Inflammatory Glycoprotein YKL-40 Is Elevated after Coronary Artery Bypass Surgery and Correlates with Leukocyte Chemotaxis and Myocardial Injury, a Pilot Study.

The aim of the present study was to investigate the levels of YKL-40 during and after coronary artery bypass grafting surgery (CABG) and to establish possible connections between YKL-40 and markers of oxidative stress, inflammation, and myocardial injury. Patients undergoing elective CABG utilizing cardiopulmonary bypass (CPB) were recruited into the study. Blood samples were collected at the onset of anesthesia, during surgery and post-operatively. Levels of YKL-40, 8-isoprostane, interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and troponin T (TnT) were measured by immunoassay. YKL-40 levels increased significantly 24 h after CPB. Positive correlation was seen between post-operative TnT and YKL-40 levels (r = 0.457, p = 0.016) and, interestingly, baseline YKL-40 predicted post-operative TnT increase (r = 0.374, p = 0.050). There was also a clear association between YKL-40 and the chemotactic factors MCP-1 (r = 0.440, p = 0.028) and IL-8 (r = 0.484, p = 0.011) linking YKL-40 to cardiac inflammation and fibrosis following CABG. The present results show, for the first time, that YKL-40 is associated with myocardial injury and leukocyte-activating factors following coronary artery bypass surgery. YKL-40 may be a factor and/or biomarker of myocardial inflammation and injury and subsequent fibrosis following heart surgery.

Prospects of cell chemotactic factors in bone and cartilage tissue engineering.

INTRODUCTION: Tissue engineering has brought hope for the repair of bone and cartilage injury. As potential therapeutic molecules for use in tissue engineering, chemokines promote the development of cell-free tissue engineering, avoiding dilemmas faced by cell-based tissue engineering. The main role of chemokines in tissue engineering is to recruit progenitor/stem cells to the site of damaged tissue in vivo and induce differentiation into the corresponding tissue, thus remodeling tissue function. In recent years, many studies have demonstrated the great potential of chemokines in the regeneration and repair of various tissues, such as heart, bone and cartilage tissue. AREAS COVERED: The classification, structure, and function of chemokines and the application of several common chemokines in diseases, especially in bone/cartilage tissue regeneration are discussed. EXPERT OPINION: Many studies have demonstrated that the combinatory use of cell chemotactic factors (CCFs) and growth factors can exert synergistic effects on chondrogenesis and osteogenesis. With further understanding of biomaterials and the development of powerful bio-fabrication techniques, intelligent biomaterials will be created to meet the requirements for controlled bioactive factor release and biomimetic architecture. Also, a better understanding of the biological cascade reactions and pathways of CCFs is beneficial to guide the design of innovative biomaterials.

The molecular structure and role of LECT2 or CHM-II in arthritis, cancer, and other diseases.

Leukocyte cell-derived chemotaxin-2 (LECT2 or LECT-2), also called chondromodulin II (ChM-II or CHM2) plays a versatile role in various tissues. It was first identified as a chemotactic factor to promote the migration of neutrophils. It was also reported as a hepatokine to regulate glucose metabolism, obesity, and nonalcoholic fatty liver disease. As a secreted factor, LECT2 binds to several cell surface receptors CD209a, Tie1, and Met to regulate inflammatory reaction, fibrogenesis, vascular invasion, and tumor metastasis in various cell types. As an intracellular molecule, it is associated with LECT2-mediated amyloidosis, in which LECT2 misfolding results in insoluble fibrils in multiple tissues such as the kidney, liver, and lung. Recently, LECT2 was found to be associated with the development of rheumatoid arthritis and osteoarthritis, involving the dysregulation of osteoclasts, mesenchymal stem cells, osteoblasts, chondrocytes, and endothelial cells in the bone microenvironment. LECT2 is implicated in the development of cancers, such as hepatocellular carcinoma via MET-mediated PTP1B/Raf1/ERK signaling pathways and is proposed as a biomarker. The mechanisms by which LECT2 regulates diverse pathogenic conditions in various tissues remain to be fully elucidated. Further research to understand the role of LECT2 in a tissue tropism-dependent manner would facilitate the development of LECT2 as a biomarker for diagnosis and therapeutic target.

