Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study.

BACKGROUND: Previous observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function. METHOD: We performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test. RESULTS: The findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW ß = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW ß = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10- 6), eGFRcrea with SCF (IVW ß =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10- 8), eGFRcys with GCSF (IVW ß =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW ß =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW ß =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10- 4). CONCLUSIONS: Our findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.

Impact of ART on dynamics of growth factors and cytokines in primary HIV infection.

Antiretroviral treatment (ART) of Primary HIV Infection (PHI) has demonstrated virological and immunological benefits. The effect of early ART during PHI on the level of growth factors and chemokines modulating immune cell functions remains to be established. The aim of our work was to analyze the dynamics of 27 cytokines, chemokines and growth/regulation factors in plasma of HIV infected patients treated during PHI. Patients with PHI (n = 43) were enrolled before, 24 and 48 weeks after therapy initiation. Quantification of soluble immune mediators was performed in plasma from HIV infected patients and healthy donors (HD, n = 7) by Luminex technology. The cytokines profile was strongly perturbed in primary HIV infected patients when compared to healthy donors (HD). After 48 weeks of ART, some of these factors were restored to HD level (IL-2, IL-5, IL-7, IL-9, IL12p70, TNFα) while others persisted higher than HD (IL-6, IL-10, IL-13). Interestingly, a subset of chemokines, such as IL-8, MCP-1, RANTES and CCL27, and growth factors such as HGF, SCF and GM-CSF, increased during ART, reaching values significantly higher than HD after 48 weeks. Moreover, the G-CSF and MIP-1ß soluble mediators were persistently altered and showed an inverse correlation with the CD4/CD8 T cell ratio. The increase of chemokines with antiviral activity and of growth factors with hematopoietic and immunomodulatory properties may have beneficial effects. Other studies are mandatory to evaluate the effects of long lasting levels of these factors to clarify their possible role in the context of protection/pathogenesis.

Changes and correlations of anti-Müllerian hormone and stem-cell factors in different ovarian reserve patients during GnRH-antagonist protocol and the effects on controlled ovarian hyperstimulation outcomes.

PURPOSE: To explore the changes and correlations of anti-Müllerian hormone (AMH) and stem-cell factors (SCF) in different ovarian reserve patients during controlled ovarian hyperstimulation (COH) and the effects on COH outcomes. METHODS: Serum at six different timepoints during GnRH-antagonist protocol and follicular fluid (FF) on oocyte retrieval day of 52 patients with polycystic ovary syndrome (PCOS), 61 patients with normal ovarian reserve (NOR) and 42 patients with diminished ovarian reserve (DOR) were collected. AMH and SCF were assessed using enzyme-linked immunosorbent assay. RESULTS: During COH, AMH in the PCOS group was the highest, but SCF did the opposite, and serum AMH gradually decreased, while SCF inversely increased. In the PCOS group, SCF on the first and fourth days of gonadotropin (Gn) administration was negative with Gn dosage (r = - 0.362, P < 0.05; r = - 0.344, P < 0.05). In the NOR group, the basal AMH was also negative with Gn dosage (r = - 0.297, P < 0.05) and positive with COH outcomes (number of retrieved oocytes, MII oocytes, and 2PN fertilization) as well as serum SCF after Gn administration. In the DOR group, both AMH and SCF were significantly associated with COH outcomes. Serum AMH in the DOR group after Gn administration and FF AMH showed a negative correlation with SCF. CONCLUSIONS: Serum AMH decreased, while SCF increased during COH. AMH and SCF are effective for Gn time and dosage adjustment and predicting COH outcomes for NOR and DOR patients. In addition, serum AMH in DOR patients after Gn administration and FF AMH has a negative effect on SCF.

IL-18 and Stem Cell Factor affect hematopoietic progenitor cells in HIV-infected patients treated during primary HIV infection.

