Stromal Cell-derived Factor-1 Levels Research Articles

The causal relationship between type 2 diabetes mellitus and isolated REM sleep behavior disorder: results from multivariable and network Mendelian randomization analysis.

To investigate the causal relationship between type 2 diabetes mellitus (T2DM, exposure) and isolated REM sleep behavior disorder (iRBD, outcome). Genome-wide association study (GWAS) data for iRBD comprised 9,447 samples, including 1,061 iRBD cases from the International RBD Study Group. Initially, we performed linkage disequilibrium score regression (LDSC) to explore the genetic correlation between T2DM and iRBD. Then the two-sample univariate MR (UVMR) analysis was conducted to examine the effects of T2DM and blood sugar metabolism-related factors on iRBD. Subsequently, we applied multivariable MR (MVMR) methods to further adjust for confounders. Lastly, we executed a network MR analysis, with cytokines and immune cell characteristics as potential mediators, aiming to investigate indirect effect of T2DM on iRBD. Results from LDSC suggest a genetic correlation between T2DM and iRBD (rg=0.306, P=0.029). UVMR analysis indicates that both T2DM (Odds Ratio [95% Confidence Interval] = 1.19 [1.03, 1.37], P = 0.017) and high blood glucose levels (1.55 [1.04, 2.30], P = 0.032) are risk factors for iRBD. Even after adjusting for confounders in MVMR, the association between T2DM and iRBD remains robust. Finally, results from network MR analysis suggest that T2DM may indirectly promote the development of iRBD by reducing levels of Stromal Cell-Derived Factor 2 in circulation and by increasing BAFF-receptor expression in IgD- CD38- B cells. T2DM may promote the onset of iRBD by influencing immune-inflammatory responses. Our findings provide valuable insights and directions for understanding the pathogenesis of iRBD, identifying high-risk groups, and discovering new therapeutic targets.

Increased serum EGF but not SDF-1 levels are associated with the pathophysiology and development of generalized anxiety disorder

Generalized anxiety disorder (GAD) is a common and persistent mental illness accompanied by uncontrollable worries for daily staff. Physiological, environmental, genetic, and daily stress from surroundings is involved in developing GAD. Here, we aimed to assess the association of stromal cell-derived factor-1 (SDF-1) and epidermal growth factor (EGF) in the pathophysiology of GAD and their role as diagnostic tools. This case-control study recruited 50 GAD patients from the psychiatry department of a tertiary care teaching hospital in Dhaka city and 38 age-sex-matched healthy controls (HCs) from the surrounding areas. A qualified psychiatrist conducted standardized psychiatric interview to diagnose GAD patients and evaluate HCs by applying the diagnostic and statistical manual for mental disorders, 5th edition (DSM-5) and used the GAD-7 scale to assess the severity of the GAD symptoms. After confirming the inclusion and exclusion criteria, we collected 5 ml blood samples from each participant. We measured serum SDF-1 and EGF levels using ELISA techniques. We observed increased serum levels of EGF in GAD patients compared to HCs (5.91 ± 3.90 ng/ml vs. 1.59 ± 1.08 ng/ml; p < 0.001). Also, this increment is positively associated with the severity of GAD in patients (r = 0.479, p = 0.002). The receiver operating characteristic analysis showed good diagnostic performance (AUC 0.869, p < 0.001) with high sensitivity (82.5%), and specificity (81.1%) at cut off value of 2.31 ng/ml. However, we didn’t find significant differences in serum SDF-1 levels between GAD patients and HCs (11.96 ± 4.50 ng/ml vs. 12.70 ± 11.76 ng/ml; p = 0.337). The present study suggests that GAD patients have increased serum EGF levels but not SDF-1 levels compared to HCs and that increased EGF levels are associated with increased GAD symptoms as well. Moreover, EGF levels could serve as a biomarker for GAD However, further interventional studies with larger and homogeneous samples are suggested to confirm and establish these findings.