Relationship between neutrophil chemotactic function and chemokine receptor in the early stage of deep second- and third-degree burns / 中国基层医药

Objective:To investigate the relationship between neutrophil chemotactic function and chemokine receptor in the early stage of deep second- and third-degree burns.Methods:Twenty patients with severe burns (burn group) who received treatment within 6 hours after burns in Yantai Yeda Hospital from January 2019 to June 2020 were included in this study. Twenty healthy controls (healthy group) who concurrently received physical examination in the same hospital were also included. The general data and laboratory examination indexes in each group were analyzed. The correlation between neutrophil chemotactic function and chemokine receptor was evaluated.Results:There were no significant differences in general data between the two groups (all P > 0.05). At 1, 3 and 5 days after admission, the number of neutrophils, the number of white blood cells, and procalcitonin, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor-α levels in the burn group were significantly higher than those in the healthy control groups ( F = 12.56, 13.45, 15.78, 17.83, 22.56, 13.39, 10.82, all P < 0.05). At 1, 3 and 5 days after admission, neutrophil migration distance in the burn group was (1 510.22 ± 108.45) μm, (1 380.90 ± 115.67) μm, (1 026.10 ± 95.48) μm, respectively, which were significantly shorter than (1 944.67 ± 139.20) μM in the healthy control group ( t = 23.44, 25.67, 27.52, all P < 0.05). At 5 days after admission, chemokine receptors 1 and 2 positive rates in the burn group were (47.40 ± 1.76)% and (75.33 ± 2.42)%, respectively, which were significantly lower than (95.24 ± 4.89)% and (97.78 ± 2.10)% in the healthy control groups ( t = 4.92, 5.67, both P < 0.05). Correlation analysis showed that neutrophil migration distance was positively correlated with chemokine receptor expression in patients with deep second- and third-degree burns ( r = 0.72, 0.61, both P < 0.05). Conclusion:Neutrophil chemotactic function and chemokine receptor expression decrease in the early stage of deep second- and third-degree burns.

The calcium sensing receptor (CaSR) promotes Rab27B expression and activity to control secretion in breast cancer cells.

Chemotactic and angiogenic factors secreted within the tumor microenvironment eventually facilitate the metastatic dissemination of cancer cells. Calcium-sensing receptor (CaSR) activates secretory pathways in breast cancer cells via a mechanism driven by vesicular trafficking of this receptor. However, it remains to be elucidated how endosomal proteins in secretory vesicles are controlled by CaSR. In the present study, we demonstrate that CaSR promotes expression of Rab27B and activates this secretory small GTPase via PI3K, PKA, mTOR and MADD, a guanine nucleotide exchange factor, also known as DENN/Rab3GEP. Active Rab27B leads secretion of various cytokines and chemokines, including IL-6, IL-1ß, IL-8, IP-10 and RANTES. Expression of Rab27B is stimulated by CaSR in MDA-MB-231 and MCF-7 breast epithelial cancer cells, but not in non-cancerous MCF-10A cells. This regulatory mechanism also occurs in HeLa and PC3 cells. Our findings provide insightful information regarding how CaSR activates a Rab27B-dependent mechanism to control secretion of factors known to intervene in paracrine communication circuits within the tumor microenvironment.

Macrophage Response to Simulated Solar Radiation in the Development of Human Malignant Melanoma.

