups in age, sex, BMI and blood eosinophil granulocyte levels, which was comparable (P>0.05). There were significant differences in smoking history, pulmonary function index , MMP-9 and TIMP-1 levels (P0.05). In the observation group, the MMP-9 level of rs2280964 locus was significantly different (P=0.003), while the TIMP-1 level was not significantly different (P=0.187); There was no significant difference in MMP-9 and TIMP-1 levels among the three genes at rs34334103 locus (all P>0.05). The level of MMP-9 in homozygous TT patients with rs2280964 locus was significantly higher than that in homozygous CC patients (P=0.024). There were differences in FEV1/FVC of patients with CXCR3 rs34,334,103 gene distribution (P=0.008), among which there were significant differences in CC+CT and TT recessive models (P0.05). Conclusion CXCR3 gene polymorphism is significantly associated with the susceptibility to COPD, and also with the serum levels of MMP-9 and FEV1/FVC, which can be used as a new target for clinical research and treatment.

Effect of CXC chemokine receptor 7 on cell cycle of neuronal cells in ischemic stroke / 中华危重病急救医学

Objective:To investigate the function and mechanism of CXC chemokine receptor 7 (CXCR7) in neuronal cells of ischemic stroke.Methods:The expression of CXCR7 in human neuroblastoma SH-SY5Y cells was interfered by small interfering RNA (si-RNA) technique. Oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was constructed in SH-SY5Y cells. CXCR7 protein expression and cell cycle were detected by flow cytometry (FCM). The protein expression of CXCR7 and Akt signaling pathway was detected by Western blotting.Results:After 6 hours of OGD/R, the expression of CXCR7 was significantly decreased compared with OGD/R 0 hour (CXCR7/GAPDH: 0.483±0.098 vs. 1.000±0.000 by Western blotting and 0.686±0.0524 vs. 1.000±0.000 by FCM, both P < 0.01), cell cycle arrest in G0/G1 phase (1.190±0.040 vs. 1.000±0.000, P < 0.01). After CXCR7 si-RNA interference with SH-SY5Y cells, OGD/R was constructed again for 6 hours. Compared with negative control group (si-NC group) under the same environment, the expression of CXCR7 and phosphorylated Akt (p-Akt) was significantly decreased (CXCR7/GAPDH: 0.471±0.051 vs. 1.000±0.000, p-Akt/GAPDH: 0.616±0.027 vs. 1.000±0.000, both P < 0.001) and cell cycle arrest in G0/G1 phase (1.105±0.033 vs. 1.000±0.000, P < 0.05). Conclusion:The CXCR7 could regulate the cycle of neuronal cells in ischemic stroke through Akt signaling pathway, which has a protective effect on neuronal cells.

Youguiwan Regulates CXCL8/CXCR1/2 Signaling Pathway and Ang-1 and Ang-2 Expression to Promote Ovarian Angiogenesis in Rats / 中国实验方剂学杂志

ObjectiveTo study the effects of Chinese herbal compound Youguiwan on angiogenesis of rats with ovarian dysfunction caused by natural aging and its relationship with chemokine interleukin 8 （CXCL8）/CXC chemokine receptor 1/2 （CXCR1/2） signaling pathway， angiopoietin 1 （Ang-1）， and angiopoietin 2 （Ang-2）， so as to explore its mechanism in improving the ovarian function. MethodFifty six female SD rats were randomly divided into the young control group （n=8） and modeling group （n=48， ovarian dysfunction caused by natural aging）. Rats in both the young control and modeling groups were routinely fed， during which the ones in the modeling group underwent exfoliative cytology of vaginal smears for five to seven days. The ones presented with prolonged estrous cycle， followed by continuous estrus and repeated pseudopregnancy revealed by vaginal cytology during four consecutive estrous cycles indicated early aging， and the young rats with keratinocyte proliferation index higher than 50% for 10 consecutive days were classified into the young control group. The successfully modeled rats were randomly divided into the early-aged group， estrogen （65 μg·kg-1·d-1） group， Zuoguiwan （33 g·kg-1·d-1） group， as well as the low-， medium-， and high-dose （1.2， 2.4， 4.8 g·kg-1·d-1） Youguiwan groups. Rats in the young control group and the early-aged group were gavaged with the same volume of normal saline for 30 days. After the experiment， the morphological changes in rat ovary were observed by hematoxylin-eosin （HE） staining. The protein expression levels of chemokines CXCL8， CXCR1， CXCR2， Ang-1， and Ang-2 in rat ovary were detected by Western blotting and immunohistochemistry， and the mRNA expression levels of CXCL8， CXCR1， CXCR2， Ang-1， and Ang-2 by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the young control group， the early-aged group exhibited reduced number of growing follicles， corpus luteum， and blood vessels at all levels， elevated atretic follicles （P<0.01）， up-regulated protein and mRNA expression of CXCL8， CXCR1， and CXCR2 in the ovarian tissue （P<0.01）， and down-regulated Ang-1 and Ang-2 protein and mRNA expression （P<0.05）. Compared with the early-aged group， each medication remarkably increased the number of growing follicles， corpus luteum， and blood vessels （P<0.05）， lowered the number of atretic follicles （P<0.05）， down-regulated the protein and mRNA expression levels of CXCL8， CXCR1， and CXCR2 in the ovarian tissue （P<0.05）， and up-regulated the protein and mRNA expression levels of Ang-1 and Ang-2 （P<0.05）. ConclusionYouguiwan down-regulates the levels of CXCL8， CXCR1， and CXCR2 in rat ovary and up-regulates the levels of Ang-1 and Ang-2 to promote ovarian angiogenesis and improve rat ovarian function.