Comprehensive Analysis of Immune Responses to Neoadjuvant Immunotherapy in Resectable Non-small Cell Lung Cancer.

Neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of early stage non-small cell lung cancer (NSCLC). However, little is known about which patients are likely to benefit most from neoadjuvant immunotherapy. In this study, we performed a multiplatform analysis on samples from resectable NSCLC treated with neoadjuvant immunotherapy to explore molecular characteristics related to immune responses. A total of 17 patients with resectable stage IB-IIIA NSCLC treated with neoadjuvant immunotherapy were included. A multiplex cytokine assay, bulk TCR sequencing in peripheral blood, and multiplexed immunohistochemistry were performed. Low levels of stromal cell-derived factor (SDF)-1alpha at baseline were associated with unfavorable disease-free survival (DFS). Patients with major pathologic response (MPR) showed a decrease in HGF after one cycle of neoadjuvant immunotherapy. An increase in IDO and IP-10 was observed in patients who developed immune-related adverse events (irAEs) after neoadjuvant immunotherapy. There were no correlations between irAEs and MPR or DFS. The MPR group presented a significant decrease in white blood cells and neutrophil count after neoadjuvant immunotherapy. The high peripheral baseline TCR convergence was correlated with MPR and favorable DFS in lung squamous cell carcinoma (LUSC) receiving neoadjuvant immunotherapy. Neoadjuvant immunotherapy led to a significant increase in CD4+, CD8+, and CD8+CD39+ T-cell infiltration in tumor areas. This study suggests the potential roles of cytokines and TCR convergence for predicting ICIs response in resectable NSCLC and LUSC. CD8+CD39+T cells and CD4+ T cells could be involved in the action of neoadjuvant immunotherapy.

The SDF-1/CXCR4 axis is involved in adipose-derived stem cell migration.

Intravenous injection of adipose-derived stem cells (ADSCs) can improve the urinary function of stress urinary incontinence (SUI) model rats and C-X-C chemokine receptor type 4 (CXCR4)-positive ADSCs are found in urethral tissues. The CXCR4 ligand stromal cell-derived factor-1 (SDF-1) is highly expressed in urinary incontinence model rats. In this study, we investigated the involvement of the SDF-1/CXCR4 axis in the homing of ADSCs. ADSCs were isolated from rats and purified. The levels of CXCR4 and CXCR7 were determined by western blot analysis and immunofluorescence assays following stimulation with SDF-1. Hypoxia conditioning was performed to treat the cells in vitro, following which the messenger RNA (mRNA) and protein level of SDF-1, CXCR4, and CXCR7 were estimated. We found that CXCR4 and CXCR7 were expressed in ADSCs at passage zero (P0), P1, and P3, and the expression of both increased after SDF-1 stimulation. The level of expression of the mRNAs and proteins of SDF-1, CXCR4, and CXCR7 in ADSCs was higher after hypoxic conditioning. We then knocked down CXCR4 or CXCR7 using small interfering RNAs and found that the mRNA levels of CXCR4 and CXCR7 were considerably downregulated in the si-CXCR4/7-transfected cells. We also found that the SDF-1/CXCR4 axis was required for the migration of ADSCs. The phosphorylation levels of Janus kinase (JAK), protein kinase B (AKT), andextracellular regulated protein kinase significantly increased in SDF-1-stimulated ADSCs. However, the migration of ADSCs was suppressed when the corresponding specific inhibitors were used to block JAK and AKT signaling or silence CXCR4, whereas no significant change was observed in the migratory ability of ADSCs when the ERK pathway was blocked or CXCR7 was silenced. The SDF-1/CXCR4 axis is involved in the migration of ADSCs and may play a role in the migrate of ADSCs in SUI.

