Stromal Cell-derived Factor-1 Levels Research Articles

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.

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.

Saxagliptin alleviates erectile dysfunction through increasing stromal cell-derived factor-1 in diabetes mellitus.

Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED. To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED. The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into three groups (n=8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection. We found that erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100. Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4 is may be beneficial to the management of DMED.

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

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

The role of Stromal Cell-Derived Factor 1 (SDF-1) and Transforming Growth-Factor-Beta 1 (TGF-?1) levels in Packed Red Cells (PRC) as the indicator of storage lesion at Sanglah Hospital-Blood Bank, Bali, Indonesia

Background: Packed Red Cells (PRC) is one of the blood component obtained from the whole blood through the removal of blood plasma. The storage of PRC aims to maintain the viability and function of erythrocytes by reducing cell metabolic activity. However, PRC's biochemistry changes could occur through storage lesion by releasing Stromal Cell-Derived Factor 1 (SDF-1) and Transforming Growth Factor-Beta 1 (TGF-?1) that affect the erythrocytes metabolism and viability prior to transfusion. This study aims to evaluate the increase of SDF-1 and TGF-?1 levels in PRC as the indicator of storage lesion at Sanglah Hospital-Blood Bank, Bali, Indonesia.Methods: An observational cross-sectional study using randomized post-test only without control group design was conducted at Sanglah Hospital-Blood Bank, Bali. The consecutive random sampling technique was used in this study to the PRC, who met the inclusion criteria. Samples of the SDF-1 group (N=84) were divided into 3 such as Group 1 (1-7 days), Group 2 (8-14 days), and Group 3 (15-21 days). However, 53 PRC was divided into 2 groups as Group 1 (1-7 days) and Group 2 (8-14 days). The SDF-1 and TGF-?1 levels were evaluated for each group using Human SDF-1/CXCL12 and TGF-?1 Kit from Elabcience® by ELISA method. Data were analyzed using SPSS version 25 for Windows software.Results: The median levels of SDF-1 in Group 1 group was 0.385 (0.050-1.020) ng/mL, followed by 0.455 (0.330-0.750) ng/ml in Group 2, and 0.490 (0.380-0.920) ng/ml in Group 3 (p&lt;0.05). The mean of TGF-?1 levels was slightly higher in Group 1 (2,365.21±715.96 pg/ml) compared with Group 2 (2,210.39±994.68 pg/ml) (p=0.523). There was a significant difference in SDF-1 levels in Group 1-Group 2 (P=0.041) and Group 1-Group 3 (P=0.000) groups; however, no significant difference was found in Group 2-Group 3 (P=0.133) using the Mann-Whitney test. The Spearman's rho test found a moderate positive correlation between SDF-1 levels and storage time by day (r=0.546; P=0.000). In addition, based on the Pearson correlation test, there was a weak positive correlation between TGF-?1 levels and storage time by day (r=0.461; p=0.001).Conclusion: The increase of SDF-1 and TGF-?1 levels in PRC by days of storage time could be used as the indicator for storage lesion at Sanglah General Hospital-Blood Bank, Bali, Indonesia.

Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig

BackgroundVarieties of animals were used to study osteoarthritis pathogenesis. The Diannan small-ear pig, which is native to Yunnan, China, is thought to have an articular anatomy similar to that of humans and is more likely to be a source of pathological tissues than other animals. The aim of this study was to determine whether this animal can serve as a more effective osteoarthritis model and explore the role of SDF-1/CXCR4 signaling pathway in the development of Osteoarthritis in animals.MethodsTwenty-seven adult pigs were randomly divided into three groups and underwent the Hulth procedure, papain articular injection, and conventional breeding. After 4, 8, and 12 weeks, cartilage tissues from knee joint were extracted for general and histological observation, immunofluorescence, and biochemical analysis. Synovium was taken out for stromal cell-derived factor-1 analysis.ResultsHistopathological observation showed obvious cartilage loss in two experimental groups, this cartilage loss was more severe in the chemical groups. Synovial stromal cell-derived factor1 levels increased over time in all groups. mRNA and protein levels of matrix metalloproteinase-3 were much higher in the chemical groups than in the other groups, whereas levels of collagen type II and aggrecan were significantly lower in the chemical groups than in the other groups. Immunofluorescence assays of collagen type II revealed an apparent reduction in this marker in the chemical groups compared with the other groups.ConclusionsThese results indicated that the Diannan small-ear pig can be used as an effective osteoarthritis model. In addition, it is much more convenient and much faster to induce osteoarthritis by intra-articular injection of papain, which is a method worthy of being promoted.

