Correlation between macrophage chemotaxis and disease severity in patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To investigate the enhancement of macrophage chemotaxis in patients with knee osteoarthritis (KOA) and its correlation with the disease severity.@*METHODS@#Eighty patients with KOA admitted from July 2019 to June 2022 were enrolled as the observation group and divided into 29 cases of moderate group, 30 cases of severe group and 21 cases of extremely severe group. At the same time, 30 healthy subjects were included as the control group. The gene expressions of NF-κB, CXC chemokine receptor 7 (CXCR7) and CXC chemokine ligand 12 (CXCL12) in macrophages of each group were analyzed. Visual analogue scale(VAS) was used to evaluate the degree of joint pain. Joint function was evaluated by knee Joint Society Scoring system(KSS). Finally, data analysis was carried out.@*RESULTS@#The expression levels of NF-κB, CXCR7 and CXCL12 in moderate group, severe group and extreme recombination group were higher than those in control group. The VAS, the expression of NF-κB, CXCR7 and CXCL12 in the severe group and the extreme recombination group were higher than those in the moderate group, whereas KSS was lower than that in the moderate group. The VAS, expression levels of NF-κB, CXCR7 and CXCL12 in the extremely severe group were higher than those in the severe group, and KSS was lower than that in the severe group (all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with VAS score, but negatively correlated with KSS(all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with the severity of disease. After excluding the influence of traditional factors (gender, age and disease duration), multiple linear regression analysis further showed that the expression levels of NF-κB, CXCR7 and CXCL12 were still positively correlated with the severity of disease(all P<0.01).@*CONCLUSION@#The chemotaxis of macrophages in patients with KOA increased with the aggravation of the disease, and was related to the degree of pain and function impairment.

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.

High Cytoplasmic CXCR4 Expression Predicts Prolonged Survival in Triple-Negative Breast Cancer Patients Treated with Adjuvant Chemotherapy

BACKGROUND: Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy. METHODS: Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalin-fixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome. RESULTS: High cytoplasmic CXCR4 expression was associated with younger age (p = .008), higher histologic grade (p = .007) and lower pathologic stage (p = .045), while high CXCL12 expression was related to larger tumor size (p = .045), positive lymph node metastasis (p = .005), and higher pathologic stage (p = .017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p = .006) and better recurrence-free survival (RFS) (log-rank p = .020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p = .019) and RFS (p = .038) after multivariate analysis. CONCLUSIONS: High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.

Atypical Chemokine Receptor 1 polymorphism cannot be used as an indicator of liver fibrosis progression in Hepatitis C virus positive patients

Background and Objective: Atypical chemokine receptor 1[ACKR1] represents an atypical chemokine receptor that can bind promiscuously to various chemokines. Chemokines play a crucial role to recruit leukocyte subsets migration through the endothelium and into liver against the virus during the progression of hepatitis C virus [HCV] infection. Most HCV positive patients can lead to liver fibrosis. Hyaluronic add [HA], laminin [LN], collagen IV[C-IV] and amino-terminal pro-peptide of Type-Ill pro-collagen [Pill NP]are indices of the extent of liver fibrosis. The aim of this study was to investigate the association between ACKR1 polymorphism and liver fibrosis with these four serum liver markers in HCV positive patients

Methods: From April 2015 to December 2015, a total of 210 patients [109 males and 101 females] with chronic HCV infection at Dalian Infectious Hospital were recruited to participate in this study. ACKR1 genotyping was using TaqMan probes method. HA, LN, C-IV and Pill NP were detected by using diagnostic kits

Results: We compared serum levels of HA, LN, C-IV and Pill NP between FYA/FYA and FYA/FYB patients and the differences were not significant [P=0.905, P=0.298, P=0.880 and P=0.470, respectively]

Conclusions: This study has attempted to elucidate the role of ACKR1 polymorphism in liver fibrosis progression of HCV infection, our results demonstrated that ACKR1 polymorphism is not directly associated with the fibrogenesis in HCV positive patients

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist / Alterações histológicas e inflamatórias no tecido laminar de equinos submetidos ao modelo de laminite por oligofrutose e tratados com um antagonista para CXCR1/2