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.

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.

Effects of CXC-chemokine Receptor 7 Expression in Endothelial Progenitor Cells on Angiogenesis after Cerebral Ischemia-reperfusion Injury / 中国康复理论与实践

Objective:To explore the effect of upregulating CXC-chemokine receptor 7 (CXCR7) in endothelial progenitor cells (EPCs) on angiogenesis after cerebral ischemia-reperfusion injury. Methods:EPCs were isolated and cultured from human umbilical cord blood and identified. Then, the EPCs were transfected with CXCR7 overexpression lentiviral vector, and the expression of CXCR7 was identified with real-time PCR and Western blotting. The tube-like structure formation and apoptosis of EPCs under oxidized low density lipoprotein (ox-LDL) were detected with tube-like structure formation test and Annexin V/PI staining. Cerebral ischemia-reperfusion injury model in rats was established, and the qualified model rats were randomly divided into three groups after 24 hours reperfusion: PBS group (n = 12) was injected with phosphate buffers through tail vein, control group (n = 12) was injected the EPCs infected with control lentiviral vector, and CXCR7 group (n = 12) was injected with EPCs infected with CXCR7 overexpression lentiviral vector. Neurological function scores were determined seven and 14 days after transplantation. The cerebral infarct volume was measured, the number of GFP-positive cells in the ischemic site and the density of capillary were observed. Results:The expression of CXCR7 in EPCs increased after transfection (P < 0.01). Overexpression of CXCR7 improved tube formation and reduced apoptosis of EPCs under ox-LDL (P < 0.05). Compared with PBS and control groups , neurological function improved in CXCR7 group, with less infarct volume, more GFP-positive cells and density of capillary (P < 0.05). Conclusion:Up-regulating CXCR7 can improve the survival and angiogenesis of EPCs, and improve the repair of cerebral ischemia-reperfusion injury.

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>

Stromal cell-derived factor-1 inducing metastasis squamous cell carcinoma of head and neck induced via integrin ανβ3-CXC chemokine receptor 4/7 biological axis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To observe the influence of LM609/AMD3100/CCX754 on chemotactic capability, cytoskeleton, and expression of integrin ανβ3 protein of squamous cell carcinoma of head and neck (SCCHN) cell line PCI-13 induced by stromal cell-derived factor-1 (SDF-1) in vitro.</p><p><b>METHODS</b>Migration assays, flow cytometry and immunofluorescence were used to observe the effects of SDF-1, LM609, AMD3100 and CCX754 on the migration, cytoskeleton and the expression of integrin ανβ3 protein in PCI-13 cell lines.</p><p><b>RESULTS</b>SDF-1 favored PCI-13 cell migration, pseudopod formation, and activities of integrin ανβ3 phosphorylation. LM609, AMD3100, and CCX754 blocked all these effects.</p><p><b>CONCLUSIONS</b>SDF-1 can induce metastatic SCCHN by integrin ανβ3-CXC chemokine receptor (CXCR) 4/CXCR7 axi. LM609, AMD3100, and CCX754 and can reduce the regulation of SDF-1 on SCCHN activity.</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.

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 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.

Expression of CXC chemokine receptor 7 in atherosclerotic ApoE-defi-cient mice and therapeutic impact by atorvastatin / 中国病理生理杂志

AIM:To evaluate the expression level of CXC chemokine receptor 7 (CXCR7) in atherosclerotic apolipoprotein E-deficient ( ApoE-/-) mice induced by high-fat diet ( HFD) and the effects of atorvastatin on it .METH-ODS:ApoE-/-male mice (8-week-old) were used and were randomly divided into 3 groups following 1-week normal ro-dent diet:normal diet control (NDC) group , HFD group and HFD+statins (HFD+Sat) group.HE staining and oil red O staining were used to observe the atherosclerotic lesion burdens in the aortas .The expression of CXCR7 on the aortas was detected by Western blot and immunohistochemistry .The expression of Akt and endothelial nitric oxide synthase ( eNOS) in the aorta was determined by Western blot .RESULTS: Few lesions were found in the aortas in NDC group .Apparent atherosclerotic plaque burdens were seen in HFD group and HFD +Sat group, while the atherosclerotic plaque burdens in HFD+Sat group were notably reduced compared with HFD group .The protein levels of CXCR7, eNOS and Akt in aorta in HFD group and HFD+Sat group were significantly decreased compared with NDC group , while those in HFD+Sat group were increased compared with HFD group .The protein level of p-eNOS in the aorta and the concentration of NO in the plas-ma in HFD group were decreased compared with NDC group and HFD +Sat group.CONCLUSION: In ApoE-/-mice, HFD increases the lipid level and promotes the development of atherosclerosis by downregulating the expression of CXCR 7, Akt and eNOS.Atorvastatin reverses the above effect of hypercholesterolemia on the expression of CXCR 7, Akt and eNOS, thus playing the role in treating atherosclerosis .

