Serum Stromal Cell-derived Factor-1 Research Articles

Serum stromal cell-derived factor-1 concentrations are increased and associated with nonalcoholic fatty liver disease in children with obesity

IntroductionStromal cell-derived factor-1 (SDF-1) is a newly discovered small molecule adipocytokine, and research has shown that it is closely related to the occurrence and development of obesity. However, there are currently few research reports on SDF-1 in childhood obesity and nonalcoholic fatty liver disease (NAFLD), and this study aims to explore the relationship between SDF-1 and obesity related indicators in obese children.MethodsSerum SDF-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data were collected, such as body mass index (BMI), waist and hip circumference, blood pressure, liver enzymes, cholesterol, and fasting insulin. Children with NAFLD or not were evaluated through Color Doppler Ultrasound.ResultsSerum SDF-1 concentrations were significantly higher in obese subjects than in non-obese subjects (P < 0.05), and were elevated in the NAFLD obese subjects than in the non-NAFLD obese subjects (P < 0.05). SDF-1 was positively correlated with BMI, waist-to-hip ratio, systolic blood pressure, body fat percentage (BFP), basal metabolic rate (BMR), alanine transaminase (ALT), aspartate transaminase (AST), glutyltranspeptidase (GT), and homoeostasis model of HOMA-IR, independent of their uric acid (UA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), gender and age. BFP and BMR were associated with the serum SDF-1 concentrations in multivariable linear regression analysis.ConclusionThese results suggest that SDF-1 levels are elevated in obese children and are associated with NAFLD, indicating that SDF-1 may play a role in the development of childhood obesity and metabolic disorders.

Value of four-dimensional computed tomography angiography combined with stromal cell-derived factor-1 for differentiating ruptured intracranial aneurysms and assessing risk of ruptures

Abstract Background: To analyze the value of four-dimensional computed tomography angiography (4D-CTA) combined with stromal cell-derived factor-1 (SDF-1) for differentiating ruptured intracranial aneurysms and assessing the risk of ruptures. Methods: Fifty patients with unruptured intracranial aneurysms and 50 patients with ruptured ones were included in non-rupture group 1 and rupture group 1, respectively. All patients underwent 4D-CTA and 3D-CTA, and the serum SDF-1 level was detected. Non-rupture group 1 was followed up for 12 months. On this basis, the patients with ruptured aneurysms were included in rupture group 2 and those without ruptured aneurysms were assigned to non-rupture group 2. Results: The AUC values of Wn, AR, L, SR, SDF-1 and their combination for the diagnosis of ruptured intracranial aneurysms were all &gt;0.70, especially their combination. Wn, AR, L, and SR were higher in rupture group 2 than those in non-rupture group 2 (P&lt;0.05). The level of SDF-1 in rupture group 2 [(142.48±11.23) μg/L] was higher than that in non-rupture group 2 [(128.03±10.28) μg/L] (P&lt;0.05). Wn, AR, L, SR, and SDF-1 and their combination all had the AUC values of &gt;0.70 for the prediction of ruptured intracranial aneurysms, especially their combination. The CT values of the internal carotid artery and middle cerebral artery and the CT value and noise of brain parenchyma in 4D-CTA were higher than those in 3D-CTA (P&lt;0.05). Conclusions: 4D-CTA combined with SDF-1 can effectively differentiate ruptured intracranial aneurysms and predict the risk of ruptures.

Decreased Serum Stromal Cell-Derived Factor-1 in Patients with Familial Hypercholesterolemia and Its Strong Correlation with Lipoprotein Subfractions.

Stromal cell-derived factor-1 (SDF-1) is a chemokine that exerts multifaceted roles in atherosclerosis. However, its association with hyperlipidemia is contradictory. To date, serum SDF-1 and its correlations with lipid fractions and subfractions in heterozygous familial hypercholesterolemia (HeFH) have not been investigated. Eighty-one untreated patients with HeFH and 32 healthy control subjects were enrolled in the study. Serum SDF-1, oxidized LDL (oxLDL) and myeloperoxidase (MPO) were determined by ELISA. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. Significantly lower serum SDF-1 was found in HeFH patients compared to healthy controls. Significant negative correlations were detected between serum total cholesterol, triglycerides, LDL-cholesterol (LDL-C), apolipoprotein B100 (ApoB100) and SDF-1. Furthermore, serum SDF-1 negatively correlated with VLDL and IDL, as well as large LDL and large and intermediate HDL subfractions, while there was a positive correlation between mean LDL-size, small HDL and SDF-1. SDF-1 negatively correlated with oxLDL and MPO. A backward stepwise multiple regression analysis showed that the best predictors of serum SDF-1 were VLDL and oxLDL. The strong correlation of SDF-1 with lipid fractions and subfractions highlights the potential common pathways of SDF-1 and lipoprotein metabolism, which supports the role of SDF-1 in atherogenesis.