Molecular mechanisms and clinical manifestations of hereditary hemorrhagic telangiectasia

IntroductionHereditary Hemorrhagic Telangiectasia (HHT) is charactered by telangiectasia and arteriovenous malformations (AVMs). Recurrent visceral and mucocutaneous bleeding is frequently reported among HHT patients, while data on the prevalence of thrombosis remains limited. This study aims to describe the clinical manifestations and molecular biological characteristics of HHT patients. MethodsWe conducted a retrospective study at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. A total of 24 HHT patients, observed between January 2019 and December 2023, were included. We recorded the biological, clinical, and therapeutic events, with particular attention to bleeding and thrombotic events. Gene mutation analysis and blood constituent measurements were performed. ResultsThe prevalence of bleeding among all HHT patients was 100 %, while thrombotic events were noted in 41.70 % of cases. Hepatic arteriovenous malformations (HAVMs) were identified in six patients, pulmonary arteriovenous malformations (PAVMs) in five patients, and cerebral arteriovenous malformations (CAVMs) in one patient. For patients with thrombosis, the discontinuation rates were 23.08 % for antiplatelet therapy and 33.33 % for anticoagulant therapy due to the increased risk of bleeding. Genetic mutations related to HHT were present in 16 patients, with ACVRL1 (activin A receptor-like type 1) mutations being the most frequent at 41.67 %, followed by ENG (endoglin) mutations at 20.83 %, and GDF2 (growth differentiation factor 2) mutations at 4.17 %. The incidence of PAVMs was 75.00 % in HHT1 patients with ENG mutations and 20 % in HHT2 patients with ACVRL1 mutations, while HAVMs occurred in 0 % and 40.00 % of these groups, respectively. Patients were divided into non-AVMs and AVMs groups. Compared to normal controls, von Willebrand factor (vWF) activity was significantly increased in all HHT patients (149.10 % vs. 90.65 %, P < 0.001). In the non-AVMs group, the median level of stromal cell-derived factor-1 (SDF-1) was significantly elevated (124.31 pg/mL vs. 2413.57 pg/mL, P < 0.05), while vWF antigen levels were markedly higher in the AVMs group (165.30 % vs. 130.60 %, P = 0.021). Further grouping of HHT patients based on bleeding and thrombosis phenotypes revealed that those with thrombosis had significantly higher median percentages of schistocytes (3.50 % vs. 0 %, P = 0.002), ferritin concentrations (318.50 μg/L vs. 115.50 μg/L, P = 0.001), and lactate dehydrogenase (LDH) levels (437 U/L vs. 105 U/L, P < 0.001). There were no significant differences in the activity of vWF, protein C (PC), protein S (PS), and factor VIII (FVIII) between the two groups. ConclusionThis study highlighted the complex relationship between arteriovenous malformations and genetic mutations in HHT patients. A comprehensive assessment of bleeding and thrombosis risks should be conducted for each HHT patient, additionally, further clinical studies are needed to explore the risk factors for thrombosis and anticoagulant-related bleeding in HHT.

Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure.

Stromal cell derived factor-1 (SDF-1) plays a pivotal role in the recruitment of stem cells to injured livers. However, the changes of SDF-l in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) have yet to be elucidated. To study the SDF-1 changes in patients with HBV-related ACLF. 30 patients with HBV-related ACLF, 27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study. The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction. Immunohistochemical staining was performed to illustrate the expression of SDF-l, CXC receptor 4 (CXCR4) and Ki67. The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays. The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients (both P < 0.05). The expression of SDF-l, CXCR4 and Ki67 from ACLF were the highest among the three groups (all P < 0.01). The serum SDF-l levels in ACLF patients were significantly lower than that in other patients (both P < 0.01). Moreover, in ACLF patients, the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio. In addition, the serum SDF-l levels in survival were significantly lower compared with the non-survivals (P < 0.05). The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722 (P < 0.05). This study provides the SDF-1 changes in patients with HBV-related ACLF. The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.

