SDF-1α Levels Research Articles

Photobiomodulation inhibits retinal degeneration in diabetic mice through modulation of stem cell mobilization and gene expression.

The number of people suffering from type 2 diabetes (DM2) is increasing and over 30 percent of DM2 patients will develop diabetic retinopathy (DR). Available therapeutic approaches for DR have their limitations. It is of great significance to search for other effective alternate therapeutic approaches. The present study aimed to explore the beneficial effects of photobiomodulation (PBM) on the diabetic retinopathy and underlying mechanisms. Streptozotocin was administered to male mice to establish diabetic model. The mice in the diabetic group (DM) received no treatment, and the mice in DM+PBM group received LED illumination (wavelength 670nm) once a day for 20 consecutive weeks. Retinal vessel degenerate changes, the expression levels of E-Cadherin, N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α in retina, the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 were determined. PBM could significantly inhibit the degenerative change of diabetic retinal vessels, decrease the expression levels of E-Cadherin and N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α and increase VEGF mRNA levels in retina. PBM could also increase the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 in diabetic mice. PBM at 4min/day for 20 consecutive weeks significantly inhibit the degenerative change of diabetic retinal vessels, and PBM is likely to produce its beneficial effects on the retina through promoting the migration of bone marrow stem cells to circulation and diabetic retinal tissue. The present study provides a new therapeutic direction and experimental foundation for the treatment of diabetic retinopathy.

Serum stromal cell-derived factor 1α as a prognostic indicator in elderly patients with acute myeloid leukemia receiving CAG-based chemotherapy.

Stromal-cell-derived factor 1 (SDF-1) plays a crucial role in hematopoiesis and has been implicated in acute myeloid leukemia (AML) pathogenesis. Understanding its relationship with chemotherapy outcomes could lead to improved therapeutic approaches for elderly AML patients. This study retrospectively analyzed the medical records of elderly AML patients (n = 187) and compared serum SDF-1α levels with age-matched controls (n = 120). Patients received CAG (cytarabine, aclarubicin, and G-CSF)-based chemotherapy, and serum SDF-1α levels were assessed using ELISA. Serum SDF-1α levels were significantly elevated in elderly AML patients compared to controls (p < 0.001). Receiver operating characteristic (ROC) analysis confirmed its diagnostic relevance, revealing the area under the ROC curve (AUC) of 0.76. Factors such as age, French-American-British (FAB) classification, Eastern Cooperative Oncology Group (ECOG) performance status, primary AML status, white blood cell count, and bone marrow blast cell ratio, were confirmed to be prognostically relevant. Serum SDF-1α levels were elevated in patients who did not achieve complete remission (NCR) compared to those in complete remission (CR). ROC analysis further highlighted the predictive capability of serum SDF-1α for chemotherapy responsiveness. Independent predictors of treatment failure included age, FAB classification, ECOG status, and serum SDF-1α levels. Following chemotherapy, serum SDF-1α levels decreased in patients in CR but remained unchanged in those in NCR. Higher baseline levels of SDF-1α were associated with shorter overall survival. Elevated serum SDF-1α levels in elderly AML patients are associated with poor chemotherapy response and shorter survival. Baseline serum SDF-1α levels could serve as a prognostic marker for CAG-based treatment outcomes.

Elevated levels of plasma inactive stromal cell derived factor-1a predict long-term adverse outcomes in diabetic patients with coronary artery disease

Abstract Background Because of the significantly increased cardiovascular risk by complicating type 2 diabetes (T2D) in patients with coronary artery disease (CAD), the appropriate risk estimation is crucial in patients with T2D following percutaneous coronary intervention (PCI). Nevertheless, there is no established biomarker which can precisely predict outcomes in this particular population. Although stromal cell derived factor-1α (SDF-1α) has been suggested to play a key role in the pathogenesis of T2D, the prognostic impact of SDF-1α in the secondary prevention of CAD is yet to be elucidated. In particular, the ability of SDF-1α isoforms in outcome prediction in this population has not been assessed. Purpose The aim of present study was to investigate the prognostic implication of three isoforms of SDF-1α, such as total, active, and inactive forms of SDF-1α in diabetic patients following PCI. Methods This single-center retrospective analysis involved consecutive patients with T2D who underwent PCI for the first time between 2008 and 2018 (n=849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. Participants were divided into two groups according to the median of three forms of plasma SDF-1α levels (total SDF-1α: 2270 pg/mL, active SDF-1α: 686 pg/mL, inactive SDF-1α: 1537 pg/mL) at PCI procedure and the incidence and risk of subsequent endpoints following PCI were assessed. Results Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α (Figure 1). Constantly, multivariate Cox hazard analyses adjusted by age, sex, body mass index (&amp;gt;25), acute coronary syndrome, and chronic kidney disease (≥ stage 3) repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.21, 95% confidence interval (CI): 1.05–4.67, p=0.04) and 3P-MACE (HR: 2.30, 95% CI: 1.01–5.09, p=0.04). However, neither of total and active SDF-1α reached statistical significance (Figure 2). Furthermore, the addition of inactive SDF-1α to baseline models in multivariate Cox proportional hazard analysis significantly enhanced both the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) for all-cause death (NRI 0.29, p=0.009; IDI 0.007, p=0.03) and 3P-MACE (NRI 0.38, p=0.001; IDI 0.007, p=0.01) while adding total and active SDF-1α did not improve them. Conclusion In diabetic patients following PCI, elevated levels of plasma inactive SDF-1α, not total and active isoforms, might be a useful indicator of adverse outcomes.