Application value of combined detection of serum IL-6, SDF-1 and CD64 in the diagnosis of early postoperative infection after limb fractures

ABSTRACT Objective. To explore the application value of combined detection of serum interleukin-6 (IL-6), stromal cell-derived factor-1 (SDF-1) and neutrophils CD64 (CD64) in the diagnosis of early postoperative infection after limb fractures. Methods. 419 patients with limb fractures un erwent surgical treatment in our hospital were selected as study subjects, and they were divided into infection group (n = 104) and non-infection group (n = 315) according to postoperative pathological results of puncture to detect the levels of serum IL-6, SDF-1 and CD64 in the two groups on the 1st, 3rd, 5th and 7th day after surgery, and to analyze the clinical diagnostic efficacy of single and combined detection of the three indexes in early postoperative infection after limb fractures by ROC curve. Results. The levels of serum IL-6, SDF-1 and CD64 in infection group were overtly higher than those in non-infection group at different time after surgery (P < 0.05), and the AUC value, specificity and sensitivity of combined detection were higher than those of single diagnosis. In this study, 14 patients in infection group underwent reoperation, 22 patients received conservative treatment in the later period, 6 patients had postoperative muscular dystrophy, and the remaining patients had a good prognosis. Conclusion. Serum IL-6, SDF-1 and CD64 are closely related to the occurrence of early postoperative infection after limb fractures, and their combination is helpful to improve diagnostic accuracy of early postoperative infection and provide effective reference value for the treatment of postoperative infection in orthopedics.

Serum Levels of CXCR4, SDF-1, MCP-1, NF-κB and ERK1/2 in Patients with Skeletal Fluorosis.

C-X-C motif chemokine receptor 4 (CXCR4), stromal cell-derived factor-1 (SDF-1), monocyte chemoattractant protein-1 (MCP-1), extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) affect bone cells and play an important role in bone and joint diseases, but the data on CXCR4, SDF-1, MCP-1, ERK1/2 and NF-κB in the serum of skeletal fluorosis (SF) patients are inconclusive. Thus, according to the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008), we enrolled patients with SF (n = 60) as the SF group and those without SF as the controls (n = 60). Serum levels of CXCR4, SDF-1, MCP-1, ERK1/2 and NF-κB were detected by enzyme-linked immunosorbent assays (ELISAs). Serum SDF-1, CXCR4, MCP-1 and NF-κB levels were significantly higher in the SF group than in the control group. Within the serum of SF patients, CXCR4 and SDF-1 levels were positively correlated with NF-κB levels. There was no correlation between MCP-1 levels and those of ERK1/2 or NF-κB. SDF-1 and CXCR4 may activate the NF-κB pathway, and MCP-1 affects the occurrence and development of SF by regulating osteocytes through other pathways. The SDF-1/CXCR4 axis and MCP-1 signalling pathway provide a new theoretical basis for the occurrence and development of SF.

Association of serum stromal cell-derived factor 1 levels with EZSCAN score and its derived indicators in patients with type 2 diabetes.