Background: IFN-γ is widely debated regarding its purported anti- or pro-tumorigenic properties. We initiated a pilot study of primary malignant melanoma patients to investigate whether macrophage-derived IFN-γ is produced in humans as proposed in murine melanomagenesis models. Methods: Biopsy specimens of fresh-frozen primary melanoma tissue were used to quantify co-localization of IFN-γ, macrophages, lymphocytes, and downstream IFN-γ signatures. Additionally, we analyzed simulated solar radiation (SSR) exposed skin in patients with a history of melanoma versus healthy controls to compare the relative magnitude of macrophage infiltration. Results: Our data identified a subset of tumor infiltrating CD68+ macrophages that co-localized with IFN-γ (Pearson's Correlation = 0.33 ± 0.11) in patients with primary melanoma (Stage 0-III). Additionally, a population of infiltrating CD3+ lymphocytes strongly co-localized with IFN-γ (Pearson's Correlation = 0.57 ± 0.11). Malignant melanoma cells were double positive for downstream IFN-γ response elements, MIG/CXCL9, and phosphorylated STAT-1 (P-STAT-1). Cellular signaling pathways were also observed when we exposed the skin of melanoma patients to SSR. Despite robust CXCL9 expression in the epidermis of SSR-exposed skin of melanoma patients, we observed decreased macrophage infiltration into melanoma patient skin. Conclusion: Peritumoral macrophages in melanoma patient skin produce IFN-γ and melanocytes appear to exhibit in vivo responsiveness to IFN-γ, such as P-STAT-1 and upregulated CXCL9 expression. However, despite producing CXCL9 in response to SSR, the normal skin of melanoma patients demonstrates a weak leukocyte infiltration. Immune-modulatory studies for the prevention or treatment of human malignant melanoma may need to address complex tissue and melanocyte signaling and crosstalk.

[Relationships between serum cystatin C, chemerin levels and subclinical atherosclerosis in type 2 diabetes mellitus patients].

Objective: To investigate the relationships between serum cystatin C (Cys C), chemerin levels and subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Methods: A cross-sectional study was carried out between January 2016 and January 2018, and T2DM patients with carotid intima-media thickness (IMT) less than 1.1 mm were selected as subjects (100 males and 80 females, aged 40-60 years). The brachial-ankle pulse wave velocity (baPWV) ≥ 1 700 cm/s was set as the observation group (subclinical atherosclerosis) and baPWV<1 700 cm/s as the control group (non-subclinical atherosclerosis). Physical and blood examination were performed in both groups. Serum Cys C and chemerin levels were measured and their relationship with subclinical atherosclerosis was analyzed. Results: There was a statistically significant correlation between serum creatinine (r=0.167, P=0.011) and baPWV in the observation group, but not in the control group (r=0.105, P=0.070). Multiple linear regression analysis showed that age, duration of diabetes, serum creatinine, estimated glomerular filtration rate (eGFR), Cys C and chemerin were independently associated with baPWV, while high sensitive C reactive protein (hsCRP) and glycosylated hemoglobin (HbA1c) were not associated with baPWV. The elevation of serum Cys C (ß'=0.393, P=0.003) and chemokine (ß'=0.340, P=0.007) were correlative factors for atherosclerosis. Conclusion: The level of serum Cys C and chemerin is possibly related to the occurrence and development of subclinical atherosclerosis in T2DM patients.

Effect of sitagliptin in the treatment of elderly patients with type 2 diabetes mellitus complicated with coronary heart disease and its influence on Hcy, irisin and chemerin / 中国基层医药

Objective To investigate the effect of sitagliptin in the treatment of elderly patients with type 2 diabetes mellitus complicated with coronary heart disease and its influence on Hcy,irisin and chemerin.Methods From January 2015 to June 2016,600 elderly patients with type 2 diabetes mellitus complicated with coronary heart disease in the Sixth People's Hospital of Cixi were selected and divided into observation group and control group,with 300 cases in each group.The control group received metformin treatment,the observation group was given sitagliptin combined with metformin.Before and after treatment,the blood FBG,HbA1c and BMI,Hcy,irisin and chemerin levels were detected.Results After treatment,the FBG,HbA1 c and BMI levels in the observation group were significantly lower than those in the control group [(6.28 ± 1.43) mmol/L vs.(7.03 ± 1.04) mmol/L,t =5.256;(6.17 ± 1.02) ％ vs.(7.02 ± 0.98) ％,t =7.446;(21.03 ± 2.04) kg/m2 vs.(23.02 ± 1.23) kg/m2,t =14.469] (all P ＜ 0.05).The level of Hcy in the observation group after treatment was significantly lower than that in the control group [(7.48 ± 1.03) μmol/L vs.(10.38 ± 1.74) μmol/L,t =17.868,P ＜ 0.05].After treatment,the blood irisin level in the observation group was significantly higher than that in the control group [(3.28 ± 0.89) μg/mL vs.(2.43 ± 0.38)μg/mL,t =15.213,P ＜ 0.05].After treatment,the chemerin level in the observation group was significantly lower than that in the control group [(210.38 ± 9.84)ng/mL vs.(231.38 ± 10.03)ng/mL,t =24.379,P ＜ 0.05].Conclusion Sitagliptin in the treatment of elderly patients with type 2 diabetes mellitus complicated with coronary heart disease can effectively regulate the levels of Hcy,irisin and chemerin,and improve the curative effect.