The impact of early antiretroviral therapy (ART) during Primary HIV Infection (PHI) on the hematopoietic progenitor cells (HPCs) homeostasis is not available. This study aimed to characterize HPCs and their relationship with cytokines regulating progenitors function in ART-treated patients with PHI. We enrolled HIV infected patients treated with ART during PHI. Circulating HPCs, Lymphoid-HPCs (L-HPCs) frequency and plasmatic concentrations of IL-7, IL-18 and Stem Cell Factor (SCF) were analysed at baseline and after 6 months of therapy. ART introduction during PHI restored the decline of L-HPCs, induced a decrease in the level of pro-inflammatory IL-18 cytokine and a parallel increase of SCF. Moreover, L-HPCs frequency positively correlated with IL-18 at baseline, and with SCF after 6 months of therapy, suggesting that different signals impact L-HPCs expansion and maintenance before and after treatment. Finally, the SCF receptor expression on HPCs decreased after early ART initiation. These insights may open new perspectives for the evaluation of cytokine-driven L-HPCs expansion and their impact on the homeostasis of hematopoietic compartment during HIV infection.

Plasma stem cell factor levels are associated with risk of cardiovascular disease and death.

OBJECTIVE: Stem cell factor (SCF) is a key growth factor for several types of stem and progenitor cells. There is experimental evidence that such cells are of importance for maintaining the integrity of the cardiovascular system. We investigated the association between circulating levels of SCF and risk for development of cardiovascular events and death. METHODS: SCF was analysed by the proximity extension assay technique in plasma from 4742 subjects participating in the Malmö Diet and Cancer Study. Cardiovascular events and death were monitored through national registers with a mean follow-up time of 19.2 years. RESULTS: Subjects with high baseline levels of SCF had lower cardiovascular (n = 340) and all-cause mortality (n = 1159) as well as a lower risk of heart failure (n = 177), stroke (n = 318) and myocardial infarction (n = 452). Smoking, diabetes and high alcohol consumption were associated with lower levels of SCF. Single nucleotide polymorphisms in the gene region encoding PDX1 C-terminal inhibiting factor 1 (PCIF1) and matrix metalloproteinase-9 were associated with plasma SCF levels. The highest SCF quartile remained independently associated with a lower risk of a lower risk of cardiovascular [hazard ratio and 95% confidence interval 0.59 (0.43-0.81)] and all-cause mortality [0.68 (0.57-0.81)], heart failure [0.50 (0.31-0.80)] and stroke [0.66 (0.47-0.92)], but not with MI [0.96 (0.72-1.27)] as compared with the lowest quartile when adjusting for traditional cardiovascular risk factors in Cox proportional hazard regression models. CONCLUSIONS: This prospective population-based study demonstrates that subjects with high levels of SCF have a lower risk of cardiovascular events and death. The findings provide clinical support for a protective role of SCF in maintaining cardiovascular integrity.

Association of stem cell factor gene expression with severity and atopic state in patients with bronchial asthma.

BACKGROUND: Bronchial asthma is a chronic inflammatory and remodeling disorder of the airways, in which many cells, cellular elements, and cytokines play important roles. Stem cell factor (SCF) may contribute to the inflammatory changes occurring in asthma. We aimed to show the expression of SCF gene in patients with asthma as a means of diagnosis and its association with severity and atopic state in these patients. METHODS: This study was carried out on 80 subjects, 50 asthmatic patients and 30 age and gender matched healthy control persons. They were subjected to full history taking, general and local chest examination, spirometric measurements (pre and post broncodilators) using a spirometer, serum IgE, and real time PCR for assessment of SCF mRNA expression. RESULTS: This study showed significant difference between the studied groups regarding pulmonary function tests (P < 0.001). Asthmatic patients had significant higher SCF expression compared to control (P < 0.001), also atopic patients vs non atopic (P = 0.03) and severe asthmatic patients vs mild ones (P < 0.001). SCF expression at cut off point (0.528) is sufficient to discriminate asthmatic patients from control while at cut off point (1.84) for discrimination of atopic patients from non-atopic patients and at cut off point (1.395) for discrimination of severe asthmatic patients from mild ones. A significant negative correlation between SCF expression and inhaled steroid while significant positive correlation with serum IgE was found. CONCLUSION: Measuring SCF mRNA expression can be used as an efficient marker for evaluation of atopy and detection of severity of bronchial asthma.

Immune dysregulation in offspring of a bipolar parent. Altered serum levels of immune growth factors at adolescent age.