With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B at 30mg/kg 6, 12, 18, and 24h after oligofructose) and non-treated groups. Laminar biopsies were performed before and 12, 36, and 72h after administering oligofructose. Samples were stained with periodic acid-Schiff (PAS) and scored from 0 to 6 according to epidermal cell and basal membrane changes. The IL-1β, IL-6, and CXCL1 RNA expressions were determined by RT-PCR. Parametric and non-parametric tests were used to compare times within each group (P<0.05). The PAS grades and IL-1β and IL-6 RNA expression increased in the non-treated group, but remained constant in the treated horses. In conclusion, DF1681B therapy reduced laminar inflammation and epidermal deterioration in treated horses. CXCR1/2 blockage should be considered therapeutically for equine acute laminitis.

A expressão de quimiocinas e a infiltração de leucócitos no tecido laminar são característicos de laminite aguda de equinos. O presente estudo avaliou o efeito terapêutico da administração intravenosa de DF1681B , um antagonista seletivo para CXCR1 e CXCR2 (receptores de quimiocinas), em um modelo de laminite equina por oligofrutose. Utilizaram-se doze cavalos sem raça definida, compreendendo quatro machos e oito fêmeas não gestantes, com idade (média ±SD) 7±3,5 anos, pesando 305±35kg e com uma pontuação média de condição corporal de 5±1/9. Os indivíduos elegíveis eram clinicamente saudáveis, sem história prévia de claudicação relacionados ao casco. Após administração de oligofrutose (10g/kg por sonda nasogástrica), os animais foram divididos em dois grupos: tratado (30mg/kg de DF1681B intravenosa, 6, 12, 18 e 24h após a oligofrutose) e não tratado, que recebeu placebo. Biópsias laminares foram realizadas antes e 12, 36 e 72h após a administração de oligofrutose. As amostras foram coradas com ácido periódico de Schiff (PAS) e classificadas de 0-6 de acordo com alterações nas células epidérmicas e na membrana basal. Também determinaram-se as expressões gênicas de IL-1β, CXCL1 e IL-6 por RT-PCR. Testes paramétricos e não paramétricos foram utilizados para comparar os momentos em cada grupo (P<0,05). Estatisticamente, os graus PAS e as expressões de IL-1β e IL-6 se elevaram após a indução no grupo não tratado, mas se mantiveram constantes nos cavalos tratados. Em conclusão, a terapia por DF1681B reduziu a inflamação laminar e a deterioração epidérmica em equinos submetidos ao modelo de intoxicação por oligofructose. O bloqueio de receptores CXCR1/2 deve ser considerado como uma opção terapêutica para prevenção da laminite aguda de equinos.

Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer

BACKGROUND: Tumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment. METHODS: Total 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups. RESULTS: The mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ²=0.432, P=0.013). CONCLUSION: Increased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.

Expression of C-X-C chemokine receptor type 7 in otorhinolaryngologic neoplasms

<p><b>INTRODUCTION</b>C-X-C chemokine receptor type 7 (CXCR7) has recently been characterised as a novel receptor for the C-X-C motif chemokine 12 (CXCL12)/stromal cell-derived factor 1-alpha. CXCR7 has been thought to play an important role in the pathogenesis of chronic rhinosinusitis, angiogenesis and tumour metastasis. The present study aimed to examine the expression of CXCR7 in tissue samples of laryngeal cancer and maxillary sinus carcinoma to determine its role in the development of otorhinolaryngologic neoplasms.</p><p><b>METHODS</b>Samples of otorhinolaryngologic neoplasms were obtained from 17 patients with either nasal polyps (n = 7), laryngeal cancer (n = 5) or maxillary sinus carcinoma (n = 5), and who underwent surgical resection at West China Hospital of Sichuan University. Total RNA was isolated and CXCR7 mRNA expression was examined and quantified by relative real-time reverse transcription polymerase chain reaction. A one-way analysis of variance was performed using SPSS Statistics version 11.0 (SPSS Inc, Chicago, IL, USA) to compare the CXCR7 mRNA levels among the three groups of patients.</p><p><b>RESULTS</b>All samples tested positive for CXCR7 mRNA. The quantitative results showed that the CXCR7 mRNA levels were highest in laryngeal cancer and lowest in maxillary sinus carcinoma neoplasms, although there was no significant difference among the three samples.</p><p><b>CONCLUSION</b>CXCL12 and its receptor CXCR7 may contribute to eosinophilic inflammation in patients with chronic sinusitis and nasal polyps. Our results also suggest that CXCR7 may play a role in the progression, metastasis and angiogenesis of otorhinolaryngologic tumours.</p>