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

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

Therapeutic potential of mesenchymal stem cells for peripheral artery disease in a rat model of hindlimb ischemia.

Objective(s):Mesenchymal stem cells are viewed as the first choice in regenerative medicine. This study aimed to elucidate the influence of BM-MSCs transplantation on angiogenesis in a rat model of unilateral peripheral vascular disease. Materials and Methods:Twenty-one rats were arbitrarily allocated into three groups (7/group). Group I: control sham-operated rats, Group II: control ischemic group: Rats were subjected to unilateral surgical ligation of the femoral artery, and Group III: ischemia group: Rats were induced as in group II, 24 hr after ligation, they were intramuscularly injected with BM-MSCs. After scarification, gastrocnemius muscle gene expression of stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor receptor 2 (VEGFR2), von Willebrand factor (vWF), and hypoxia-inducible factor-1α (HIF-1α) were analyzed by quantitative real-time PCR. Muscle regeneration and angiogenesis evaluation was assessed through H&E staining of the tissue. Furthermore, Pax3 and Pax7 nuclear expression was immunohistochemically assessed. Results:Rats treated with BM-MSCs showed significantly raised gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF compared with control and ischemia groups. H&E staining of the gastrocnemius showed prominent new vessel formation. Granulation tissue within muscles of the ischemic treated group by BM-MSCs showed cells demonstrating nuclear expression of Pax3 and Pax7. Conclusion:BM-MSCs transplantation has an ameliorating effect on muscle ischemia through promoting angiogenesis, detected by normal muscle architecture restoration and new blood vessel formations observed by H&E, confirmed by increased gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF, decreased HIF-1α gene expression, and increased myogenic Pax7 gene expression.

Biochemical Characteristics and Clinical Result of Bone Marrow–Derived Fibrin Clot for Repair of Isolated Meniscal Injury in the Avascular Zone

To characterize bone marrow aspirate-derived fibrin clot (BMA clot) and evaluate the clinical result of meniscal repair with a BMA clot for isolated meniscal injury in the avascular zone. Blood counts of total leukocytes, platelets, and concentrations of basic fibroblast growth factor (bFGF), transforming growth factor β (TGF-β), and stromal cell-derived factor 1 (SDF-1) were analyzed with BMA, peripheral blood (PB), BMA clot, and PB clot from 5 patients treated for meniscal repair. In addition, a retrospective analysis of 30 patients with isolated avascular meniscal injuries who underwent repair with a BMA clot was performed to assess rate failure. Avascular meniscal injury was identified as horizontal tear, radial tear, and flap tear. Clinical failure was defined as the presence of 1 or more of Barrett's criteria. Anatomic failure was defined as the existence of equivalent signal intensity to intra-articular fluid along the repair area on follow-up magnetic resonance imaging (MRI). Patients' demographic and clinical data were compared between the overall failure group and the success group. The bFGF, TGF-β, and SDF-1 levels of BMA clots were more highly concentrated compared with PB clots. The Lysholm scores and meniscal status evaluated by MRI were significantly improved from preoperatively to postoperatively (both P < .001). The Kellgren-Lawrence grading of knee radiographs did not significantly differ pre- and postoperatively (P= .140). Rates of clinical failure, anatomic failure, and retear were 10%, 6.7%, and 3.3%, respectively. The demographic characteristics and surgical and postoperative status did not significantly differ between the overall failure group and the success group. BMA clots had increased levels of cytokines compared to PB clots. The retrospective analysis revealed that the rates of clinical failure and anatomic failure after meniscal repair with a BMA clot for isolated avascular meniscal injury were 10% and 6.7%, respectively. Level IV, case series.

Role of Interleukin‐17A in Contributing to the Central Inflammation in Rats with Heart Failure‐Induced by Myocardial Infarction