Effects of Treponema pallidum on the expression of chemokine ligand 6, 8, 10 in human brain microvascular endothelial cells / 中华皮肤科杂志

Objective To evaluate the effects of Treponema pallidum (T.pallidum) on the expression of chemokine ligands (CXCL) in human brain microvascular endothelial cells (HBMECs).Methods HBMECs were randomly divided into 4 groups,which were treated with viable T.pallidum suspension (T.pallidum group),heat-inactivated T.pallidum suspension (inactivated T.pallidum group),200 μg/L lipopolysaccharide (LPS group) and cell culture medium (blank control group),respectively,for 6,12 and 24 hours.Fluorescence-based quantitative PCR and enzyme-linked immunosorbent assay (ELISA) were performed to determine the mRNA and protein expression of CXCL6,CXCL8 and CXCL10 in HBMECs in the above groups respectively.Transwell migration assay was conducted to evaluate the effects of T.pallidum-stimulated HBMECs on the chemotaxis of human promyelocytic HL-60 leukemia cells (HL-60 cells).Results At 6,12 and 24 hours,the T.pallidum group showed significantly higher mRNA expression of CXCL6,CXCL8 and CXCL10 in HBMECs compared with the blank control group and inactivated T.pallidum group (all P ＜ 0.05),while there were no significant differences between the blank control group and inactivated T.pallidum group (all P ＞ 0.05).Compared with the LPS group,the T.pallidum group showed significantly decreased mRNA expression of CXCL6 and CXCL8 (P ＜ 0.05),but similar mRNA expression of CXCL10(P ＞ 0.05)at 6,12 and 24 hours.At these time points,the levels of CXCL6 and CXCL8 in the culture supernatant of HBMECs were significantly higher in the T.pallidum group than in the blank control group and the inactivated T.pallidum group (all P ＜ 0.05),but no significant differences were observed between the blank control group and the inactivated T.pallidum group (both P ＞ 0.05).Moreover,there were no significant differences in the level of CXCL10 in the culture supernatant of HBMECs among the T.pallidum group,the inactivated T.pallidum group and the blank control group (all P ＞ 0.05).The number of migratory HL-60 cells in the lower Transwell chambers was significantly higher in the T.pallidum group than in the inactivated T.pallidum group and the blank control group (both P ＜ 0.05).Conclusion Viable T.pallidum can up-regulate the gene expression of CXCL6,CXCL8 and CXCL10 in HBMECs,promote the secretion of CXCL6 and CXCL8,and enhance the chemotactic effect of HBMECs on HL-60 cells,which may play a certain role in the occurrence of neurosyphilis.

Effect of rhBNP on serum chemerin and IL-37 levels in acute myocardial infarction patients undergoing emergency PCI / 中华老年心脑血管病杂志