Immune dysregulation plays a role in the vulnerability for mood disorders. Immune growth factors, such as Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein-2 (IGF-BP2), Epidermal Growth Factor (EGF), IL-7 and sCD25 have repeatedly been reported altered in patients with mood disorders. The aim of this study was to investigate levels of these factors in serum of adolescent bipolar offspring, who have a heightened risk for mood disorder development and to also analyze the data combined with previously published data. Growth factors were assessed by CBA/ELISA in adolescent bipolar offspring (n=96, mean age=16years) and in age- and gender-matched healthy controls (n=50). EGF belonged to a mutually correlating cluster of mainly neurotrophic compounds including S100B and BDNF, which were in general decreased in serum. IL-7, SCF, IGF-BP2 and sCD25, belonged to a different mutually correlating cluster of immune growth factors, which were in general increased: IGF-BP2 significantly in serum of offspring without a mood disorder, IL-7 and SCF in serum of offspring who had experienced a mood episode. This pattern of de- and increases was not different between bipolar offspring that developed or did not develop a mood disorder over time, apart from the IGF-BP2 level, which was near significantly higher in offspring later developing a mood disorder. Correlations with the previously published immune-cellular abnormalities were not found. In conclusion non-affected adolescents at familial mood disorder development risk were characterized by a distinct pattern of a series of compounds operating in a network of hematopoiesis, neurogenesis and inflammation.

Aqueous extract of Phragmitis rhizoma ameliorates myelotoxicity of docetaxel in vitro and in vivo.

BACKGROUND: A variety of anticancer chemotherapeutics induce adverse side effects including myelotoxicity. Dried roots of Phragmites communis Trinius, Phragmitis rhizoma, have been clinically used in traditional folk medicine to relieve various symptoms like fever. In this study, we evaluated the protective effect of the aqueous extract of Phragmitis rhizoma (EPR) against docetaxel-induced myelotoxicity in vitro and in vivo. METHODS: The in vitro myelo-protective effect of EPR was evaluated using the colony forming unit (CFU) assay with hematopoietic progenitor cells. The in vivo efficacy of EPR was evaluated in myelosuppressed C57BL/6 male mice which were induced by repeated intraperitoneal injections of 30 mg/kg docetaxel for 3 times. EPR was orally administered for 4 days to docetaxel-induced myelosuppressed C57BL/6 male mice which were induced by intraperitoneal injection of 30 mg/kg docetaxel for 3 times: Group 1 (vehicle control, n = 10), Group 2 (docetaxel plus vehicle, n = 10), Group 3 (docetaxel plus EPR 30 mg/kg, n = 10), Group 4 (docetaxel plus EPR 100 mg/kg, n = 10) and Group 5 (docetaxel plus EPR 300 mg/kg, n = 10). Whole blood counts were measured automatically, and immune organs were histologically examined. Expression of immunomodulatory cytokines was measured by quantitative real-time polymerase chain reaction or enzyme-linked immunosorbent assay. The toxicity of EPR itself was evaluated in normal human cell lines including IMR-90, foreskin fibroblast and human umbilical vein endothelial cells. The hepatotoxicity of EPR was predicted by multi-parametric assays involving cell viability, caspase 3/7 activity, GSH contents and LDH leakage using the HepaRG hepatic cell line. RESULTS: Co-treatment of EPR or its major component, p-hydroxycinnamic acid, increased the numbers of hematopoietic CFU counts in the docetaxel-induced in vitro myelotoxicity assay system. The in vitro protective effect of EPR against docetaxel toxicity was replicated in a myelosuppressed animal model: white blood cells, neutrophils, lymphocytes and red blood cells rebounded; bone marrow niche and structural integrity of the thymus were preserved; and the expression of immune-stimulating cytokines including IL3, IL6, SCF and GM-CSF was enhanced. Furthermore, EPR and p-hydroxycinnamic acid promoted the proliferation of primary splenocytes and thymocytes. In the toxicity assays, no remarkable signs related with toxicity were observed in all tested normal human cells and HepaRG. CONCLUSIONS: EPR has the potential to ameliorate docetaxel-mediated myelotoxicity in both in vitro and in vivo models. However, the identification of the responsible active components and the precise underlying myelo-protective mechanism of EPR need to be elucidated before novel drug development using EPR can precede.