Background The aim of the study was to explore whether plasma stromal cell-derived factor 1 (SDF-1) levels are associated with the EZSCAN score and its derived indicators in patients with type 2 diabetes (T2D).Methods From July 2020 to December 2020, a total of 253 patients with T2D were consecutively recruited. Serum SDF-1 levels were measured by sandwich ELISA. EZSCAN test was applied to evaluate the sudomotor function of each patient, and based on the results, EZSCAN score, cardiac autonomic neuropathy risk score (CANRS) and cardiovascular risk score (CVDRS) were calculated by particular algorithms. In addition, other relevant clinical data were also collected.Results With increasing tertiles of serum SDF-1 levels, the CANRS and CVDRS significantly increased (both Pfor trend <0.001), while the EZSCAN score significantly decreased (Pfor trend <0.001). Moreover, serum SDF-1 levels were significantly and positively correlated with the CANRS and CVDRS (r = 0.496 and 0.510, respectively, both P < 0.001), and negatively correlated with the EZSCAN score (r = −0.391, P < 0.001). Furthermore, multivariate linear regression analyses were constructed, and after adjusting for other clinical covariates, serum SDF-1 levels were independently responsible for EZSCAN score (β = −0.273, t = −3.679, P < 0.001), CANRS (β = 0.334, t = 5.110, P < 0.001) and CVDRS (β = 0.191, t = 4.983, P = 0.003).Conclusions SDF-1 levels in serum were independently associated with the EZSCAN score and its derived indicators, such as CANRS and CVDRS in patients with T2D.

Effect of erythropoietin administration on expression of mRNA brain-derived Neutrophic factor, levels of stromal cell-derived Factor-1, and neuron specific enolase in brain injury model SpragueDawley

BackgroundTraumatic brain injury (TBI) is a complicated condition that is the primary cause of death and disability in children and young adults in developed countries. Various kinds of therapy have been carried out in the management of brain injury, one of which is the administration of erythropoietin (EPO). There are not many studies in Indonesia have proven that EPO administration is effective on parameters such as stromal cell-derived factor 1 (SDF-1), brain-derived neurotrophic factor (BDNF mRNA), and neuron-specific enolase (NSE) in brain injury patients. The purpose of this study was to see how EPO affected BDNF mRNA expression, SDF-1 serum levels, and NSE levels in experimental rats with TBI. MethodsThis study was conducted using a rat head injury model. Fifteen rats were randomly assigned to one of three groups: A, B, or C. EPO was administered subcutis with a dose of 30.000 U/kg. Blood samples were taken after brain injury (H0), 12 h (H12), and 24 h (H24) after brain injury. Serum level of SDF-1 and NSE were measured using mRNA BDNF gene expression was measured with Real-Time-PCR, and ELISA. ResultsThis study found EPO increase BDNF mRNA expression in group C at H-12 (7,92 ± 0.51 vs 6.45 ± 0.33) compared to group B, and at H-24 (9.20 ± 0.56 vs 7.22 ± 0.19); increase SDF-1 levels in group C at H-12 (7,56 ± 0,54) vs 4,62 ± 0,58) compared to group B, and at H-24 (11,32 ± 4,55 vs 2,55 ± 0,70); decrease serum NSE levels in group C at H-12 (17,25 ± 2,02 vs 29,65 ± 2,33) compare to group B and at H-24 (12,14 ± 2,61 vs 37,31 ± 2,76); the values are significantly different with p < 0,05. ConclusionEPO may have neuroprotective and anti-inflammatory properties in TBI by increasing mRNA BDNF expression and serum SDF-1 levels, and decrease serum NSE levels.

Correlation between stromal cell-derived factor 1 and the prognosis of transient ischemic attack

Background: Transient Ischemic Attack (TIA) (1) is a neurological dysfunction of transient cerebrovascular ischemia, which is more common in clinical practice. The risk of further progression to ischemic stroke after a higher TIA can be used as a strong early warning signal of cerebral infarction. Objectives: To explore the correlation between stromal cell-derived factor 1 (SDF-1) and the prognosis of TIA. Methods: A number of 65 patients with TIA were collected, the ABCD2 clinical risk prediction score was implemented, relevant tests and nuclear magnetic resonance imaging (MRI) were performed, and the SDF-1 was recorded in serum levels. End-point events were selected in patients after cerebral infarction in the short term. The statistical analysis method was used to evaluate TIA short-term development for the occurrence of cerebral infarction after risk, the severity of serum level of SDF-1, and infarction. Results: Based on the results, the high-risk group, middle-risk group, and low-risk group had statistically significant differences in serum SDF-1 levels (F=3.820; P&lt;0.05). Correlation analysis demonstrated that ABCD2 score was positively correlated with serum SDF-1 (r=0.349; P&lt;0.05). End-point events were included in the occurrence group and not included in the non-occurrence group. The SDF-1 level of the occurrence group was significantly higher than that of the non-occurrence group. Based on the cranial MRI results as the gold standard, the areas under the curve of the receiver operating characteristic curve (ROC) drawn based on the SDF-1, ABCD2 score, SDF-1 combined with the ABCD2 score, and the occurrence of end-point events were obtained at 0.717, 0.697, and 0.762, respectively. The sensitivity and specificity of SDF-1 were reported as 77.8% and 68.1%, respectively. The sensitivity and specificity of the ABCD2 score were 83.3% and 48.9%, respectively. The sensitivity and specificity of SDF-1 combined with the ABCD2 score were 72.2% and 76.6%, respectively. Conclusion: As evidenced by the obtained results, SDF-1 is associated with ABCD2 score risk classification. Patients with high levels of SDF-1 combined with the ABCD2 score have a higher risk of cerebral infarction. Elevated SDF-1 levels may indicate that TIA patients have a poor short-term prognosis and have a certain predictive value for the diagnosis of the risk of ischemic stroke in the short term.