Expressions of IL-16, IFN-γ and CXCR3 in plasma of patients with chronic obstructive pulmonary disease and their clinical significance / 实用医学杂志

Objective Toexplore the expressions of interleukin-16 (IL-16), interferon-γ (IFN-γ), CXC chemokine receptor 3 (CXCR3), and CRP and their clinical significance in acute exacerbation chronic obstructive pulmonary disease by observing the changes in these factors in patients with AECOPD. Methods 103 patients with AECOPD and 20 healthy controls were collected. According to the 2013 GOLD guideline, all the patients with AECOPD were divided into4 groups(group A of 21 patients, B of 30, C of 27, andD of 25). Results As compared withthe control group, plasma concentrations of IL-16, IFN-γ, CXCR3. and CRP were significantly increased in the patients with AECOPD (P < 0.01), and as the severity of the disease was elevating, these expression levels were significantly increased.While the expression levels of IL-16, IFN-γ, CXCR3, and CRP levels were significantly reduced after treatment, but they were still higherthan those in the control group (P < 0.05). The expression levels of serum IL-16, IFN-γ, CXCR3, and CRP were significantly correlated in patients with AECOPD. Conclusions Expressions of IL-16, IFN-γ and CXCR3 are significantly increased in AECOPD, which is correlated with disease severity and decreased after treatment, suggesting that these three factors may be associated with the occurrence and development of COPD.

Serum levels of CXC chemokine ligand 10 and chemokine receptors in patients with type 1 diabetes mellitus / 中华内分泌代谢杂志

Serum levels of CXC chemokine ligand 10 (CXCL10) and chemokine receptor 3 (CXCR3) were determined in 50 patients with type 1 diabetes mellitus (T1 DM) and 30 normal control subjects by ELISA method.The results showed that serum levels of CXCL10 and CXCR3 in T1DM patients were significantly higher than those in normal subjects [(258.17 ± 39.12 vs 96.47 ± 26.91) ng/L,(851.87 ± 70.04 vs 441.82 ± 72.24) pg/ml,both P＜0.05].Serum level of CXCL10 in patients dropped sequentially with durations of diabetes ＜6 weeks,≥6 weeks or ＜3 years,and ≥ 3 years,being statistically significant between groups (P＜0.05).These results suggest that serum levels of CXC10 and CXCR3 may reflect the immune activity in T1DM.

Expression of CXC chemokine receptor 4 in Barrett esophagus, esophageal adenocarcinoma and esophageal squamous cell carcinoma and its clinical significance / 中华消化内镜杂志

Objective To investigate the expressions of CXCR4 in Barrett esophagus (BE), esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC), and its relationship with pathology, clinical staging and lymph node metastasis. Methods The expressions of CXCR4 in 56 cases of normal esophageal mucosa, 80 BE (including 22 BE with multifocal dysplasia), 25 EADC and 48 ESCC were examined with immunohistochemical method. Results CXCR4 was expressed in most samples of BE (80. 8% ), EADC (68. 0% ) and ESCC (78.4%) without significant difference ( P ＞ 0. 05 ), which was significantly higher than that in normal esophageal mucosa (39. 3%, P ＜0. 01 ). The level of CXCR4 expression in BE, EADC or ESCC were not related with gender, age, or location of the foci ( P ＞ 0. 05). There was no significant difference in CXCR4 expression between BE without dysplasia or BE with multifocal dysplasia ( P ＞ 0. 05 ). CXCR4 expression level in well-differentiated EADC was significantly higher than that of mild or poorly differentiated (P ＜ 0. 05 ). CXCR4 expression level was higher in EADC with lymph node metastasis than those without ( P ＜ 0. 05 ). CXCR4 level in ESCC with TNM staging grades Ⅲ -Ⅳ was higher than that of grades Ⅰ - Ⅱ, and this variable was also higher in cases with lymph node metastasis than those without (P ＜ 0. 05), so was the case of well and poorly differentiated ESCC (P ＜ 0. 01 ). Conclusion Increased expression level of CXCR4 may be a common feature of EADC and ESCC, which is irrelevant to pathological types. CXCR4 level rises at the stage of BE, which is associated with the degree of tumor differentiation, lymph node metastasis and TNM staging. CXCR4 expression is of guiding significance in the diagnosis of BE, EADC and ESCC, and is the potential drug target.