Comprehensive analysis of serum cytokines in patients with multiple myeloma before and after lenalidomide and dexamethasone.

Multiple myeloma (MM) is an incurable B-cell malignancy often accompanied by profound immunodeficiency. Lenalidomide (Len) is an immunomodulatory drug that exerts promising therapeutic effects on MM through the immune system. However, predictive markers related to the effects of Len treatment are not fully understood. This study aimed to identify candidate biomarkers for predicting the clinical efficacy of Len and dexamethasone (Ld) therapy through a comprehensive analysis of serum cytokines. The levels of 48 cytokines in the serum of patients with MM just before Ld therapy (n = 77), at the time of best response (n = 56), and at disease progression (n = 49) were measured and evaluated. Patients with high IL-18 and M-CSF levels showed significantly shorter progression-free survival and overall survival (OS). In contrast, patients with high PDGF-BB levels had longer survival. Moreover, low levels of G-CSF, IL-7, IL-8, and SDF-1α were associated with shorter OS after Ld therapy. During Ld therapy, pro-inflammatory cytokines such as IL-2Rα, IL-18, and TNF-α were decreased, while IFN-γ was increased. IL-4 and IL-6 levels increased during disease progression. In conclusion, this study provides a better understanding of the association between cytokines and the efficacy of Ld therapy as well as the unique changes in cytokines related to inflammatory and immune responses during Ld therapy.

Targeted mitigation of neointimal hyperplasia via magnetic field-directed localization of superparamagnetic iron oxide nanoparticle-labeled endothelial progenitor cells following carotid balloon catheter injury in rats

BackgroundThe transplantation of endothelial progenitor cells (EPCs) has been shown to reduce neointimal hyperplasia following arterial injury. However, the efficacy of this approach is hampered by limited homing of EPCs to the injury site. Additionally, the in vivo recruitment and metabolic activity of transplanted EPCs have not been continuously monitored. MethodsEPCs were labeled with indocyanine green (ICG)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) and subjected to external magnetic field targeting to enhance their delivery to a carotid balloon injury (BI) model in Sprague–Dawley rats. Magnetic particle imaging (MPI)/ fluorescence imaging (FLI) multimodal in vivo imaging, 3D MPI/CT imaging and MPI/FLI ex vivo imaging was performed after injury. Carotid arteries were collected and analyzed for pathology and immunofluorescence staining. The paracrine effects were analyzed by enzyme-linked immunosorbent assay. ResultsThe application of a magnetic field significantly enhanced the localization and retention of SPIONs@PEG-ICG-EPCs at the site of arterial injury, as evidenced by both in vivo continuous monitoring and ex vivo by observation. This targeted delivery approach effectively inhibited neointimal hyperplasia and increased the presence of CD31-positive cells at the injury site. Moreover, serum levels of SDF-1α, VEGF, IGF-1, and TGF-β1 were significantly elevated, indicating enhanced paracrine activity. ConclusionsOur findings demonstrate that external magnetic field-directed delivery of SPIONs@PEG-ICG-EPCs to areas of arterial injury can significantly enhance their therapeutic efficacy. This enhancement is likely mediated through increased paracrine signaling. These results underscore the potential of magnetically guided SPIONs@PEG-ICG-EPCs delivery as a promising strategy for treating arterial injuries.

Peripheral inflammatory response in people after acute ischaemic stroke and isolated spontaneous cervical artery dissection.