Distinct circulating cytokine levels in patients with angiography-proven coronary artery disease compared to disease-free controls

BackgroundSystemic inflammation has a critical role in the development of symptomatic coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches. We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free controls as well as according to the severity of the disease. MethodsCase-control study's population consisted of 452 patients who underwent diagnostic invasive coronary angiography due to clinical indications. We measured the serum concentrations of 48 circulating cytokines. Extent of CAD was assessed using the SYNTAX Score in 116 patients. Cytokine differences between groups were tested using Mann-Whitney U test and associations with CAD were explored using a logistic regression model. ResultsOverall, 310 patients had angiographically verified CAD whereas 142 had no angiographically-detected coronary atherosclerosis. In multivariable logistic regression models adjusted for age, sex, hypertension, atrial fibrillation, history of smoking and treatment for diabetes and hyperlipidemia, increased levels of interleukin 9 (OR 1.359, 95%CI 1.046–1.766, p = 0.022), IL-17 (1.491, 95%CI 1.115–1.994, p = 0.007) and tumor necrosis factor alpha (TNF-α) (OR 1.440, 95%CI 1.089–1.904, p = 0.011) were independently associated with CAD. Patients with SYNTAX Score>22 had increased levels of stromal cell-derived factor 1 alfa (SDF-1α), beta-nerve growth factor (β-NGF), IL-3 and decreased level of IL-17 compared to those with score ≤22 when adjusted for smoking and use of beta-blockers. ConclusionsPatients with CAD have distinct circulating cytokine profiles compared to disease-free controls. Distinct cytokines may have pivotal roles at different stages of coronary atherosclerosis. ClinicalTrials.gov Identifier: NCT03444259 (https://clinicaltrials.gov/study/NCT03444259).

Needle-scalpel therapy inhibits the apoptosis of nucleus pulposus cells via the SDF-1/CXCR4 axis in a rat degenerative cervical intervertebral disc model.

As a common disease, cervical spondylosis (CS) results from the degeneration of the cervical intervertebral disc. However, there are still no effective clinical strategies for the treatment of this disease. Needle-scalpel (Ns), a therapy guided by traditional Chinese medicine theory, alleviates intervertebral disc degradation and is widely used in the clinic to treat CS. Stromal cell-derived factor-1 (SDF-1) and its receptor CXC receptor 4 (CXCR4) in nucleus pulposus cells play an important role in CS onset and development. This study aimed to explore whether Ns can relieve pain and regulate the SDF-1/CXCR4 axis in nucleus pulposus cells to inhibit apoptosis, thereby delaying cervical intervertebral disc degradation in a rat model of CS. It was found that the Ns-treated groups exhibited higher mechanical allodynia scores than the model group, and H&E staining, MRI, and scanning electron microscopy revealed that Ns therapy inhibited intervertebral disc degeneration. Additionally, Ns therapy significantly inhibited increases in the RNA and protein expression levels of SDF-1 and CXCR4. Furthermore, these treatments alleviated the apoptosis of nucleus pulposus cells, which manifested as a decline in the proportion of apoptotic nucleus pulposus cells and inhibition of the decrease in the levels of Bcl-2/Bax. These findings indicated that Ns mitigated CS-induced pain, inhibited the apoptosis of nucleus pulposus cells, and alleviated intervertebral disc degeneration in CS rats. These effects may be mediated by specifically regulating the SDF-1/CXCR4 signaling axis. Based on these findings, we conclude that Ns might serve as a promising therapy for the treatment of CS.

Astragalus polysaccharides augment BMSC homing via SDF-1/CXCR4 modulation: a novel approach to counteract peritoneal mesenchymal transformation and fibrosis