Expression of chemokine receptor CXCR7 in gastric cancer tissues and cell lines / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression status of CXCR7 in gastric cancer tissues and cell lines.</p><p><b>METHODS</b>The expression status of CXCR7 was detected in 35 primary gastric cancer tissues and matched adjacent tissues by immunohistochemistry and RT-PCR. The correlation of CXCR7 expression with the clinicopathological parameters and risk factors of gastric cancer was analyzed. The expression of CXCR7 in gastric cell lines (HGC-27, MGC-803, BGC-823, SGC-7901 and MKN-28) was also detected by immunofluorescence assay.</p><p><b>RESULTS</b>The expression of CXCR7 was significantly higher in gastric cancer tissues than in adjacent tissues (P<0.01). CXCR7 expression was not correlated with age, gender, smoking history, Helicobacter pylori infection, tumor location or the pathological type, but showed a higher expression level in patients with a alcohol-drinking history than in those without (P<0.05). CXCR7 was expressed with variable intensities in the 5 gastric cancer cell lines without correlation with the degrees of cell differentiation; its expression was the highest in SGC-7901 cells, a moderately differentiated human gastric adenocarcinoma cell line.</p><p><b>CONCLUSIONS</b>CXCR7 is highly expressed in gastric cancer tissues with variable intensities in 5 gastric cancer cell lines, suggesting its important role in gastric cancer progression.</p>

Soluble expression and activity evaluation of SDF-1/54R, a specific antagonist of CXCR7 / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a soluble prokaryotic expression vector of the CXCR7-specific antagonist SDF-1/54R and evaluate its activity.</p><p><b>METHODS</b>SDF-1/54r gene amplified by PCR was inserted into the soluble expression vector pET-41a+ engineered with GST fusion tag, and the recombinant vector was transformed into E. coli strain BL21 (DE3). After IPTG induction of E. coli, the expressed recombinant protein was purified with GST affinity chromatography purification system and confirmed by SDS-PAGE and Western blotting assay. The target protein SDF-1/54R was obtained after digestion of the purified product with enterokinase. Breast cancer MCF-7 cells with high expression of CXCR7 was treated with SDF-1/54R and the cell proliferation and metastasis was evaluated with MTT and chemotaxis assays.</p><p><b>RESULTS</b>The target protein SDF-1/54R obtained showed an obvious inhibitory effect on the proliferation and metastasis of MCF-7 cells as confirmed by MTT and chemotaxis assays.</p><p><b>CONCLUSION</b>SDF-1/54R is a good antagonist of CXCR7 and shows a potential value as an effective anti-cancer agent.</p>

Role of adult resident renal progenitor cells in tubular repair after acute kidney injury / 中西医结合学报

Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the field of stem cell research raise hopes for stem cell-based regenerative approaches to treat acute kidney diseases. In this review, the authors summarized the latest research advances of the adult resident renal progenitor cells (ARPCs) on kidney repair, the role of ARPCs on tubular regeneration after acute kidney injury, the current understanding of the mechanisms related to ARPC activation and modulation, as well as the challenges that remain to be faced.