Plasma SCF/c-kit Levels in Patients with Dipper and Non-Dipper Hypertension.

Objective The aim of this study was to investigate the relationship between peripheral plasma stem cell factor (SCF)/c-kit levels and the types of dipper and non-dipper hypertension in hypertensive patients. Methods This cross-sectional study included newly diagnosed hypertensive patients who underwent 24-hour ambulatory blood pressure monitor (ABPM) between January 2009 and 2012 in Jiangning city. Patients were divided into the dipper group and the non-dipper group according to ABPM measurements. The levels of SCF and its receptor c-kit, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in peripheral blood were measured via enzyme-linked immunosorbent assays. The serum levels of glucose and lipid were examined as well. The levels of SCF/c-kit were compared between the dippers and the non-dippers; and their correlation with 24-hour mean systolic blood pressure (MSBP), 24-hour mean diastolic blood pressure (MDBP), TNF-α and IL-6 were investigated using linear regression analyses statistically. Results A total of 247 patients with newly diagnosed hypertension were recruited into the study, including 116 non-dippers and 131 dippers. The levels of peripheral plasma SCF were higher in non-dipper group (907.1±52.7 ng/L vs. 778.7±44.6 ng/L; t=2.837, P<0.01), and the levels of c-kit were higher in non-dipper group too (13.2±1.7 µg/L vs 9.57±1.4 µg/L; t=2.831, P<0.01). Linear regression analysis revealed that SCF/c-kit levels were significantly positively correlated with MSBP, MDBP, plasma TNF-α, and IL-6 levels (all P<0.01). Conclusions Peripheral plasma SCF/c-kit levels are higher in patients with non-dipper hypertension than those with dipper one, and significantly correlate with 24-hour MSBP, 24-hour MDBP, serum TNF-α and IL-6 levels.

Decreased levels of stem cell factor in subjects with incident coronary events.

BACKGROUND: It has been proposed that vascular progenitor cells play an important role in vascular repair, but their possible clinical importance in cardiovascular disease has not been fully characterized. Vascular endothelial growth factor A, placental growth factor and stem cell factor (SCF) are three growth factors that are important in recruiting vascular progenitor cells. In this study, we investigated the association between the plasma levels of these growth factors and incident coronary events (CEs). METHODS: Levels of the three growth factors were measured using the proximity extension assay technique in baseline plasma samples from 384 subjects with a first CE (mean follow-up 14.0 ± 4.3 years) and 409 event-free control subjects matched by sex and age, as well as in homogenates from 201 endarterectomy specimens. RESULTS: After controlling for known cardiovascular disease risk factors in a Cox regression model, subjects in the lowest SCF tertile had a hazard ratio of 1.70 (95% confidence interval 1.14-2.54) compared with subjects in the highest SCF tertile. Lower SCF levels were also associated with more severe carotid disease, less fibrous atherosclerotic plaques and an increased incidence of heart failure. Expression of the SCF receptor c-kit was demonstrated in the subendothelial layer and fibrous cap of human atherosclerotic plaques. Smokers and subjects with diabetes had decreased levels of SCF compared with control subjects. CONCLUSION: To our knowledge, this is the first clinical study to provide evidence to support a key role for SCF and progenitor cells in vascular repair. We suggest that the SCF-c-kit pathway may be a promising biomarker and therapeutic target in cardiovascular disease.

Stem Cell Factor and Interleukin-31 Expression: Association with IgE among Egyptian Patients with Atopic and Nonatopic Bronchial Asthma.