PurposeThis study aimed to evaluate the potential of astragalus polysaccharide (APS) pretreatment in enhancing the homing and anti-peritoneal fibrosis capabilities of bone marrow mesenchymal stromal cells (BMSCs) and to elucidate the underlying mechanisms.MethodsForty male Sprague-Dawley rats were allocated into four groups: control, peritoneal dialysis fluid (PDF), PDF + BMSCs, and PDF + APSBMSCs (APS-pre-treated BMSCs). A peritoneal fibrosis model was induced using PDF. Dil-labeled BMSCs were administered intravenously. Post-transplantation, BMSC homing to the peritoneum and pathological alterations were assessed. Stromal cell-derived factor-1 (SDF-1) levels were quantified via enzyme-linked immunosorbent assay (ELISA), while CXCR4 expression in BMSCs was determined using PCR and immunofluorescence. Additionally, a co-culture system involving BMSCs and peritoneal mesothelial cells (PMCs) was established using a Transwell setup to examine the in vitro effects of APS on BMSC migration and therapeutic efficacy, with the CXCR4 inhibitor AMD3100 deployed to dissect the role of the SDF-1/CXCR4 axis and its downstream impacts.ResultsIn vivo and in vitro experiments confirmed that APS pre-treatment notably facilitated the targeted homing of BMSCs to the peritoneal tissue of PDF-treated rats, thereby amplifying their therapeutic impact. PDF exposure markedly increased SDF-1 levels in peritoneal and serum samples, which encouraged the migration of CXCR4-positive BMSCs. Inhibition of the SDF-1/CXCR4 axis through AMD3100 application diminished BMSC migration, consequently attenuating their therapeutic response to peritoneal mesenchyme-to-mesothelial transition (MMT). Furthermore, APS upregulated CXCR4 expression in BMSCs, intensified the activation of the SDF-1/CXCR4 axis’s downstream pathways, and partially reversed the AMD3100-induced effects.ConclusionAPS augments the SDF-1/CXCR4 axis’s downstream pathway activation by increasing CXCR4 expression in BMSCs. This action bolsters the targeted homing of BMSCs to the peritoneal tissue and amplifies their suppressive influence on MMT, thereby improving peritoneal fibrosis.

SDF-1/CXCR4 axis participants in the pathophysiology of adult patients with moyamoya disease

BackgroundMoyamoya disease (MMD) is characterized by an abundance of moyamoya vessels; however, the precise mechanism driving the spontaneous angiogenesis of these compensatory vessels remains unclear. Previous research has established a link between the stromal cell-derived factor-1 (SDF-1)/ CXC receptor 4 (CXCR4) axis and angiogenesis under hypoxic conditions. Nevertheless, the alterations in this axis within the cerebrospinal fluid, arachnoid membranes and vascular tissue of MMD patients have not been fully investigated. MethodsOur study enrolled 66 adult MMD patients and 61 patients with atherosclerotic vascular disease (ACVD). We investigated the SDF-1 concentration in cerebrospinal fluid (CSF) and CXCR4 expression level on the arachnoid membranes and vascular tissue. We utilized enzyme-linked immunosorbent assay and immunohistochemistr. Additionally, we cultured and stimulated human brain microvascular endothelial cells (HBMECs) and smooth muscle cells (SMCs) under oxygen and glucose deprivation (OGD) conditions followed by reoxygenation, to examine any changes in the SDF-1/CXCR4 axis. ResultsThe results demonstrated an elevation in the level of SDF-1 in CSF among MMD patients compared to those with ACVD. Moreover, the expression of CXCR4 in arachnoid membranes and vascular tissue showed a similar trend. Furthermore, the content of CXCR4 in HBMECs and SMCs increased with the duration of ischemia and hypoxia. However, it was observed that the expression of CXCR4 decreased at OGD/R 24h compared to OGD 24h. The temporal pattern of SDF-1 expression in HBMECs and SMCs mirrored that of CXCR4 expression. ConclusionThese findings indicate a critical role for the SDF-1/CXCR4 axis in the angiogenesis of moyamoya disease.

Photobiomodulation preconditioned diabetic adipose derived stem cells with additional photobiomodulation: an additive approach for enhanced wound healing in diabetic rats with a delayed healing wound.