Serum stromal cell-derived factor-1 levels are associated with diabetic kidney disease in type 2 diabetic patients.

The present study was designed to explore whether serum stromal cell-derived factor-1 (SDF-1) levels were associated with diabetic kidney disease (DKD). Serum SDF-1 levels were measured by sandwich ELISA. Patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g for 3 months were identified as having DKD. Among the recruited type 2 diabetic patients, 18.71% (n = 32) were found to have DKD, and the serum SDF-1 levels of these patients were higher than those of patients without DKD (p < 0.05). Serum SDF-1 levels were positively correlated with cystatin C levels, the UACR and DKD incidence (r = 0.330, 0.183 and 0.186, respectively, p < 0.05) and inversely related to eGFR (r = -0.368, p < 0.001). After adjusting for other clinical covariates by multivariate logistic regression analyses, serum SDF-1 levels were found to be an independent contributor to DKD, and the odds ratio (95% confidence interval) was 1.438 (1.041-1.986). Furthermore, receiver operating characteristic analysis revealed that the optimal SDF-1 cutoff value for indicating DKD was 5.609 ng/mL (its corresponding sensitivity was 82.00%, and specificity was 46.90%). Our results demonstrated that serum SDF-1 levels were closely associated with DKD and could be considered a potent indicator for DKD in patients with T2D.

Influence of reaming intramedullary nailing on MSC population after surgical treatment of patients with long bone fracture.

Reamed intramedullary nailing (RIN) is a surgical method of choice for treatment of diaphyseal fractures. This procedure affects the biological environment of bone tissue locally and systemically. This study investigated the influence of RIN on mesenchymal stem cells (MSCs) in patients with long bone fractures. The axis of C-X-C motif chemokine receptor 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) was selected since it is considered as major pathway for MSC homing and migration. Iliac crest bone marrow (IC-BM) samples and blood samples were collected at two different time points. One sample was collected before the RIN (BN) and the other immediately after RIN (AN). BM-MSCs were cultured and RT-qPCR was performed for CXCR4 mRNA levels and ELISA for the SDF-1 sera levels. The experimental study revealed that there was a correlation between the increase of SDF-1 levels in peripheral blood and a decrease in the levels of CXCR4 in MSCs in the IC-BM following RIN. The levels of SDF-1 showed a significant increase in the sera of patients after RIN. In conclusion, the present study is the first providing evidence of the effects of RIN on MSC population via the CXCR4/SDF-1 axis. The levels of serum SDF-1 factor were elevated after RIN while increased levels of SDF-1 in peripheral blood were inversely correlated with the mRNA levels of CXCR4 on BM-MSCs after RIN. Therefore, this study contributes to enlighten the systematic effects of RIN on the population of MSCs at a cellular level.

Stromal cell-derived factor-1 as a serologic biomarker for the diagnosis of colon ischemia with chronic cardiovascular disease.