Bronchial asthma is a chronic inflammatory disorder which remains a significant cause of morbidity. Recently, it has been reported that the stem cell factor (SCF) and interleukin-31 (IL-31) may play a major role in bronchial asthma. The aim of the current study was to study the association of the stem cell factor and interleukin-31 expression with serum immunoglobulin E among Egyptian patients with atopic and nonatopic bronchial asthma. After measuring serum IgE using total enzyme linked immunosorbent assay (ELISA), Ribonucleic acid (RNA) was isolated to determine gene expression of SCF and IL-31 by real-time polymerase chain reaction (PCR). The levels of SCF mRNAs in atopic asthmatic patients' PBMCs were significantly higher than those in controls (p = 0.0001**) and nonatopic asthmatics (p = 0.0001**). There was a high statistical significant difference also with regard to IL-31 between atopic asthmatics and controls (p = 0.0001**) and between them and nonatopic patients (p = 0.014*). There was a strong significant direct correlation between SCF, IL-31 (r = 0.827 and p = 0.0001**) and between both of them and IgE in asthmatics (r = 0.543 and p = 0.0001**) (r = 0.443 and p = 0.0001**), respectively. A direct correlation between SCF, IL-31 and FEV-1/ FVC %, CRP and wheezing existed. These findings suggest that both SCF and IL-31 play an important role in mediating inflammation and enhancing severity of atopic asthma. Augmented inhaled glucocorticoid therapy was associated with significant reductions in SCF and IL-31 mRNA expression as well as improvements in lung function, symptom scores and bronchial hyperresponsiveness to methacholine (PD20) in atopic and nonatopic asthmatics.

Serum Concentration of Growth Factors in Dogs under Different Conditions of Distraction Osteogenesis.

Concentrations of insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), stem cell factor (SCF), vascular endothelial growth factor (VEGF), and transforming growth factor ß1 (TGF-ß1) were measured in the blood serum of dogs subjected to experimental lengthening of shin bones. In animals subjected to shin bone lengthening at a rate of 1 mm/day in 4 steps, the concentrations of SCF and TGF-ß1 significantly increased in the middle of distraction and IGF-1 concentration increased by the end of distraction. In animals subjected to lengthening at a rate of 1.5 mm/day in 6 steps, the levels of IGF-1 and TGF-ß1 significantly increased in the middle of distraction and the concentration of IGF-2 at the end of distraction. In animals subjected to lengthening at a rate of 3 mm/day in 120 steps, the concentrations of IGF-1 and TGF-ß1 significantly decreased in the middle of distraction and concentrations of IGF-1, VEGF, and TGF-ß1 increased by the end of distraction.

Clinical significance of serum thymus and activation-regulated chemokine in gastric cancer: potential as a serum biomarker.

Thymus and activation-regulated chemokine (TARC) can stimulate cancer cell proliferation and migration. The present study evaluated the clinical significance of serum TARC in gastric cancer (GC). We measured serum TARC, macrophage-derived chemokine, monocyte chemotactic protein-1 and stem cell factor (SCF) levels using a chemiluminescent immunoassay along the GC carcinogenesis (normal, high-risk, early GC [EGC] and advanced GC [AGC]) in both training (N = 25 per group) and independent validation datasets (90 normal, 30 high-risk, 50 EGC and 50 AGC). Serum levels were compared among groups using one-way analysis of variance. To evaluate the diagnostic potential of serum TARC for GC, receiver operating characteristic curve and logistic regression analyses were performed. Correlations between serum TARC and GC clinicopathological features were analyzed using Spearman's correlation. In the training dataset, serum TARC correlated with serum MDC, MCP-1 and SCF. However, only serum TARC and SCF were significantly higher in cancer groups than non-cancer groups (P < 0.001). In the validation dataset, serum TARC also increased along the GC carcinogenesis; the AGC group (167.2 ± 111.1 ng/mL) had significantly higher levels than the EGC (109.1 ± 67.7 ng/mL), the high-risk (66.2 ± 47.7 ng/mL) and the normal (67.5 ± 36.2 ng/mL) groups (Bonferroni, all P < 0.001). Receiver operating characteristic curves and logistic regression demonstrated the remarkable diagnostic potential of serum TARC as a single marker (72.0% sensitivity and 71.1% specificity; cutoff point, 0.37; logistic regression) and in a multiple-marker panel (72.6% sensitivity and 88.2% specificity; cutoff point, 0.54). Spearman's correlation showed that serum TARC was closely correlated with tumor size (γs = 0.227, P = 0.028), T-stage (γs = 0.340, P = 0.001), N-stage (γs = 0.318, P = 0.002) and M-stage (γs = 0.346, P = 0.001). Serum TARC is a promising serum biomarker for GC.

Diagnostic value of CD117 in differential diagnosis of acute leukemias.