The systemic inflammatory response following acute ischaemic stroke remains incompletely understood. We characterised the circulating inflammatory profile in 173 acute ischaemic stroke patients by measuring 65 cytokines and chemokines in plasma. Participants were grouped based on their inflammatory response, determined by high-sensitivity C-reactive protein levels in the acute phase. We compared stroke patients' profiles with 42 people experiencing spontaneous cervical artery dissection without stroke. Furthermore, variations in cytokine levels among stroke aetiologies were analysed. Follow-up samples were collected in a subgroup of ischaemic stroke patients at three and twelve months. Ischaemic stroke patients had elevated plasma levels of HGF and SDF-1α, and lower IL-4 levels, compared to spontaneous cervical artery dissection patients without stroke. Aetiology-subgroup analysis revealed reduced levels of nine cytokines/chemokines (HGF, SDF-1α, IL-2R, CD30, TNF-RII, IL-16, MIF, APRIL, SCF), and elevated levels of IL-4 and MIP-1β, in spontaneous cervical artery dissection (with or without ischaemic stroke as levels were comparable between both groups) compared to other aetiologies. The majority of cytokine/chemokine levels remained stable across the study period. Our research indicates that stroke due to large artery atherosclerosis, cardioembolism, and small vessel occlusion triggers a stronger inflammatory response than spontaneous cervical artery dissection.

Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention

BackgroundSince the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI.MethodsThis single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α.ResultsUnadjusted Kaplan–Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28–5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12–5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively).ConclusionThe study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI.Trial registration: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan—Clinical Trials Registry, UMIN-CTR 000035587).

Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α.

Pancreatic β-cell failure is a pathological feature in type 1 diabetes. One promising approach involves inducing transdifferentiation of related pancreatic cell types, specifically α cells that produce glucagon. The chemokine stromal cell-derived factor-1 alpha (SDF-1α) is implicated in pancreatic α-to-β like cell transition. Here, the serum level of SDF-1α was lower in T1D with C-peptide loss, the miR-23a was negatively correlated with SDF-1α. We discovered that exosomal miR-23a, secreted from β cells, functionally downregulates the expression of SDF-1α, leading to increased Pax4 expression and decreased Arx expression in vivo. Adenovirus-vectored miR-23a sponge and mimic were constructed to further explored the miR-23a on pancreatic α-to-β like cell transition in vitro, which yielded results consistent with our cell-based assays. Suppression of miR-23a upregulated insulin level and downregulated glucagon level in STZ-induced diabetes mice models, effectively promoting α-to-β like cell transition. Our findings highlight miR-23a as a new therapeutic target for regenerating pancreatic β cells from α cells.

Distinct patterns of cytokines, chemokines, and growth factors in synovial fluid after ACL injury in comparison to osteoarthritis.

This study analyzed knee synovial fluid after anterior cruciate ligament (ACL) tear and in osteoarthritis (OA) to test the hypotheses that concentrations of cytokines, chemokines, and growth factors differ (a) by diagnosis and (b) after ACL tear by time from injury and presence/absence of concomitant meniscus tear. Synovial fluid samples were collected from two groups, ACL tears (with or without meniscus tear) (N = 13) and Kellgren-Lawrence grade 3 and 4 OA (N = 16), undergoing clinically indicated aspiration of the knee joint. Multiple cytokines, chemokines, and growth factors were assessed using a multiplexed 45-protein panel. Comparisons were made for the concentrations of all molecules between ACL tear and OA patients, isolated versus combined ACL and meniscus tears, and categorized by time from injury: acute or early subacute (<15 days, N = 8) versus late subacute or chronic (>15 days and <3 months, N = 5). ACL tear patients have higher levels of six molecules (IL-4, IL-5, IL-13, PlGF-1, bNGF, TNF-α) in knee synovial fluid compared to OA patients. Isolated ACL tears express higher levels of IL-4, IL-13 and IFN-γ and lower levels of IL-7 than ACL tears with a concomitant meniscus tear. SDF-1α, PlGF-1, IL-1RA, HGF, bNGF, and BDNF levels are elevated immediately after injury and drop off significantly in the late subacute phase (after 15 days). Synovial fluid from knees with ACL tears have elevated metabolic activity compared to knees with OA. The cytokine profiles after ACL tears are influenced by the time from injury and the presence of meniscus tears. These findings offer valuable insights into the levels of cytokines, chemokines, and growth factors in the knee after ACL injury, information which may have important implications for the diagnosis, prognosis and treatment of this common pathology.

Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment

BackgroundPolycystic ovary syndrome (PCOS) is the main cause of anovulatory infertility in women of reproductive age, and low-grade chronic inflammation plays a key role in the occurrence and development of PCOS. However, obesity, as a likely confounding factor, can affect the inflammatory state of PCOS patients.ObjectiveThe aim of this study was to comprehensively investigate intra-ovarian inflammatory states and their impact on embryo quality in PCOS patients with a normal BMI undergoing IVF treatment.MethodsDIA-mass spectrometry-based proteomics and bioinformatic analysis were combined to comprehensively profile the protein expression of granulosa cells (GCs) from 5 normal-BMI PCOS patients and 5 controls. Thirty-four cytokines were further systematically detected in follicular fluid (FF) from 32 age- and BMI-matched normal-BMI patients using Luminex liquid chip suspension technology. Next, the differentially expressed cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA) in 24 newly recruited subjects, and the relationship between these cytokines and embryo quality in PCOS patients was analysed. Finally, these cytokine levels were compared and evaluated in PCOS patients with different androgen levels.ResultsProteomic analysis showed that the suppression of substance metabolism and steroid biosynthesis, more interestingly, resulted in an enhanced immune and inflammatory response in the GCs of normal-BMI PCOS patients and prompted the involvement of cytokines in this process. Luminex analysis further showed that FF macrophage inflammatory protein-1 beta (MIP-1β) and stromal cell-derived factor-1 alpha (SDF-1α) levels were significantly increased in normal-BMI PCOS patients compared to controls (P = 0.005; P = 0.035, respectively), and the ELISA results were consistent with these findings. Besides, FF MIP-1β showed an inverse correlation with the number of D3 good-quality embryos and the good-quality blastocyst rate in patients with PCOS (P = 0.006; P = 0.003, respectively), which remained significant after correction for multiple comparisons. Moreover, SDF-1α levels had no relationship with embryo development in PCOS patients. Additionally, SDF-1α levels were significantly lower in PCOS patients with high androgen levels than in controls (P = 0.031).ConclusionsLocal ovarian inflammation was present in normal-BMI PCOS patients, affecting follicular development, and FF MIP-1β may be a potential biomarker associated with embryo quality in normal-BMI PCOS patients.Graphical abstract

FGF2/HGF priming facilitates adipose-derived stem cell-mediated bone formation in osteoporotic defects

AimsThe activity of adipose-derived stem cells (ADSCs) is susceptible to the physiological conditions of the donor. Therefore, employing ADSCs from donors of advanced age or with diseases for cell therapy necessitates a strategy to enhance therapeutic efficacy before transplantation. This study aims to investigate the impact of supplementing Fibroblast Growth Factor 2 (FGF2) and Hepatocyte Growth Factor (HGF) on ADSC-mediated osteogenesis under osteoporotic conditions and to explore the underlying mechanisms of action. Main methodsAdipose-derived stem cells (ADSCs) obtained from ovariectomized (OVX) rats were cultured ex vivo. These cells were cultured in an osteogenic medium supplemented with FGF2 and HGF and subsequently autologously transplanted into osteoporotic femur defects using Hydroxyapatite-Tricalcium Phosphate. The assessment of bone formation was conducted four weeks post-transplantation. Key findingsOsteoporosis detrimentally affects the viability and osteogenic differentiation potential of ADSCs, often accompanied by a deficiency in FGF2 and HGF signaling. However, priming with FGF2 and HGF facilitated the formation of immature osteoblasts from OVX ADSCs in vitro, promoting the expression of osteoblastogenic proteins, including Runx-2, osterix, and ALP, during the early phase of osteogenesis. Furthermore, FGF2/HGF priming augmented the levels of VEGF and SDF-1α in the microenvironment of OVX ADSCs under osteogenic induction. Importantly, transplantation of OVX ADSCs primed with FGF2/HGF for 6 days significantly enhanced bone formation compared to non-primed cells. The success of bone regeneration was confirmed by the expression of type-1 collagen and osteocalcin in the bone tissue of the deficient area. SignificanceOur findings corroborate that priming with FGF2/HGF can improve the differentiation potential of ADSCs. This could be applied in autologous stem cell therapy for skeletal disease in the geriatric population.

Vagus nerve stimulation-induced stromal cell-derived factor-l alpha participates in angiogenesis and repair of infarcted hearts.

We aim to explore the role and mechanism of vagus nerve stimulation (VNS) in coronary endothelial cells and angiogenesis in infarcted hearts. Seven days after rat myocardial infarction (MI) was prepared by ligation of the left anterior descending coronary artery, the left cervical vagus nerve was treated with electrical stimulation 1h after intraperitoneal administration of the α7-nicotinic acetylcholine inhibitor mecamylamine or the mAChR inhibitor atropine or 3days after local injection of Ad-shSDF-1α into the infarcted heart. Cardiac tissue acetylcholine (ACh) and serum ACh, tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels were detected by ELISA to determine whether VNS was successful. An inflammatory injury model in human coronary artery endothelial cells (HCAECs) was established by lipopolysaccharide and identified by evaluating TNF-α, IL-1β and IL-6 levels and tube formation. Immunohistochemistry staining was performed to evaluate CD31-positive vessel density and stromal cell-derived factor-l alpha (SDF-1α) expression in the MI heart in vivo and the expression and distribution of SDF-1α, C-X-C motif chemokine receptor 4 and CXCR7 in HCAECs in vitro. Western blotting was used to detect the levels of SDF-1α, V-akt murine thymoma viral oncogene homolog (AKT), phosphorylated AKT (pAKT), specificity protein 1 (Sp1) and phosphorylation of Sp1 in HCAECs. Left ventricular performance, including left ventricular systolic pressure, left ventricular end-diastolic pressure and rate of the rise and fall of ventricular pressure, should be evaluated 28days after VNS treatment. VNS was successfully established for MI therapy with decreases in serum TNF-α, IL-1β and IL-6 levels and increases in cardiac tissue and serum ACh levels, leading to increased SDF-1α expression in coronary endothelial cells of MI hearts, triggering angiogenesis of MI hearts with increased CD31-positive vessel density, which was abolished by the m/nAChR inhibitors mecamylamine and atropine or knockdown of SDF-1α by shRNA. ACh promoted SDF-1α expression and its distribution along with the branch of the formed tube in HCAECs, resulting in an increase in the number of tubes formed in HCAECs. ACh increased the levels of pAKT and phosphorylation of Sp1 in HCAECs, resulting in inducing SDF-1α expression, and the specific effects could be abolished by mecamylamine, atropine, the PI3K/AKT blocker wortmannin or the Sp1 blocker mithramycin. Functionally, VNS improved left ventricular performance, which could be abolished by Ad-shSDF-1α. VNS promoted angiogenesis to repair the infarcted heart by inducing SDF-1α expression and redistribution along new branches during angiogenesis, which was associated with the m/nAChR-AKT-Sp1 signalling pathway.