Objective To study the effect of rhBNP on serum chemerin and IL-37 levels in acute myocardial infarction (AMI) patients undergoing emergency PCI.Methods Eighty AMI patients who underwent emergency PCI were randomly divided into cortrol group (n =40) and rhBNP treatment group (n=40).The patients in control group were treated with conventional drugs and those in rhBNP treatment group were treated with intravenous rhBNP.Their serum chemerin and IL-37 levels were measured by ELISA.Their LVEDD and LVEF were compared.Results The serum level of chemerin was significantly lower while that of IL-37 was significantly higher in two groups at 72 h and on day 7 after PCI than before PCI (P＜0.05).The serum level of chemerin was significantly lower while that of IL-37 was significantly higher in rhBNP group than in control group at 72 h and on day 7 after PCI (P＜0.05).The LVEDD was significantly shorter while the LVEF was significantly higher in two groups on day 7 and month 1 after PCI than before PCI (P＜0.05).The LVEDD was significantly shorter in rhBNP group than in control group on day 7 and month 1 after PCI (P＜0.05).Conclusion rhBNP can effectively reduce the serum chemerin level,increase the serum IL-37 level,and improve the cardiac function in AMI patients following emergency PCI.The effect of rhBNP is better than that of conventional drugs in AMI patients after emergency PCI.

Research progress of chemokines and their receptors in hepatocellular carcinoma / 国际外科学杂志

Chemokines and their receptors play an important role in the occurance and development of hepatocellular carcinoma(HCC).The effects of chemokines and their receptors in HCC are different,chemokines and their receptors associated with HCC are mostly expressed in promoting tumor cell proliferation,angiogenesis and invasion,but some chemokines and their receptors play an anti-tumor role.This reviews focus on the role of chemokines and their receptors in HCC.

[Expression profiles and clinical implication of plasma chemokines in patients with Stanford type A aortic dissection].

Objective: To explore the plasma chemokines expressions and related clinical implication in patients with Stanford type A aortic dissection (AD). Methods: We retrospectively analyzed the data of 65 patients with Stanford type A aortic dissection, hypertensive patients and 11 healthy subjects admitted in our department from October 2013 to December 2014, they were divided into four groups: NH-CON group (11 healthy subjects), H-AD group (29 AD patients with hypertension), NH-AD group (21 AD patients without hypertension), and H-CON group (14 hypertension patients). Four plasma samples from AD patients and 4 plasma samples from healthy subjects were collected randomly with random numbers table, and the levels of different chemokines were examined by protein array analysis. Then, plasma levels of chemokines including macrophage inflammatory protein 1ß(MIP-1ß), epithelial neutrophil activating peptide 78(ENA-78), interleukin 16(IL-16), interferon inducible protein 10(IP-10) and FMS-like tyrosine kinase 3(Flt-3) ligand were analyzed by luminex. Pearson analysis was used to determine the correlations between the chemokines and serum C reactive protein (CRP) levels. Results: Plasma levels of MIP-1ß(34.0(29.3, 47.2) ng/L vs. 51.0(28.2, 80.7) ng/L, P<0.05) and ENA-78(110.5(59.1, 161.4) ng/L vs. 475.7(299.3, 837.3) ng/L, P<0.05) were significantly lower in H-AD group, while plasma IL-16 level was significantly higher in H-AD group(54.7(16.3, 187.8) ng/L vs. 17.5(11.9, 20.8) ng/L, P<0.05) than in H-CON group. Plasma levels of MIP-1ß(48.3(26.4, 62.1) ng/L, P<0.05) were significantly lower in H-AD patients than in NH-AD patients. Plasma level of ENA-78 was significantly lower in NH-AD group than in NH-CON group (95.0(58.0, 155.0) ng/L vs. 257.7(85.2, 397.8) ng/L, P<0.05). The levels of IP-10 and Flt-3 ligand were similar among the 4 groups (all P>0.05). Pearson analysis showed that there were no correlation between MIP-1ß(r(2)=0.01, P>0.05), ENA-78(r(2)=0.02, P>0.05), IL-16(r(2)=0.02, P>0.05), IP-10(r(2)=0.00, P>0.05), Flt-3 ligand(r(2)=0.02, P>0.05) and CRP levels in patients with Stanford type A aortic dissection. Conclusions: Lower plasma levels of MIP-1ß and ENA-78 and higher plasma levels of IL-16 may associate with the occurrence and development of type A aortic dissection, but their concentrations are not correlated with serum CRP levels. There is no significant change on plasma levels of IP-10 and Flt-3 in the Stanford type A aortic dissection patients.