In this preclinical investigation, we examined the effects of combining preconditioned diabetic adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation (PBM) on a model of infected ischemic delayed healing wound (injury), (IIDHWM) in rats with type I diabetes (TIDM). During the stages of wound healing, we examined multiple elements such as stereology, macrophage polarization, and the mRNA expression levels of stromal cell-derived factor (SDF)-1α, vascular endothelial growth factor (VEGF), hypoxia-induced factor 1α (HIF-1α), and basic fibroblast growth factor (bFGF) to evaluate proliferation and inflammation. The rats were grouped into: (1) control group; (2) diabetic-stem cells were transversed into the injury site; (3) diabetic-stem cells were transversed into the injury site then the injury site exposed to PBM; (4) diabetic stem cells were preconditioned with PBM and implanted into the wound; (5) diabetic stem cells were preconditioned with PBM and transferred into the injury site, then the injury site exposed additional PBM. While on both days 4, and 8, there were advanced histological consequences in groups 2-5 than in group 1, we found better results in groups 3-5 than in group 2 (p < 0.05). M1 macrophages in groups 2-5 were lower than in group 1, while groups 3-5 were reduced than in group 2 (p < 0.01). M2 macrophages in groups 2-5 were greater than in group 1, and groups 3-5 were greater than in group 2. (p ≤ 0.001). Groups 2-5 revealed greater expression levels of bFGF, VEGF, SDF- 1α, and HIF- 1α genes than in group 1 (p < 0.001). Overall group 5 had the best results for histology (p < 0.05), and macrophage polarization (p < 0.001). AD-MSC, PBM, and AD-MSC + PBM treatments all enhanced the proliferative stage of injury repairing in the IIDHWM in TIDM rats. While AD-MSC + PBM was well than the single use of AD-MSC or PBM, the best results were achieved with PBM preconditioned AD-MSC, plus additional PBM of the injury.

Transplantation of induced pluripotent stem cells-derived cardiomyocytes combined with modified Taohong Siwu decoction improved heart repair after myocardial infarction

ObjectiveThis study aimed to study whether modified Taohong Siwu decoction (MTHSWD) combined with human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs) transplantation can promote cardiac function in myocardial infarction (MI) nude mouse model and explore its possible mechanism. MethodsThe MI mouse model was established by the ligation of left anterior descending coronary artery. After 4 weeks of gavage of MTHSWD combined with iPS-CMs transplantation, the changes in heart function of mice were examined by echocardiography. The histological changes were observed by Masson's trichrome staining. The survival and differentiation of transplanted cells were detected by double immunofluorescence staining of human nuclear antigen (HNA) and cardiac troponin T (cTnT). The number of c-kit-positive cells in the infarct area were evaluated by immunofluorescent staining. The levels of stromal cell-derived factor 1 (SDF-1), stem cell factor (SCF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor in infarcted myocardium tissues were detected by ELISA. ResultsMTHSWD combined with iPS-CMs transplantation can improve the heart function of MI mice, reduce the infarct size and collagen deposition in infarct area. By immunofluorescence double-label detection of HNA and cTnT, it was found that MTHSWD combined with iPS-CMs transplantation can improve the survival and maturation of iPS-CMs. In addition, MTHSWD combined with iPS-CMs transplantation can activate more endogenous c-kit positive cardiac mesenchymal cells, and significantly increase the content of SDF-1, SCF and VEGF in myocardial tissues. ConclusionsThe combination of MTHSWD with iPS-CMs transplantation promoted cardiac function of nude mice with MI by improving the survival and maturation of iPS-CMs in the infarct area, activating the endogenous c-kit positive cardiac mesenchymal cells, and increasing paracrine.

Silencing of transient receptor potential canonical channel 4 inhibits endothelial progenitor cell angiogenesis by suppressing VEGF and SDF-1.