Exploration of the influence of early rehabilitation training on circulating endothelial progenitor cell mobilization in patients with acute ischemic stroke and its related mechanism under a lightweight artificial intelligence algorithm.

This work aimed to explore the application of lightweight artificial intelligence algorithms in magnetic resonance imaging (MRI) image processing of patients with acute ischemic stroke (AIS) to clarify the effect and mechanism of early rehabilitation training on the mobilization of circulating endothelial progenitor cells (EPCs) in AIS. A total of 98 AIS patients undergoing MRI examination were selected as the research objects and were randomly divided into a rehabilitation group (early rehabilitation training, 50 cases) and a routine group (conventional treatment, 48 cases) by random number table method and lottery method. In this work, based on the convolutional neural network (CNN) algorithm, a low-rank decomposition algorithm was introduced to optimize it, and a lightweight MRI image computer intelligent segmentation model (LT-RCNN) was established. The LT-RCNN model was used in the MRI image processing of AIS patients, and the role of the model in AIS image segmentation and lesion localization was analyzed. Furthermore, flow cytometry was used to detect the number of peripheral circulating EPCs and CD34+KDR+ cells in the two groups of patients before and after treatment. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin 10 (IL-10), and stromal cell-derived factor-1α (SDF-1α) content were detected by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, the correlation between each factor and CD34+KDR+ was analyzed by Pearson linear correlation. The diffusion-weighted imaging (DWI) signal of MRI images of AIS patients under the LT-RCNN model was high. The location of the lesion could be accurately detected, and the contour of the lesion could be displayed and segmented, and the segmentation accuracy and sensitivity were significantly better than before optimization. The number of EPCs and CD34+KDR+ cells in the rehabilitation group was increased compared with the control group (p<0.01); the expression levels of VEGF, IL-10, and SDF-1α were higher than those of the control group (p<0.001), and TNF-α content was lower than the control group (p<0.001). The number of CD34+KDR+ cells was positively correlated with VEGF, IL-10, and TNF-α contents (p<0.01). The results showed that the computer-intelligent segmentation model LT-RCNN could accurately locate, and segment AIS lesions and the early rehabilitation training could change the expression level of inflammatory factors and further promote the mobilization of AIS circulation EPCs.

PORTO-001 study: Changes in the oral microbiome and matrix metalloproteinases in patients with oropharyngeal squamous cell carcinoma undergoing definitive chemoradiotherapy.