Expression profiles and clinical implication of plasma chemokines in patients with Stanford type A aortic dissection / 中华心血管病杂志

Objective@#To explore the plasma chemokines expressions and related clinical implication in patients with Stanford type A aortic dissection (AD).@*Methods@#We retrospectively analyzed the data of 65 patients with Stanford type A aortic dissection, hypertensive patients and 11 healthy subjects admitted in our department from October 2013 to December 2014, they were divided into four groups: NH-CON group (11 healthy subjects), H-AD group (29 AD patients with hypertension), NH-AD group (21 AD patients without hypertension), and H-CON group (14 hypertension patients). Four plasma samples from AD patients and 4 plasma samples from healthy subjects were collected randomly with random numbers table, and the levels of different chemokines were examined by protein array analysis. Then, plasma levels of chemokines including macrophage inflammatory protein 1β(MIP-1β), epithelial neutrophil activating peptide 78(ENA-78), interleukin 16(IL-16), interferon inducible protein 10(IP-10) and FMS-like tyrosine kinase 3(Flt-3) ligand were analyzed by luminex. Pearson analysis was used to determine the correlations between the chemokines and serum C reactive protein (CRP) levels.@*Results@#Plasma levels of MIP-1β(34.0(29.3, 47.2) ng/L vs. 51.0(28.2, 80.7) ng/L, P<0.05) and ENA-78(110.5(59.1, 161.4) ng/L vs. 475.7(299.3, 837.3) ng/L, P<0.05) were significantly lower in H-AD group, while plasma IL-16 level was significantly higher in H-AD group(54.7(16.3, 187.8) ng/L vs. 17.5(11.9, 20.8) ng/L, P<0.05) than in H-CON group. Plasma levels of MIP-1β(48.3(26.4, 62.1) ng/L, P<0.05) were significantly lower in H-AD patients than in NH-AD patients. Plasma level of ENA-78 was significantly lower in NH-AD group than in NH-CON group (95.0(58.0, 155.0) ng/L vs. 257.7(85.2, 397.8) ng/L, P<0.05). The levels of IP-10 and Flt-3 ligand were similar among the 4 groups (all P>0.05). Pearson analysis showed that there were no correlation between MIP-1β(r2=0.01, P>0.05), ENA-78(r2=0.02, P>0.05), IL-16(r2=0.02, P>0.05), IP-10(r2=0.00, P>0.05), Flt-3 ligand(r2=0.02, P>0.05) and CRP levels in patients with Stanford type A aortic dissection.@*Conclusions@#Lower plasma levels of MIP-1β and ENA-78 and higher plasma levels of IL-16 may associate with the occurrence and development of type A aortic dissection, but their concentrations are not correlated with serum CRP levels. There is no significant change on plasma levels of IP-10 and Flt-3 in the Stanford type A aortic dissection patients.

Correlation of SDF-1 and CXCR4 expressions and MVD with the prognosis of multiple myeloma / 肿瘤

Objective: To investigate the expressions of stromal cell-derived factor-1 (SDF-1) and its receptor chemokine (C-X-C motif) receptor 4 (CXCR4) as well as the microvessel density (MVD) in patients with multiple myeloma, and to explore their effects on the prognosis. Methods: The expressions of SDF-1 and CXCR4 as well as MVD in bone marrow fr o m 7 8 p ati e n ts wi thmul tiple m yelom a an d 3 0 norm alperson s wered e te ctedby immunohistochemical method. The correlations of age, gender, international staging system (ISS) staging, immunoglobulin typing, light chain classification, SDF-1 expression, CXCR4 expression and MVD with the prognosis of multiple myeloma patients were analyzed. Results: The expression of SDF-1 in bone marrow of multiple myeloma patients was positively cor re lated wi th th e exp ressionof CXCR4 and the count of MVD (b oth P 0.05). The overall survival rate and progression-free survival rate of multiple myeloma patients with low expressions of SDF-1 and CXCR4 were lower than those of patients with high expressions of SDF-1 and CXCR4 (both P < 0.05). The overall survival rate and progression-free survival rate of patients with multiple myeloma in low count of MVD group were higher than those in the high count of MVD group (both P < 0.05). The age, SDF-1 and CXCR4 expressions, and MVD were independent prognostic factors for the patients with multiple myeloma (all P < 0.05). Conclusion: The expressions of SDF-1 and CXCR4 and the count of MVD were independent prognostic factors for the patients with multiple myeloma. SDF-1, CXCR4 and MVD may play promoting roles in the malignant progression of multiple myeloma, so they are expected to become new targets for the treatment of multiple myeloma in the future.