Colon ischemia (CI) is the most common ischemic disorder of the gastrointestinal tract. Although some markers of CI, such as procalcitonin and alkaline phosphatase, have been reported, few specific serum markers have been identified. We investigated whether serum stromal cell-derived factor-1 (SDF-1) is a specific marker of CI and clarified the relationship between serum SDF-1 level and CI according to a history of combined chronic cardiovascular disease (CVD).We measured SDF-1 level and other serological markers in 84 patients (control, n = 20; CI without chronic CVD, n = 21; chronic CVD without CI, n = 20; CI with chronic CVD, n = 23).Patients with CI were older than those without CI. There were more women in the CI groups than those without CI. At admission, SDF-1 level was significantly higher in patients having CI with chronic CVD (P < .001) than in other groups. SDF-1 level was significantly higher at admission than at discharge in patients having CI with chronic CVD (P < .001) but not in patients having CI without chronic CVD. SDF-1 level did not differ according to symptoms, involved sites, or duration of hospitalization. At a cutoff value of 0.5 pg/mL for the SDF-1 level in patients having CI with chronic CVD, the sensitivity and specificity for SDF-1 were 91.3% and 95%, respectively. The area-under-the-curve (AUC) value was 0.95. In the logistic regression analysis, an elevation of the SDF-1 level to >0.5 pg/mL was a significant indicator of CI with chronic CVD [odds ratio (OR), 114.914; 95% confidence interval, 10.51 to >999.999; P < .001].SDF-1 could be a useful early biomarker for the diagnosis of CI in patients with chronic CVD.

Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model

BackgroundDistraction osteogenesis (DO) is a surgical technique to promote bone regeneration which may require long duration for bone consolidation. Bone marrow-derived mesenchymal stem cells (MSCs) have been applied to accelerate bone formation in DO. However, the optimal time point for cell therapy in DO remains unknown. This study sought to determine the optimal time point of cell administration to achieve early bone consolidation in DO. We hypothesized that the ratio of circulating MSCs to peripheral mononuclear cells and the level of cytokines in serum might be indicators for cell administration in DO.MethodsUnilateral tibial osteotomy with an external fixator was performed in adult Sprague Dawley rats. Three days after osteotomy, the tibia was lengthened at 0.5 mm/12 h for 5 days. At first, 5 rats were used to analyze the blood components at 6 different time points (3 days before lengthening, on the day lengthening began, or 3, 6, 10, or 14 days after lengthening began) by sorting circulating MSCs and measuring serum levels of stromal cell-derived factor 1 (SDF-1) and interleukin 1β. Then, 40 rats were used for cell therapy study. A single dose of 5 × 105 allogeneic MSCs was locally injected at the lengthening site on day 3, 6, or 10 after lengthening began, or 3 doses of MSCs were injected at the three time points. Sequential X-ray radiographs were taken weekly. Endpoint examinations included micro-computed tomography analysis, mechanical testing, histomorphometry, and histology.ResultsThe number of circulating MSCs and serum level of SDF-1 were significantly increased during lengthening, and then decreased afterwards. Single injection of MSCs during lengthening phase (on day 3, but not day 6 or 10) significantly increased bone volume fraction, mechanical maximum loading, and bone mineralization of the regenerate. Triple injections of MSCs at three time points also significantly increased bone volume and maximum loading of the regenerates.ConclusionThis study demonstrated that bone consolidation could be accelerated by a single injection of MSCs during lengthening when the ratio of peripheral MSCs to mononuclear cells and the serum SDF-1 presented at peak levels concurrently, suggesting that day 3 after lengthening began may be the optimal time point for cell therapy to promote early bone consolidation.

Early risk assessment of circulating endothelial progenitor cells and plasma stromal cell-derived factor-1 for nondisabling ischemic cerebrovascular events