Inflammation and immune activation have been implicated in the progression of heart failure (HF). The cytokine interleukin (IL)-17A (commonly known as IL-17), is a key inflammatory regulator orchestrating immune responses to promote chronic inflammation. IL-17A has been identified as an important inflammatory mediator in the pathogenesis of several autoimmune diseases. However, emerging evidence indicated that IL-17A also contributes to the pathophysiology in cardiovascular diseases. We previously reported that peripherally administrated IL-17A acts within the brain to upregulate the expression of a variety of inflammatory cytokines and chemokines and dramatically increase hemodynamic responses and sympathetic outflow. The IL-17 receptor A (IL-17RA) is substantially expressed in the hypothalamic paraventricular nucleus (PVN), a key cardiovascular/autonomic brain center. The present study sought to determine whether IL-17A level is elevated in HF and, if so, whether increased IL-17A contributes to the central inflammation in this disease setting. Adult male Sprague Dawley rats were studied 4 weeks after coronary artery ligation to induce HF, or sham-operation (Sham). Myocardial infarction in HF was confirmed by echocardiography. IL-17A concentration in plasma and cerebrospinal fluid (CSF) was measured by ELISA and mRNA for IL-17A, IL-17F, tumor necrosis factor-α (TNF-α), IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and stromal cell-derived factor-1 (SDF-1) in PVN was measured by real-time qPCR. Compared with Sham rats, HF rats had significantly (*P<0.05) increased IL-17A level in plasma (3.57±0.19* vs 18.4 ± 3.57 pg/ml) and CSF (2.70± 0.34 * vs 6.96 ± 1.08 pg/ml). IL-17A level in CSF was correlated (R2=0.86, p<0.01) with IL-17A level in plasma. The mRNA levels of IL-17A (2.53 ± 0.28* vs 1.02± 0.11, fold change) and IL-17F (2.24 ± 0.22* vs 1.01 ± 0.09) were also higher in HF vs. Sham rats. Immunostaining revealed that IL-17RA was upregulated in the PVN in HF compared with Sham animals. In HF pretreated with bilateral PVN microinjections of an IL-17RA siRNA AAV virus and studied two week later, the mRNA level of TNF-α (1.44 ± 0.18* vs. 2.25 ± 0.21), IL-1β (1.72 ± 0.21* vs. 2.77 ± 0.25), IL-6 (1.60 ± 0.17 * vs 2.41 ± 0.21), MCP-1 (2.09 ± 0.18* vs 3.19 ± 0.27), MIP-α (1.62 ± 0.15* vs 2.39 ± 0.22) and SDF-1 (1.68 ± 0.24* vs 2.72 ± 0.23) were significantly reduced in the PVN compared with the HF rats pretreated with a scrambled siRNA virus. Sham rats without any treatments served as control. Knockdown efficiency of IL-17RA siRNA was confirmed by a reduction (-55%) of IL-17RA mRNA level in the PVN. These data indicated that IL-17A increases in HF and upregulates the expression of cytokines and chemokines in the brain. The increased IL-17A advances central inflammatory condition in HF probably by evoking the production of various inflammatory mediators. IL-17A is a potential target for therapeutic intervention in HF.

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

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

Long non‑coding RNA HOTAIR promotes the progression of synovial sarcoma through microRNA‑126/stromal cell‑derived factor‑1 regulation

The long non-coding RNA (lncRNA) HOTAIR is an oncogene, that has been reported to be aberrantly expressed in multiple types of malignant tumor tissues. However, its expression and association with synovial sarcoma (SS) remains unclear. The present study aimed to elucidate the expression level of HOTAIR in SS tissues and also identify its role. Reverse transcription-quantitative PCR was used to detect the expression level of HOTAIR and microRNA (miR)-126 in 54 tissue samples from patients with SS, in 10 tissue samples from synovium tissues of normal patients, and in SW982 cells. The protein expression level was measured using western blot analysis and cellular immunofluorescence. Cellular proliferation, invasion and migration were assessed using MTT, Transwell and wound healing assays, respectively. HOTAIR was expressed at high levels in SS tissues. In contrast, miR-126 was expressed at low levels in SS tissues, and was negatively correlated with HOTAIR expression. HOTAIR knockdown in SW982 cells inhibited cellular proliferation in vitro, but also significantly increased the ratio of cells in the G1/G0 phase of the cell cycle, and decreased the ratio of cells in the G2/S phase. In addition, HOTAIR knockdown inhibited the invasion and migration of the SW982 cells, as observed in the Transwell and wound healing assays. Furthermore, HOTAIR knockdown increased miR-126 expression level and decreased the expression level of stromal cell-derived factor-1 (SDF-1) at the protein level. On the other hand, while miR-126-mimic decreased the protein expression level of SDF-1, miR-126-inhibitor increased its expression level in SW982 cells. Notably, HOTAIR knockdown or SDF-1 knockout significantly decreased the protein expression levels of CDK1, CDK2, cyclin D1, MMP-9, vimentin and N-cadherin, and significantly increased the protein expression levels of p21, p53 and E-cadherin in SW982 cells. HOTAIR was highly expressed in SS tissues, wherein it could promote the proliferation, invasion and migration of SS cells by increasing the expression of SDF-1 via miR-126 inhibition.