e18034 Background: Head and neck cancer patients treated with concurrent chemoradiotherapy (CRT) develop oral mucositis, with varying severity. However, knowledge about risk factors, biomarkers, treatment, and prognosis of oral mucositis is still limited. Methods: We designed an exploratory study to examine the changes in the oral microbiome and salivary and plasma levels of matrix metalloproteinases (MMP) in patients with locoregionally advanced oropharyngeal squamous cell carcinoma (OPSCC) undergoing definitive CRT. Patients were followed from screening to week 7 of treatment with CRT, which consisted of 70 Gy/35 fractions of radiation with cisplatin given at 100 mg/m2 q3weeks or weekly 40 mg/m2. Clinical and demographic data were collected at specified timepoints. Samples were collected at screening and on week 4 of treatment with CRT. A tumor swab was collected for microbiome analysis. Blood and saliva samples were collected for measurements of 7 MMPs and 26 other cytokines. The study population was summarized descriptively. The change in the cytokines and the α-diversity of microbiome data (week 4 vs screening) were examined using Wilcoxon signed rank test. Results: A total of 11 patients were included. Nine (82%) were male. 5 patients (45%) were stage III, and there were 2 patients (18%) for each of stages I, II, and IV. A history of smoking was present in 5 (45.4%) patients. p16 was positive in 9 (81.8%) patients. There was a median weight loss of 7.0% (5.1 kg) between screening and week 7 visits. Almost half (45%) of patients developed grade 2 oral mucositis. All patients developed radiation dermatitis, with most cases ranging between grades 2 and 3. There were no statistically significant changes in the salivary levels of cytokines. However, 1 patient developed clinical oral mucositis before all the other patients, at week 1, and this was associated with an upsurge in the salivary levels of IFN-γ, IL-6, TNF-α, MMP-1, MMP-2 and MMP-7. For all patients, there were statistically significant changes (median (95% confidence interval)) in the blood plasma levels of IP-10 (-0.1 fluorescence intensity (FI) (-0.3, -0.04), p = 0.01), MIP-1ß (0.2 FI (0.07, 0.5), p = 0.02), SDF-1α (1.4 pg/ml (0.07, 3.7), p = 0.02), MMP-1 (-0.4 pg/ml (-0.5, -0.09), p = 0.01), MMP-3 (0.4 pg/ml (0.03, 0.5), p = 0.02), and MMP-8 (-0.2 FI (-0.3, -0.02), p = 0.04). There was a 29.1% ((-3.0%, -32.8%), p = 0.005) reduction in α-diversity of microbiome at week 4 from screening. Conclusions: In this small series of patients diagnosed with OPSCC, there was a change in the plasma levels of IP-10, MIP-1ß, SDF-1α, MMP-1, MMP-3, and MMP-8, as well as a reduction in the α-diversity of the oral microbiome. Larger studies are needed to confirm these results. If confirmed, these changes might imply a potential role as predictive or pharmacodynamic biomarkers for oral mucositis.

SDF-1α promotes subchondral bone sclerosis and aggravates osteoarthritis by regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

BackgroundSubchondral bone sclerosis is a major feature of osteoarthritis (OA), and bone marrow mesenchymal stem cells (BMSCs) are presumed to play an important role in subchondral bone sclerosis. Accumulating evidence has shown that stromal cell-derived factor-1α (SDF-1α) plays a key role in bone metabolism-related diseases, but its role in OA pathogenesis remains largely unknown. The purpose of this study was to explore the role of SDF-1α expressed on BMSCs in subchondral bone sclerosis in an OA model.MethodsIn the present study, C57BL/6J mice were divided into the following three groups: the sham control, destabilization of the medial meniscus (DMM), and AMD3100-treated DMM (DMM + AMD3100) groups. The mice were sacrificed after 2 or 8 weeks, and samples were collected for histological and immunohistochemical analyses. OA severity was assessed by performing hematoxylin and eosin (HE) and safranin O-fast green staining. SDF-1α expression in the OA model was measured using an enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (q-PCR), and immunohistochemistry. Micro-CT was used to observe changes in subchondral bone in the OA model. CD44, CD90, RUNX2, and OCN expression in subchondral bone were measured using q-PCR and immunohistochemistry. In vitro, BMSCs were transfected with a recombinant lentivirus expressing SDF-1α, an empty vector (EV), or siRNA-SDF-1α. Western blot analysis, q-PCR, and immunofluorescence staining were used to confirm the successful transfection of BMSCs. The effect of SDF-1α on BMSC proliferation was evaluated by performing a CCK-8 assay and cell cycle analysis. The effect of SDF-1α on the osteogenic differentiation of BMSCs was assessed by performing alkaline phosphatase (ALP) and alizarin red S (ARS) staining. Cyclin D1, RUNX2 and OCN expression were measured using Western blot analysis, q-PCR, and immunofluorescence staining.ResultsSDF-1α expression in the DMM-induced OA model increased. In the DMM + AMD3100 group, subchondral bone sclerosis was alleviated, OA was effectively relieved, and CD44, CD90, RUNX2, and OCN expression in subchondral bone was decreased. In vitro, high levels of SDF-1α promoted BMSC proliferation and increased osteogenic differentiation. Cyclin D1, RUNX2, and OCN expression increased.ConclusionThe results of this study reveal a new molecular mechanism underlying the pathogenesis of OA. The targeted regulation of SDF-1α may be clinically effective in suppressing OA progression.

Reduced homovanillic acid, SDF-1α and SCGF-β levels in cerebrospinal fluid are related to depressive states in systemic lupus erythematosus.