C-kit receptor (CD117) and its ligand, stem cell factor, play a key role in normal hematopoiesis. It has been demonstrated that its expression extremely increases in leukemias with myeloid commitment. We analyzed findings on CD117 expression together with other myeloid related markers in 203 de novo acute leukemias, referred to Iranian immunophenotyping centers: Iranian Blood Transfusion Organization (IBTO) and Baghiatallah Hospital (BH). All cases were characterized based on the French American British cooperative group (FAB) and European Group for Immunological Classification of Leukemias (EGIL). The cases comprised of 111 acute myeloblastic leukemia (AML), 86 acute lymphoblastic leukemia (ALL), and 6 acute undifferentiated leukemia (AUL). CD117 was positive in 75 % of AML and 50 % of AUL, whereas none of the ALL cases was positive for this marker. Although CD117 was positive in 100 % of M5a cases, no M5b positive was found (p = 0.036). The calculated specificity for myeloid involvement was 100 % for CD117 and CD33, and 98 % for CD13 and CD15 (p < 0.001). The calculated sensitivity for myeloid involvement was 83, 76, 64, and 41 % for CD13, CD117, CD33, and CD15, respectively (p < 0.001). We concluded that CD117 expression is a specific and rather sensitive marker for differential diagnosis between AML and ALL, and except for M5 subtypes, it fails to determine FAB subtypes; lack of expression in M5 can identify M5b. Therefore, it should be included in the routine primary panel for diagnosis of acute leukemias.

Increase in both angiogenic and angiostatic mediators in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease. METHODS AND RESULTS: Sixty-four subjects with IPF and 10 healthy control subjects (60-70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DLCO<40% or>40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both<55% or>55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P=0.0008) as well as those of TSP-1 (P=0.008), irrespective of the severity of the disease as reflected by DLCO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls. CONCLUSIONS: Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.

Serum levels of stem cell factor for predicting embryo quality.

We evaluated whether serum stem cell factor (s-SCF) levels just prior to ovulation induction could indicate the ability to develop a top-quality (TQ) blastocyst by day 5. We investigated patients with normal ovarian reserve (NOR), polycystic ovary syndrome (PCOS), diminished ovarian reserve (DOR), or mild endometriosis. Our pilot research suggests a correlation between s-SCF levels and the ability to form TQ blastocysts in patients with mild endometriosis. This significant statistical difference (p < 0.05) was noted between mild endometriosis patients for whom a TQ blastocyst was obtained and those for whom it was not possible, as measured on the 8th day of stimulation and the day of oocyte retrieval. The mean SCF levels in the serum of these women on the 8th day were at 28.07 (± 2.67) pg/ml for the TQ subgroup and 53.32 (± 16.02) pg/ml for the non-TQ subgroup (p < 0.05). On oocyte retrieval day it was 33.47 (± 3.93) pg/ml and 52.23 (± 9.72) pg/ml (p < 0.05), respectively.

Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin-releasing hormone agonist and antagonists, on follicular fluid stem cell factor and serum urocortin 1 levels on the day of oocyte retrieval.

PURPOSE: To compare the serum and follicular fluid (FF) concentrations of stem cell factor (SCF) as well as the serum urocortin 1 (UCN1) concentration in gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a) protocols for controlled ovarian hyperstimulation (COH) in IVF patients. METHODS: Follicular fluids and blood samples of 42 infertile women undergoing COH for IVF-embryo transfer with either GnRH agonist (n = 22) or GnRH antagonist (n = 20) protocols from 2010 to 2011 were collected during oocyte retrieval. SCF concentrations of serum and FF were assessed by sandwich enzyme immunoassay using ELISA Kit for SCF kid. Serum UCN1 concentration were measured using commercially available enzyme-linked immunosorbent assay. RESULTS: Concentrations of serum UCN1, serum and FF SCF were similar in the two groups. The serum SCF levels correlated strongly with the follicular SCF levels (r = 0.770, p < 0.001). The mean implantation rate, biochemical and clinical pregnancy rate and live birth rate per cycle were also similar in the groups. CONCLUSIONS: These observations suggest that there is no significant difference in follicular microenvironment in terms of SCF and UCN1 between agonist and antagonist protocols.

Serum hematopoietic growth factors as diagnostic and prognostic markers of acute renal allograft rejection: a potential role for serum stem cell factor.