Inhibiting effect of Duffy antigen receptor for chemokines on growth of lung adenocarcinoma A549 xenografts in nude mice and its possible mechanism / 肿瘤

Objective: To investigate the effects of local injection of Duffy antigen receptor for chemokines (DARC) protein on the growth of lung adenocarcinoma A549 xenografts in nude mice and the angiogenesis in xenograft tumor tissues. Methods: The lung cancer xenograft model was established by using lung adenocarcinoma A549 cells. After xenograft formation, the different doses (l, 10 and 100 ng) of DARC protein were injected into the xenografts as the low, medium and high dose groups, respectively; while 0.9% sodium chloride solution (100

Effects of ARHI gene transfection on chemokines and receptors related gene expression profile of PANC1 cells / 中华胰腺病杂志

Objective To investigate the effects of ARHI transfection on the chemokines and receptors related gene expression profile of PANC1 cells.Methods Plasmids expressing ARHI and empty plasmid were transfected into PANC1 cells, and the stably expressed cell lines were established by using G418.mRNA expression of chemokines and receptors related genes was detected by PCR Array.Real-time PCR was used to detect mRNA expression of the genes related vascular growth.Results In cells transfected with ARHI gene, the expression levels of mRNA of 36 genes were down-regulated, and 9 were up-regulated.Among the genes related to tumor metastasis and invasion CXCL12 and CXCR4 were significantly down-regulated (6 folds).Among the genes related to the localization of distant organ infiltration and latency, CXCL12, CXCR4 and CCR7 were significantly down-regulated,and CXCR5 was slightly down-regulated.Among the gene with tumor immunity,CXCL8,CXCR1 and CCR7 were significantly down-regulated.Gene expression of CXCL1,CXCL8,CXCR4 and CXCR3 detected by Real-time PCR were consistent with PCR array.Conclusions ARHI gene inhibits the expression of chemokines and receptors related to tumor metastasis,angiogenesis and tumor immunity.

Construction of pEGFP-C1-CXCL1 plasmid and detection of its expression in eukaryotic cells / 军事医学

Objective To construct the pEGFP-C1-CXCL1 eukaryotic expression vector and to investigate the effect of CXCL1 on the proliferation of HepG2 cells under endoplasmic reticulum stress ( ERS).Methods Fragments of CXCL1 were obtained from the cDNA library of HepG2 cells before CXCL1 was cloned into a pEGFP-C1 vector for a recombinant plasmid pEGFP-C1-CXCL1 which was screened and identified by PCR and sequence alignment .Then,the recombinant plas-mid of pEGFP-C1-CXCL1 was transfected into human 293 T cell line and the expression of CXCL 1 was detected by fluores-cence microscopy and Western blotting.pEGFP-C1-CXCL1was furhter transfected into HepG2 cells, and CCK8 was used to detect the inhibitory effect of CXCL1 on tumor proliferation induced by TM in hepatocellular carcinoma .Results pEGFP-C1-CXCL1 was vertified by sequencing analysis .Fluorescence microscopy showed that pEGFP-C1-CXCL1 was transfected into 293T.CXCL1 expression was detected by Western blotting .CCK8 showed that TM inhibited tumor proliferation , while overexpression of CXCL1 decreased the inhabitory rate on cell proliferation of HepG 2 cells under ER stress compared to pEGFP-C1 group and the control group .Conclusion A recombinant pEGFP-C1-CXCL1 plasmid is successfully constructed that can be expressed stably in human 293T cells.Overexpression of CXCL1 can effectively reduce the inhabitory rate of HCC cells induced by the ER stress.