This study aimed to seek a new method of evaluation and surrogate markers for diffuse neuropsychiatric SLE (NPSLE). We enrolled 44 patients with SLE between 2017 and 2020 who fulfilled at least one of three specific inclusion criteria: high disease activity, abnormal findings (cerebrospinal fluid [CSF] examination, brain MRI, or electroencephalography), or history of neuropsychiatric illness. Psychiatric symptom rating scales (PSYRATS) were evaluated retrospectively. The primary end point was the PSYRATS positivity rate in SLE patients who had not been diagnosed with diffuse NPSLE. Based on the 1999 ACR classifications, 7 out of the 44 patients evaluated using PSYRATS had been diagnosed with diffuse NPSLE. PSYRATS positivity was seen in 13 out of 37 SLE patients (35.1%) who had not been diagnosed with diffuse NPSLE, and all these patients were positive for Montgomery-Åsberg Depression Rating Scale (MADRS), an indicator of depression state in PSYRATS. Additionally, in the 20 SLE patients exhibiting depression symptoms who were MADRS-positive, CSF concentrations of the neuroinflammatory markers homovanillic acid (HVA; P = 0.0400), stromal cell-derived factor-1α (SDF-1α; P = 0.0431) and stem cell growth factor-β (SCGF-1β; P = 0.0061) were significantly reduced compared with the 24 MADRS-negative SLE patients, and the levels of HVA, SDF-1α and SCGF-1β correlated with one another (P < 0.05). Many patients with active SLE have subclinical depression, and MADRS evaluation of neuropsychiatric symptoms is useful for detecting them. Additionally, the decrease in CSF levels of HVA, SDF-1 α and SCGF-1β reflects the same pathology, and these may serve as surrogate markers.

The stereological, immunohistological, and gene expression studies in an infected ischemic wound in diabetic rats treated by human adipose-derived stem cells and photobiomodulation.

We investigated the impacts of photobiomodulation (PBM) and human allogeneic adipose-derived stem cells (ha-ADS) together and or alone applications on the stereological parameters, immunohistochemical characterizing of M1 and M2 macrophages, and mRNA levels of hypoxia-inducible factor (HIF-1α), basic fibroblast growth factor (bFGF), vascular endothelial growth factor-A (VEGF-A) and stromal cell-derived factor-1α (SDF-1α) on inflammation (day 4) and proliferation phases (day 8) of repairing tissues in an infected delayed healing and ischemic wound model (IDHIWM) in type 1 diabetic (DM1) rats. DM1 was created in 48 rats and an IDHIWM was made in all of them, and they were distributed into 4 groups. Group1 = control rats with no treatment. Group2 = rats received (10 × 100000ha-ADS). Group3 = rats exposed to PBM (890nm, 80Hz, 3.46J/cm2). Group4 = rats received both PBM and ha-ADS. On day 8, there were significantly higher neutrophils in the control group than in other groups (p < 0.01). There were substantially higher macrophages in the PBM + ha-ADS group than in other groups on days 4 and 8 (p < 0.001). Granulation tissue volume, on both days 4 and 8, was meaningfully greater in all treatment groups than in the control group (all, p = 0.000). Results of M1 and M2 macrophage counts of repairing tissue in the entiretreatmentgroups were considered preferable to those in the control group (p < 0.05). Regarding stereological and macrophage phenotyping, the results of the PBM + ha-ADS group were better than the ha-ADS and PBM groups. Results of the tested gene expression of repairing tissue on inflammation and proliferation steps in PBM and PBM + ha-ADS groups were meaningfully better than the control and ha-ADS groups (p < 0.05). We showed that PBM, ha-ADS, and PBM plus ha-ADS, hastened the proliferation step of healing in an IDHIWM in rats with DM1 by regulation of the inflammatory reaction, macrophage phenotyping, and augmented granulation tissue formation. In addition PBM and PBM plus ha-ADS protocols hastened and increased mRNA levels of HIF-1α, bFGF, SDF-1α, and VEGF-A. Totally, in terms of stereological and immuno-histological tests, and also gene expression HIF-1α and VEGF-A, the results of PBM + ha-ADS were superior (additive) to PBM, and ha-ADS alone treatments.

Bone Marrow Adipocytes Promote the Survival of Multiple Myeloma Cells and Up-Regulate Their Chemoresistance