Expression and function of CXCR2, CXCR7 of acute leukemic cells in rat

OBJECTIVE@#To investigate the expression and function of chemokine receptor CXCR2 and CXCR7 in the rat with acute leukemia.@*METHODS@#Flow cytometry and RT-PCR were used to detect the CXCR2, CXCR7 expression on the bone marrow cell surface of the acute leukemia group and the control group.@*RESULTS@#The bone marrow cell surface CXCR2, CXCR7 relative fluorescence intensity of the observation group was significantly higher than the control group (P<0.05). The CXCR7 expression of the extramedullary infiltration group was significantly higher than non-extramedullary infiltration group (P<0.05). The CXCR2, CXCR7mRNA median expression level of the observation group was higher than the control group. The CXCR2 expression and CXCR7 expression of the observation group was positively correlated, and the correlation coefficient was 0.782 (P<0.01).@*CONCLUSIONS@#The chemokine receptor CXCR2 and CXCR7 are highly expressed in acute leukemia, which may be associated with the occurrence of leukemia.

Effects of CXCR7-shRNA lentiviral vector on the growth and invasiveness of human hepatoma carcinoma cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effects of CXCR7 knock-down by CXCR7-shRNA lentiviral vector on the proliferation and invasion of human hepatoma carcinoma cells in vitro.</p><p><b>METHODS</b>CXCR7-shRNA lentiviral vector was transfected into hepatocellular carcinoma HCCLM3 cells. The changes in mRNA and protein expression of CXCR7 in the transfected cells were investigated using real-time PCR and Western blotting, respectively, and MTT assay was employed to assess the cell proliferation changes. In vitro adhesion assay and transwell chamber test were used to observe the adhesion and invasiveness of HCCLM3 cells, respectively.</p><p><b>RESULTS</b>Transfection of HCCLM3 cells with CXCR7-shRNA lentiviral vector resulted in a significantly decreased expression of CXCR7 at both mRNA and protein levels (P<0.01) and obvious suppression of the cell proliferative activity (P<0.05). CXCR7-shRNA also significantly suppressed the invasiveness and adhesion of HCCLM3 cells (P<0.01).</p><p><b>CONCLUSION</b>CXCR7 knock-down can significantly inhibit the proliferation and invasiveness of human hepatoma carcinoma cells in vitro, suggesting the value of CXCR7 as a potential target for hepatoma carcinoma therapy.</p>

Immunohistochemical Expression of CXC Chemokine Receptor 4 and Galectin-3 in Follicular Tumors of Thyroid / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Follicular tumors can present a difficult diagnostic challenge for cytological evaluation and ultrasound findings. Therefore, new methods which could help distinguish follicular adenoma from follicular carcinoma simply and accurately are greatly desired. This study investigated the usefulness of immnunohistochemical expression of CXC chemokine receptor 4 (CXCR4) and galectin-3 as marker of differentiated thyroid carcinomas. MATERIALS AND METHODS: Expression of CXCR4 and galectin-3 were examined immunohistochemically in the 60 paraffin embedded tissues which were already diagnosed as follicular adenoma (n=20), follicullar carcinoma (n=20), and papillary carcinoma (n=20) of thyroid. RESULTS: Galatin-3 was expressed significantly high in follicular carcinoma than follicular adenoma (p=0.022). CXCR4 was also expressed significantly high in follicular carcinoma than follicular adenoma (p=0.027). The sensitivity of CXCR4 and galectin-3 was 70% and 80% and specificity, 65% and 60% for differential diagnosis of follicular tumors. CONCLUSION: An immunohistochemical panel, including galatin-3 and CXCR4, could be useful in the differential diagnosis between follicular adenoma from follicular carcinoma.

CXCR7 in tumorigenesis and progression / 癌症

Chemokines, a family of small cytokines, were initially characterized as proinflammatory chemoattractant cytokines that regulated cell trafficking and adhesion. Today, attention focuses on chemokines because evidence shows that they play a critical role in tumor initiation, promotion, and progression. CXCR7, a seven-transmembrane G-protein-coupled CXC chemokine receptor, has recently been identified as binding with high affinity to chemokines CXCL11 (I-TAC) and CXCL12 (SDF-1). In this review, we highlight the current knowledge about the role of CXCR7 in the biologic processes of cancer, including cancer growth, survival, adhesion, invasion, metastasis, angiogenesis, and progression. The use of peptides, small molecules, antibodies, or small interfering RNA to target CXCR7 shows promise as new potential avenues for the treatment of cancer.