BackgroundEndothelial progenitor cells (EPCs) play an important role in ischemic stroke. However, there are few studies on the relationship between EPC and nondisabling ischemic cerebrovascular events. Our aim was to investigate the association of EPCs and SDF-1 (serum stromal cell-derived factor-1) with NICE (nondisabling ischemic cerebrovascular events).MethodsTIA (transient ischemic attack) and minor stroke patients (153 in total) who had an onset of symptoms within 1 day were consecutively collected. 83 of the patients were categorized into the HR-NICE (high-risk nondisabling ischemic cerebrovascular event) group, and 70 of the patients were in the NHR-NICE (non-high-risk nondisabling ischemic cerebrovascular events) group. Adopted FCM (flow cytometry) was used to measure EPCs, taking double-positive CD34/KDR as EPCs. ELISA was used to measure the concentrations of serum SDF-1 and VEGF (vascular endothelial growth factor). By the sequence of admission time, 15 patients were selected separately from the HR-NICE group and NHR-NICE group, and another 15 healthy volunteers were chosen as the NC (Normal Control) group. The MTT method was used to measure the proliferation of EPCs of peripheral blood in all groups, and the Boyden chamber was used to measure the migration of EPCs.ResultsCompared with the NHR-NICE group, the HR-NICE group was older and contained more patients with hypertension and diabetes. Triglyceride, total cholesterol, and low-density lipoprotein in the HR-NICE group were also higher. For factors such as smoking, BMI (body mass index), and HCY (homocysteine), there were no significant differences (P > 0.05). Circulating EPCs, SDF-1, and VEGF in the NHR-NICE group were all higher. According to the multifactor regression analysis, age, hypertension, diabetes, total cholesterol, EPCs, and SDF-1 are independent risk factors for HR-NICE. For EPCs of 48-h isolated cultures, proliferation and migration were observed to be weakened compared with those of the NC group (P < 0.05). EPCs in HR-NICE group had lower proliferation and migration than those in NHR-NICE group (P < 0.01).ConclusionsFor TIA and minor stroke patients, circulating EPCs and serum SDF-1 concentrations can be used to prognose HR-NICE. Factors that lead to high-risk NICE might be relevant to the decrease in proliferation and migration of circulating EPCs.

Implication of increased serum stromal cell-derived factor-1 for primary biliary cholangitis

BackgroundStromal cell-derived factor-1 (SDF-1), also called chemokine (C-X-C motif) ligand 12 (CXCL12), as a chemokine for premature B cells, T cells and monocytes, is detected in liver, pancreas, spleen and heart. However, its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression is unclear. The aim of this study was to determine serum stromal cell-derived factor-1 (SDF-1) level and to explore its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression of PBC. MethodsA total of 60 PBC patients who received liver biopsy, 32 age- and sex-matched patients with chronic hepatitis B (CHB) and 30 age- and sex-matched healthy controls (HC) were recruited. The sera were measured for SDF-1, interleukin-4 (IL-4), interferon gamma (IFN-γ) and IL-17 using multiplex immunoassay. PBC was divided into four histologic stages according to Scheuer's classification. ResultsThe results showed significantly higher median level of serum SDF-1 (median, interquartile (IQR), 1186.96, 1002.05–1471.33 pg/mL) in PBC patients than those with CHB (median, IQR, 740.69,600.30–1239.27 pg/mL) and HC (median, IQR, 738.44, 687.65–879.33 pg/mL) (P < 0.001). There was no significant difference between CHB patients and HC (P = 0.526). The receiver operating characteristic curves (ROC) showed good diagnostic performance of serum SDF-1 for PBC, AMA-positive and -negative PBC. In particular for AMA-negative PBC, the area under ROC was 0.817, with optimal cutoff value of 802.64 pg/mL and the sensitivity of 100%. Serum SDF-1 level was not associated with other immune, inflammatory and fibrotic indicators, including AMA, ANA, anti-gp210, sp100 and centromere antibodies, bilirubin, ALT, AST, ALP, GGT, WBC, neutrophil, lymphocyte, platelet, Neutrophil- (NLR) and platelet-lymphocyte (PLR), AST to ALT ratio, AST to platelet ratio index (APRI) and FIB-4 index (P > 0.05). Also, there was no significant difference for serum SDF-1 among histological stages (P = 0.091). However, Serum SDF-1 level was significantly correlated with serum IL-17 (r = 0.373, P = 0.004), but not with IL-4 (r = 0.110, P = 0.407) and IFN-γ (r = 0.215, P = 0.098) in those with PBC. ConclusionSerum SDF-1 is increased in and may be a potential useful marker for PBC. Moreover, it may be associated with Th17 recruitment and differentiation in PBC. However, serum SDF-1 may not be associated with the progression of PBC.

Mobilization of endothelial progenitor cell in patients with acute ischemic stroke.