OBJECTIVES: Hematopoietic growth factors (HGFs) are proliferative and chemotactic agents for hematopoietic stem cells, although their functions on renal transplantation are rarely reported. This study aimed to investigate the association of HGFs with acute T cell-mediated renal rejection. EXPERIMENTAL DESIGN: A cytokine bead array was used to analyze 10 HGFs in the sera of 32 patients with acute T cell-mediated renal allograft rejection before and during rejection and after rejection reversal. Stable renal allograft recipients (n=38) were also investigated. RESULTS: Serum levels of stem cell factor (SCF), IL-3, flt3 ligand, G-CSF, M-CSF and GM-CSF were elevated during episodes of rejection compared with before and after rejection. Serum concentrations of SCF, G-CSF, flt3 ligand and IL-3 were significantly higher than in the absence of rejection. Moreover, serum SCF levels were significantly higher in patients before rejection versus stable controls. CONCLUSIONS: HGFs are reported to be involved in acute T cell-mediated renal allograft rejection. A direct correlation was observed between SCF levels and the occurrence of acute renal allograft rejection which may represent an effective diagnostic and predictive biomarker for acute cellular renal allograft rejection.

Circulating concentration of stem cell factor in serum of stimulated IVF patients.

Stem cell factor (SCF) plays a major role in haematopoiesis and spermatogenesis, and possibly female fertility. This study investigated the role of changes in SCF concentrations in 74 assisted conception patients. In group 1 (n=74) SCF concentration was assessed in serum and follicular fluid (FF) on the day of follicular puncture (FP) and compared in serum and FF in response to ovarian stimulation between low (n=25), moderate (n=26) and high (n=14) responders. In group 2 (n=30) serum for SCF assessment was collected throughout the menstrual cycle until gestation. SCF concentration related to the number of follicles in serum and in FF decreased from low to moderate and high responders (P<0.001); pregnancy rates were 20.0%, 34.6% and 50.1%, respectively (P=0.05). SCF in serum increased from stimulation days 6-8 to 9-11 and peaked on the day of human chorionic gonadotrophin injection (P=0.03). The SCF concentrations dropped slightly on the day of FP, increased significantly to the day of pregnancy confirmation and reached highest concentration (P=0.02) during gestation. SCF is involved in follicle development and may be a predictor of IVF outcome.

Diagnostic and prognostic value of stem cell factor plasma level in glioblastoma multiforme patients.

BACKGROUND: Investigation of novel blood-circulating agents as potential biomarkers for glioblastoma multiforme (GBM) patients' diagnosis and monitoring has gained lots of attention, due to limitations of imaging modalities and invasive tissue biopsy procedures. The present study aims to assess the diagnostic and prognostic values of preoperative stem cell factor (SCF) plasma level in GBM patients. METHODS: Preoperative plasma samples from 58 GBM patients and 20 patients with nonglial tumors and 30 healthy controls were obtained. SCF levels were measured by employing the enzyme-linked immunosorbent assay test and the values were compared between these three groups. Then, the association of SCF plasma level and tumor volume, progression-free survival (PFS), and overall survival (OS) for the GBM patients were evaluated. RESULTS: Mean preoperative SCF plasma level of the GBM patients (2.80 ± 1.52 ng/ml) was significantly higher (p < 0.0001) than the healthy controls (0.80 ± 0.24 ng/ml) and patients with nonglial tumor (1.41 ± 0.76 ng/ml). Receiver operating characteristic analysis revealed that the preoperative SCF plasma level could distinguish the GBM patients from healthy controls and patients with nonglial tumors with the area under curve values of 0.915 and 0.790, respectively. However, no significant association was observed between the GBM patients' preoperative SCF plasma levels and tumors' volume (Spearman Rho correlation coefficient, 0.1847; 95% CI, p = 0.1652). The GBM patients were divided into two subgroups based on mean preoperative SCF plasma levels (2.80 ng/ml). No significant difference was observed between the patients' PFS (p = 0.3792) and OS (p = 0.1469) at these two subgroups. CONCLUSION: Taking together, the SCF plasma level can serve as a novel diagnostic blood-circulating biomarker for patients with GBM. However, its plasma level is not correlated with GBM patients' tumor volume, PFS, or OS.