Effects of interleukin-34 on the proliferation and chemokines expression of fibroblast-like synoviocytes in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the effects of interleukin (IL)-34 on the proliferation and chemokines expression of fibroblast-like synoviocytes (FLS) in patients with rheumatoid arthritis (RA).Methods RA FLS were isolated and cultured in the presence or absence of IL-34.FLS proliferation was determined by methyl thiazlyl tetrazoliu method (MTT) method.The levels of chemokines from RA FLS supernatant were detected by protein chip AAH-CYT-G1000 assay.The IL-34 receptor (IL-34R) expression on RA FLS was analyzed by flow cytometry (FCM).Statistical analysis between groups was performed by t test.Results Compared to the control group, the proliferation of IL-34-stimulated RA FLS was obviously increased, and up to the maximum at 72 hours.In addition, the levels of chemokines [epithelial neutrohil-activating peptide 78 (ENA-78), IL-8, growth-related oncogene (GRO), macrophage chemoattractant protein-1 (MCP-1)] on RA FLS supernatant in IL-34 stimulated group were significantly elevated than those in the control group [ENA-78: (397.1±8.2) pg/ml, (54.0±2.9) pg/ml (t=127.61, P＜0.01);IL-8:(2 017±36) pg/ml, (778±102) pg/ml (t=36.67, P＜0.01);GRO: (4 935±160) pg/ml, (2 746±188) pg/ml (t=43.60, P＜0.01);MCP-1: (46 798±1 293) pg/ml, (27 813±2 329) pg/ml (t=22.43, P＜0.01)].IL-34R was highly expressed on the RA FLS.Conclusion IL-34 promotes RA FLS proliferation and chemokines expression, which may be one of the important mechanisms involved in the pathogenesis of RA.

Expression and clinical significance of serum chemokines in patients with lung cancer / 国际肿瘤学杂志

Objective To detect the expression levels of multiple serum chemokines including IFN-inducible T cell chemoattractant (ITAC),Fractalkine,macrophage inflammatory protein (MIP)-3α,IL-8,MIP-lα,MIP-1β in patients with lung cancer and explore their association with the clinical characteristics of lung cancer as well as the correlations among these chemokines.Methods Forty newly diagnosed patients with lung cancer and thirty healthy controls were enrolled for detection of the serum levels of 6 kinds of chemokines by Luminex technology.The correlations of clinical characteristics of lung cancer with these chemokines and the correlations among these chemokines were analyzed by SPSS 17.0 software.Results The serum levels [M (QR)] of IL-8,Fractalkine and MIP-3α in patients with lung cancer were 5.16 (4.74),128.45 (141.89),10.31 (8.88) respectively,and 2.01 (0.95),61.46 (74.81),8.08 (5.87) respectively in control group,with significant differences (Z =-4.783,P ＜0.001;Z =-4.046,P ＜0.001;Z =-3.105,P =0.002).The expression of MIP-1β in lung adenocarcinoma was significantly higher than that in squamous carcinoma [18.32 (12.27) vs.13.72 (7.31),Z =-2.212,P =0.027],and of ITAC in squamous carcinoma was significantly higher than that in small cell lung cancer [24.51 (22.48) vs.9.28 (4.85),Z =-2.460,P =0.014].The expressions of MIP-3α and Fractalkine were positively correlated in the two groups (r =0.619,P＜0.001;r=0.766,P＜0.001).Conclusion The expressions of IL-8,Fractalkine and MIP-3α increase significantly in lung cancer patients,and they are may play important roles in metastatic lung cancer.

Chemokines and lung cancer / 国际肿瘤学杂志

Chemokines and chemokine receptors involve in biological activity and pathological process widely.It has been reported that many tumor cells overexpress functional chemokines.In lung cancer,chemo-kines involve in its proliferation,apoptosis,invasion and metastasis.Chemokines and chemokine receptor over-expressed in lung cancer can be used as specific target for pertinent anti-tumor treatment.