Endothelial progenitor cells (EPCs) have important effect in tissue repair in ischemic organs. The present study was conducted to demonstrate the mobilization of EPCs and its possible mechanism after acute ischemic stroke (AIS). A total of 148 individuals were examined, including 106 patients with ischemic stroke and 42 healthy controls. Seventy-one patients with imaging-confirmed AIS were examined at days 1, 7, 14, and 21 after stroke onset. Circulating EPCs were quantified by flow cytometry using CD133 and KDR surface markers. Serum stromal cell-derived factor-1 (SDF-1) concentrations were determined by enzyme-linked immunosorbent assay. Patients with AIS had significantly lower EPC level than that in the controls (0.022±0.013 vs 0.051±0.020; p<0.01). This difference did not remain significant after adjusting for risk factors at multivariate analysis. Blood pressure, triglyceride, low-density lipoprotein (LDL), and fasting blood sugar were inversely correlated with EPC levels (p<0.01). Systolic blood pressure and LDL remained independent predictors of baseline EPC levels. The number of circulating EPCs increased on day 7 after AIS, reached a peak on day 14, and decreased on day 21. The concentration of SDF-1 had similar changes. The increment of EPCs was correlated with the infarct volume (r=0.708; p=0.006) and SDF-1 concentration on day 14 (r=0.714; p<0.001). Baseline EPC level in patients with AIS reflects the cumulative vascular endothelial damage. EPCs could be mobilized into peripheral circulation in response to stroke stress. This mobilization was associated with the increased expression of SDF-1.

Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes.

The feline mammary carcinoma (FMC) is the third most common tumor in cat, sharing many clinicopathological features with human breast cancer and thus, considered a suitable model for comparative oncology. Due to its poor prognosis, further studies are required to improve the diagnostic accuracy and treatment of cats with spontaneous mammary carcinoma. Recently, it was reported that the overexpression of stromal cell-derived factor-1 (SDF-1) has great value in human breast cancer diagnosis, suggesting that diagnostic tools and therapies targeting the SDF-1 ligand can improve the clinical outcome. In this study, we aimed to evaluate if serum SDF-1 levels can also be used as a biomarker of mammary carcinoma in cats and to analyze if serum SDF-1 levels are associated with clinicopathological features, linked to a specific FMC subtype or correlated with the tumor expression of SDF-1 receptor, the chemokine C-X-C motif receptor 4 (CXCR4). Results showed that cats with mammary carcinoma had significantly higher serum SDF-1 levels than healthy controls (p=0.035) and ROC analysis revealed that the best cut-off value to differentiate sick from healthy animals was 2 ng/ml (specificity: 80%; sensitivity: 57%; AUC=0.715). Significant associations were also found between cats with elevated serum SDF-1 concentrations (≥ 2 ng/ml) and HER2-overexpressing mammary carcinomas (Luminal B-like and HER2-positive subtypes, p<0.0001), CXCR4-negative mammary carcinomas (p=0.027), mammary carcinomas with small size (<3 cm, p=0.027) and tumors with low Ki-67 expression (p=0.012). No statistical associations were found between serum SDF-1 levels and overall or disease-free survival. In summary, our results show that serum SDF-1 levels can be used as a biomarker of feline mammary carcinoma, especially in cats with HER2-overexpressing mammary tumors. Data suggest that targeted therapies against the SDF-1 ligand and/or its CXC4 receptor may be effective for the treatment of FMC, as described for human breast cancer, strengthening the concept that spontaneous feline mammary carcinoma is a suitable model for comparative oncology.

SDF-1/CXCL12 and CXCR4 gene variants, and elevated serum SDF-1 levels are associated with preeclampsia

ABSTRACTObjective: We aimed to compare the frequencies of stromal cell-derived factor-1 (SDF-1) 3′A and CXCR4 single-nucleotide polymorphisms (SNPs) and serum SDF-1 levels in patients with preeclampsia (PE).Methods: In total, 89 women with PE and 89 control women were included in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. Enzyme-linked immunosorbent assay method was used to measure serum SDF-1 level.Results: For SDF-1 3′A SNP, the frequency of GA genotype, total number of GA and AA genotypes, and the A allele frequency was higher in PE patients than controls (p = 0.04, 0.023, and 0.029, respectively). For CXCR4 SNP, the frequency of CT genotype, total number of CT and TT genotypes, and the T allele frequency were higher in PE patients than controls (p = 0.04, 0.006, and 0.005, respectively). SDF-1 serum level was detected higher in preeclamptic women compared with controls (p = 0.001). In PE patients, there was no significant association between serum SDF-1 levels and genotypes of SDF-1 3′A SNP. SDF-1 level was significantly higher in patients bearing CXCR4 CT genotype than CC genotype (p = 0.001). Furthermore, SDF-1 levels in patients bearing CT+TT genotype were found higher than that of patients with CC genotypes (p = 0.001).Conclusion: Results of our study suggest that SDF-1 3′A and CXCR4 polymorphisms and elevated serum SDF-1 levels may have a role in the development of PE.