To investigate the effect of adipocytes in the bone marrow microenvironment of patients with multiple myeloma (MM) on the pathogenesis of MM. Bone marrow adipocytes (BMA) in bone marrow smears of health donors (HD) and newly diagnosed MM (ND-MM) patients were evaluated with oil red O staining. The mesenchymal stem cells (MSC) from HD and ND-MM patients were isolated, and in vitro co-culture assay was used to explore the effects of MM cells on the adipogenic differentiation of MSC and the role of BMA in the survival and drug resistance of MM cells. The expression of adipogenic/osteogenic differentiation-related genes PPAR-γ, DLK1, DGAT1, FABP4, FASN and ALP both in MSC and MSC-derived adipocytes was determined with real-time quantitative PCR. The Western blot was employed to detect the expression levels of IL-6, IL-10, SDF-1α, TNF-α and IGF-1 in the supernatant with or without PPAR-γ inhibitor. The results of oil red O staining of bone marrow smears showed that BMA increased significantly in patients of ND-MM compared with the normal control group, and the BMA content was related to the disease status. The content of BMA decreased in the patients with effective chemotherapy. MM cells up-regulated the expression of MSC adipogenic differentiation-related genes PPAR-γ, DLK1, DGAT1, FABP4 and FASN, but the expression of osteogenic differentiation-related gene ALP was significantly down-regulated. This means that the direct consequence of the interaction between MM cells and MSC in the bone marrow microenvironment is to promote the differentiation of MSC into adipocytes at the expense of osteoblasts, and the cytokines detected in supernatant changed. PPAR-γ inhibitor G3335 could partially reverse the release of cytokines by BMA. Those results confirmed that BMA regulated the release of cytokines via PPAR-γ signal, and PPAR-γ inhibitor G3335 could distort PPAR-γ mediated BMA maturation and cytokines release. The increased BMA and related cytokines effectively promoted the proliferation, migration and drug resistance of MM cells. The BMA and its associated cytokines are the promoting factors in the survival, proliferation and migration of MM cells. BMA can protect MM cells from drug-induced apoptosis and plays an important role in MM treatment failure and disease progression.

Megrment the Level of SDF1-Α in the Serum of Patients with Urinary Tract Infection and Patients with Vaginal Infection

Urinary tract infection, Bacterial vaginosis as one of the global threats affecting millions of women and causing some time deaths around the world. Objective: This study aims to assess levels of SDF1 and IgA in patients with Urinary tract infection, Bacterial vaginosis, and people enjoying good health as a control group. Methods: Collecting medical information from (180) participants in the Imam Al-Sadiq General Teaching Hospital in Iraq-Babylon, the Gynecology Consultant, according to specific criteria, the subjects were divided into three groups: the control group, the patients (UTI, BV), while the demographic study included age, education, Jobs, and living Laboratory results, signs and symptoms, SDF1-α and IgA levels were assessed by the enzyme-linked immunosorbent assay (ELISA) technique. Results: The results revealed that there were significant variations in SDF1 and IgA between the UTI group, BV group, and control groups. SDF1 level with the UTI group was (1.206522 ±.0927277 pg/ml) and for patients with BV was(1.213735 ±.0661389 pg/ml) whereas the control group appear was (1.130013±.0496400 pg/ml), IgA level in the UTI patients was (64.252983 ± 7.5946759pg/ml) and patients with BV was (60.441928±6.1457661pg/ml) whereas the control group appears was (48.011745 ±4.7938613 pg/ml) Conclusion: They can be considered good indicators to give knowledge about the diagnosis of urinary tract infection and bacterial vaginosis, and help doctors to give appropriate medications. Keywords: Urinary tract infection, bacterial vaginosis, stromal cell-derived factor 1-alpha, Immunoglobulin A.

SDF-1α-Releasing Microspheres Effectively Extend Stem Cell Homing after Myocardial Infarction

Ischemic heart disease (IHD) is one of the main focuses in today's healthcare due to its implications and complications, and it is predicted to be increasing in prevalence due to the ageing population. Although the conventional pharmacological and interventional methods for the treatment of IHD presents with success in the clinical setting, the long-term complications of cardiac insufficiency are on a continual incline as a result of post-infarction remodeling of the cardiac tissue. The migration and involvement of stem cells to the cardiac muscle, followed by differentiation into cardiac myocytes, has been proven to be the natural process, though at a slow rate. SDF-1α is a novel candidate to mobilize stem cells homing to the ischemic heart. Endogenous SDF-1α levels are elevated after myocardial infarction, but their presence gradually decreases after approximately seven days. Additional administration of SDF-1α-releasing microspheres could be a tool for the extension of the time the stem cells are in the cardiac tissue after myocardial infarction. This, in turn, could constitute a novel therapy for more efficient regeneration of the heart muscle after injury. Through this practical study, it has been shown that the controlled release of SDF-1α from biodegradable microspheres into the pericardial sac fourteen days after myocardial infarction increases the concentration of exogenous SDF-1α, which persists in the tissue much longer than the level of endogenous SDF-1α. In addition, administration of SDF-1α-releasing microspheres increased the expression of the factors potentially involved in the involvement and retention of myocardial stem cells, which constitutes vascular endothelial growth factor A (VEGFA), stem cell factor (SCF), and vascular cell adhesion molecules (VCAMs) at the site of damaged tissue. This exhibits the possibility of combating the basic limitations of cell therapy, including ineffective stem cell implantation and the ability to induce the migration of endogenous stem cells to the ischemic cardiac tissue and promote heart repair.