Endothelial progenitor cells (EPCs) play a crucial role in acquired angiogenesis and endothelial injury repair. Transient receptor potential canonical channel 4 (TRPC4), a key component of store-operated calcium channels, is essential for EPC function. While the role of TRPCs has been clarified in vascular diseases, the relationship between TRPC4 and EPC function, along with the underlying molecular mechanisms, remains unclear and requires further elucidation. EPCs were isolated from canine bone marrow and identified by morphology and flow cytometry. TRPC4 was transfected into EPCs using lentivirus or negative control, and its expression was assessed using real-time polymerase chain reaction (RT-PCR). Proliferation, migration, and tube formation were evaluated using Cell Counting Kit-8 (CCK-8), Transwell, and Matrigel assays, respectively. Levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) were measured using enzyme-linked immunosorbent assay (ELISA). TRPC4 mRNA expression was significantly reduced in TRPC4-short hairpin RNA (shRNA) transfected EPCs compared to the normal control (NC)-shRNA groups. Migration and tube formation were significantly decreased after TRPC4 silencing, while proliferation showed no difference. Additionally, levels of SDF-1 and VEGF in EPCs were markedly reduced following TRPC4 silencing. TRPC4 plays a crucial role in regulating angiogenesis in EPCs. Silencing of TRPC4 can lead to decreased angiogenesis by inhibiting VEGF and SDF-1 expression, suggesting that TRPC4 knockdown might be a novel therapeutic strategy for vascular diseases.

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.

Correlations of Serum Retinol-Binding Protein and Stromal Cell-Derived Factor-1 with Renal Function in Patients with Diabetic Kidney Disease.

The aim is to investigate the correlations of serum retinol-binding protein (RBP) and stromal cell-derived factor-1 (SDF-1) with renal function in patients with diabetic kidney disease (DKD). A total of 438 patients with type 2 diabetes mellitus (T2DM) treated from October 2017 to October 2020 were enrolled in this prospective study and divided into simple T2DM and DKD groups. According to urinary albumin-to-creatinine ratio (UACR), DKD patients were divided into moderate, severe, and nephrotic groups. They were assigned to one of the following categories of estimated glomerular filtration rate (eGFR): G1, G2, G3a, G3b, G4, and G5 stages. The correlations of RBP and SDF-1 with renal function were analyzed. The DKD group had a longer T2DM course and higher RBP, uric acid (UA), blood urea nitrogen (BUN), β2-microglobulin (β2-MG), serum creatinine (Scr) levels and UACR, and lower SDF-1 level and eGFR than those of simple T2DM group (p < 0.05). The areas under the receiver operating characteristic curves of RBP and SDF-1 for identifying DKD were 0.903 and 0.868, and the optimal cutoff values were 70.71 mg/L and 5.69 ng/mL, respectively. With increasing urinary albumin and clinical stage, RBP, UA, BUN, β2-MG and Scr levels and UACR significantly rose, while SDF-1 level and eGFR declined (p < 0.05). In patients with DKD, RBP was correlated positively with UACR, UA, BUN, β2-MG, and Scr (r = 0.764/0.787/0.693/0.577/0.801, p < 0.0001), and negatively with eGFR (r = -0.782, p < 0.0001). SDF-1 was correlated negatively with UACR, UA, BUN, β2-MG and Scr (r = -0.744/-0.794/-0.666/-0.605/-0.820, p < 0.0001), and positively with eGFR (r = 0.767, p < 0.0001). The multiple linear regression equation was RBP = 29.852 + 0.007 x UACR + 0.101 x UA + 0.497 x BUN + 0.034 x Scr-0.083 x eGFR (p < 0.001). RBP and SDF-1 can identify DKD in patients with T2DM, and the degree of renal function damage is correlated positively with RBP and negatively with SDF-1. Elevated levels of UA, BUN, Scr and UACR as well as reduced eGFR are risk factors for evaluating RBP.

Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults.

Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults. This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay. After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012). These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

Relationship between promoting effect of Zuogui Pills on angiogenesis of reproductive organs and mobilization factors GM-CSF, SDF-1, and their receptors of EPCs in early-aging rats

This study aimed to investigate the relationship between the promoting effect of Zuogui Pills on ovarian and vaginal angiogenesis in early-aging rats and mobilization factors granulocyte-macrophage colony-stimulating factor(GM-CSF), stromal cell-derived factor-1(SDF-1), and their receptors of endothelial progenitor cells(EPCs) and explore the mechanism of Zuogui Pills in improving reproductive hypofunction in early-aging rats. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was used to analyze the chemical components of the extract of Zuogui Pills. Forty 14-month-old female early-aging rats with estrous cycle disorder were randomly divided into a blank group, a conjugated estrogen group(conjugated estrogen suspension, 65 μg·kg~(-1)), and low-(11 g·kg~(-1)) and high-dose(33 g·kg~(-1)) Zuogui Pills groups, with 10 rats in each group. In addition, 10 4-month-old female rats were assigned to the youth control group. The rats in the blank group and the youth control group were treated with 20 g·kg~(-1) distilled water by gavage, while those in the groups with drug intervention were treated with corresponding drugs by gavage, once a day for 15 days. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of SDF-1 and GM-CSF in the mobilization of EPCs in serum. Hematoxylin-eosin(HE) staining was used to observe the changes in the number of ovarian follicles at all levels and corpus luteum, the number of vaginal epithelial layers, the number of vaginal folds, and the blood vessels of ovarian and vaginal tissues in the groups with drug intervention. Western blot was used to detect the expression of ER, GM-CSFR, CXCR4, and CXCR7 proteins in ovarian and vaginal tissues. As revealed by the results, the blank group showed decreased number of corpus luteum, gro-wing follicles at all levels, and blood vessels(P&lt;0.05), decreased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal folds, and the number of vessels in the lamina propria(P&lt;0.05), reduced content of SDF-1 and GM-CSF in the peripheral blood(P&lt;0.05), and down-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P&lt;0.05). The groups with drug intervention showed increased number of growing follicles at all levels, corpus luteum, and blood vessels(P&lt;0.05), decreased number of atresia follicles(P&lt;0.05), increased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal mucosal folds, and the number of blood vessels in the lamina propria(P&lt;0.05), increased content of SDF-1 and GM-CSF in the peripheral blood(P&lt;0.05), and up-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P&lt;0.05). This experiment suggests that Zuogui Pills may promote ovarian and vaginal angiogenesis and improve the reproductive function of early-aging rats by up-regulating the levels of mobilization factors SDF-1, GM-CSF, and their receptors of EPCs.

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.

Mental Stress-Induced Change in Plasma Stromal Cell-Derived Factor-1 and Adverse Cardiovascular Outcomes: A Cohort Study

BackgroundAcute psychological stress can provoke mental stress-induced myocardial ischemia (MSIMI) in coronary artery disease (CAD). Stromal cell-derived factor 1 (SDF1) is released in response to hypoxia, and higher levels of SDF1 are associated with adverse outcomes. We examined whether an increase in SDF1 level in response to mental stress predicts adverse outcomes in CAD patients. MethodsA total of 554 patients with stable CAD (mean age 63 years; 76% male; 26% Black) underwent standardized mental stress testing. Plasma SDF1 levels were measured at rest and 90 minutes after mental stress, and MSIMI was evaluated by 99mTc-sestamibi perfusion imaging. Participants were followed for 5 years for the primary endpoint of composite of death and myocardial infarction (MI) and the secondary endpoint of composite of death, MI, and heart failure hospitalization. Cox hazard models were used to assess the association between SDF1 change and incident adverse events. ResultsMean (standard deviation) SDF1 change with mental stress was +56.0 (230) pg/mL. During follow-up, a rise of 1 standard deviation in SDF1 with mental stress was associated with a 32% higher risk for the primary endpoint of death and MI (95% confidence interval, 6%-64%), independent of the resting SDF1 level, demographic and clinical risk factors, and presence of ischemia. A rise of 1 standard deviation in SDF1 was associated with a 33% (95% confidence interval, 11%-59%) increase in the risk for the secondary endpoint, independent of the resting SDF1 level, demographic, and clinical risk factors and presence of ischemia. ConclusionsAn increase in SDF1 level in response to mental stress is associated with a higher risk of adverse events in stable CAD, independent of MSIMI.

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.