Role of monocyte chemoattractant protein-1, stromal derived factor-1 and retinoic acid in pathophysiology of neuropathic pain in rats.

Chemokines have been recently recognized to play a role in chronic pain syndromes' pathophysiology. This study investigated the role of monocyte chemoattractant protein-1 (MCP-1), stromal cell derived factor-1 (SDF-1), and retinoic acid (RA) as targets for the therapeutic approach of neuropathic pain. A chronic constriction injury (CCI) model of neuropathic pain by unilateral ligation of left sciatic nerve was performed in adult female Wistar rats. The effects of doxycycline (Dox, 50 mg/kg/day i.p. for 7 days), single dose of bicyclam (5 mg/kg i.p.), RA (15 mg/kg/day i.p. for 7 days), and their combination(s) on behavioral tests of nociception (Von Frey filaments; paw pressure test) on days 0, 1, 3, 5, and 7 of operation were studied. Serum concentrations of MCP-1 and SDF-1 were measured by ELISA. Histological examination of the sciatic nerve was investigated. CCI of sciatic nerve significantly induced mechanical allodynia and hyperalgesia and an increase of MCP-1 and SDF-1 serum levels. Dox-treated groups (Dox, Dox+bicyclam, Dox+RA, Dox+bicyclam+RA) and bicyclam-treated groups (bicyclam, Dox+bicyclam, bicyclam+RA, Dox+bicyclam+RA) attenuated CCI-induced behavioral and biochemical changes. RA inhibited CCI-induced mechanical hyperalgesia but produced a time-dependent reversal of allodynia. Histological findings showed degenerative changes of sciatic nerve after CCI that were partially recovered in Dox-treated groups. These findings demonstrate an association between serum MCP-1 and SDF-1 concentrations and behavioral manifestations of neuropathic pain. RA administration decreased neuropathic pain (antihyperalgesic effect) but did not cause any improvement in sciatic nerve tissues, either alone or in combination with chemokine antagonists. Thus, chemokines may serve as potential targets for drug development in neuropathic pain treatment.

Application of chemokine receptor antagonist with stents reduces local inflammation and suppresses cancer growth.

Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients' condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth.

Tachycardia pacing induces myocardial neovascularization and mobilizes circulating endothelial progenitor cells partly via SDF-1 pathway in canines.

Neovascularization plays pivotal role in ischemic heart failure; however, it is unclear in non-ischemic heart failure. Non-ischemic heart failure was induced by chronic rapid right ventricular pacing at 200 beats/min, respectively, for 3 and 6 weeks in 12 dogs. Sham-operation was performed in another 6 dogs as control. Three-week tachycardia pacing could induce mild/moderate heart failure and 6-week pacing could induce severe heart failure. Pan-microvessel density (MVD) was assessed by CD31 and neovascularization density was assessed by CD105. Mean CD31-MVD and CD105-MVD were significantly increased after 3-week pacing. However, CD105-MVD was significantly decreased by 80 % in 6-week pacing group compared with 3-week pacing group, whereas CD31-MVD was only decreased slightly (15 %; P < 0.05). Myocardial proangiogenic factor stromal cell-derived factor 1 (SDF-1), hypoxia-inducible factors 1α (HIF-1α, a transcription factor which could regulate SDF-1 expression), serum SDF-1 levels and circulating EPC mobilization were greatly elevated after 3-week pacing but nearly returned to baseline level after 6-week pacing, which were in accordance with the changes of neovascularization levels assessed by CD105. Angiogenesis and migrating ability of EPCs were enhanced after stimulation of SDF-1, which could be abolished by pretreatment with SDF-1 receptor antagonist AMD3100. In addition, angiogenesis and migrating functions of EPCs were significantly enhanced by the serum from 3-week pacing dogs, but had much weaker response to the serum from 6-week pacing dogs. In conclusion, tachycardia pacing-induced non-ischemic heart failure, promoted myocardial neovascularization and mobilized circulating EPCs, which might be mediated partly through SDF-1 pathway.