Brain-Derived Exosomal CircRNAs in Plasma Serve as Diagnostic Biomarkers for Acute Ischemic Stroke.

Acute ischemic stroke (AIS), commonly known as stroke, is a debilitating condition characterized by the interruption of blood flow to the brain, resulting in tissue damage and neurological deficits. Early diagnosis is crucial for effective intervention and management, as timely treatment can significantly improve patient outcomes. Therefore, novel methods for the early diagnosis of AIS are urgently needed. Several studies have shown that bioactive molecules contained in extracellular vesicles, especially circRNAs, could be ideal markers for the diagnosis of many diseases. However, studies on the effects of exosomes and their circRNAs on the development and prognosis of AIS have not been reported extensively. Therefore, we explored the feasibility of using circRNAs in plasma brain-derived exosomes as biomarkers for AIS. By high-throughput sequencing, we first identified 358 dysregulated circRNAs (including 23 significantly upregulated circRNAs and 335 significantly downregulated circRNAs) in the plasma brain-derived exosomes of the brain infarct patient group compared to those of the noninfarct control group. Five upregulated circRNAs (hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808, and hsa_circ_0000097) were selected for further validation via Real-Time Quantitative Reverse Transcription PCR (qRT‒PCR) in a larger cohort based on the exclusion criteria of log2FC > 1, p < 0.05 and measurable expression. We found that the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were significantly upregulated in AIS patients and could serve as potential biomarkers for AIS with high specificity and sensitivity. Moreover, the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were also found to be positively correlated with National Institutes of Health Stroke Scale (NISS) and modified Rankin scale (mRS) scores, which indicated that the presence of these circRNAs in plasma brain-derived exosomes could also determine the progression of AIS.

Latent and incubation periods of Delta, BA.1, and BA.2 variant cases and associated factors: a cross-sectional study in China.

BACKGROUND: The latent and incubation periods characterize the transmission of infectious viruses and are the basis for the development of outbreak prevention and control strategies. However, systematic studies on the latent period and associated factors with the incubation period for SAS-CoV-2 variants are still lacking. We inferred the two durations of Delta, BA.1, and BA.2 cases and analyzed the associated factors. METHODS: The Delta, BA.1, and BA.2 (and its lineages BA.2.2 and BA.2.76) cases with clear transmission chains and infectors from 10 local SAS-CoV-2 epidemics in China were enrolled. The latent and incubation periods were fitted by the Gamma distribution, and associated factors were analyzed using the accelerated failure time model. RESULTS: The mean latent period for 672 Delta, 208 BA.1, and 677 BA.2 cases was 4.40 (95%CI: 4.24 ~ 4.63), 2.50 (95%CI: 2.27 ~ 2.76), and 2.58 (95%CI: 2.48 ~ 2.69) days, respectively, with 85.65% (95%CI: 83.40 ~ 87.77%), 97.80% (95%CI: 96.35 ~ 98.89%), and 98.87% (95%CI: 98.40 ~ 99.27%) of them starting to shed viruses within 7 days after exposure. In 405 Delta, 75 BA.1, and 345 BA.2 symptomatic cases, the mean latent period was 0.76, 1.07, and 0.79 days shorter than the mean incubation period [5.04 (95%CI: 4.83 ~ 5.33), 3.42 (95%CI: 3.00 ~ 3.89), and 3.39 (95%CI: 3.24 ~ 3.55) days], respectively. No significant difference was observed in the two durations between BA.1 and BA.2 cases. After controlling for the sex, clinical severity, vaccination history, number of infectors, the length of exposure window and shedding window, the latent period [Delta: exp(ß) = 0.81, 95%CI: 0.66 ~ 0.98, p = 0.034; Omicron: exp(ß) = 0.82, 95%CI: 0.71 ~ 0.94, p = 0.004] and incubation period [Delta: exp(ß) = 0.69, 95%CI: 0.55 ~ 0.86, p < 0.001; Omicron: exp(ß) = 0.83, 95%CI: 0.72 ~ 0.96, p = 0.013] were significantly shorter in 18 ~ 49 years but did not change significantly in ≥ 50 years compared with 0 ~ 17 years. CONCLUSION: Pre-symptomatic transmission can occur in Delta, BA.1, and BA.2 cases. The latent and incubation periods between BA.1 and BA.2 were similar but shorter compared with Delta. Age may be associated with the latent and incubation periods of SARS-CoV-2.

Ultra-Bend-Resistant 4-Core Simplex Cable Used for Short-Reach Dense Spatial Division Multiplexing Optical Transmission.

We optimized and fabricated an ultra-bend-resistant 4-core simplex cable (SXC) employing 4-core multicore fiber (MCF) suitable for short-reach dense spatial division multiplexing (DSDM) optical transmission in the O-band. The characteristics of transmission loss, macro-bending and cross-talk (XT) between adjacent cores after cabling were firstly clarified. By introducing the trapezoid index and optimizing the cabling process, the maximum values of added XT of 1.17 dB/km due to 10 loops with a bending radius of 6 mm imposed over the 4-core SXC and a macro-bending loss of 0.37 dB/10 turns were, respectively, achieved.P Then, the optical transmission with low bit error rate (BER) was presented using a 100GBASE-LR4 transceiver over the 1.2 km long 4-core SXC. The excellent bending resistance of the 4-core SXC may pave the way for a reduction in space pressure and increase in access density on short-reach optical interconnect (OI) based on DSDM.

Association of plasma galectin-3 and fetuin-A levels with diabetic retinopathy in type 2 diabetes mellitus patients.

INTRODUCTION: Galectin-3 (Gal-3) and fetuin-A (Fet-A) are cytokines that participate in inflammation and insulin resistance. Previous studies have found that altered Gal-3 and Fet-A levels in circulation correlate with diabetic complications. However, whether they are all associated with diabetic retinopathy (DR) has been little investigated. The aim of this study was to assess plasma Gal-3 and Fet-A concentrations, and to investigate their associations with the presence of DR in type 2 diabetes mellitus (T2DM) patients. MATERIAL AND METHODS: A total of 100 T2DM patients were enrolled, among which there were 50 patients without DR (non diabetic retinopathy, NDR group) and 50 patients with DR (DR group). Clinical parameters were collected, and plasma Gal-3 and Fet-A levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Both Gal-3 and Fet-A were found to be increased in DR patients with respect to NDR controls, and Gal-3 correlated positively with Fet-A. Bivariate correlation analysis revealed that Gal-3 levels were positively correlated with haemoglobin A1c (HbA1c), while Fet-A correlated negatively with fasting C peptide (FC-P) and positively with homocysteine (Hcy). Binary logistic regression suggested that elevated Gal-3 and Fet-A levels were related to increased risk of DR. ROC curve displayed that the combination of Fet-A and Gal-3 exhibited better diagnostic value for DR. CONCLUSIONS: Both Gal-3 and Fet-A were elevated in the circulation of DR patients, and they were positively associated with the occurrence of DR. The combination of 2 indicators showed better diagnostic value for DR.

Updates on RPE cell damage in diabetic retinopathy (Review).

Diabetic retinopathy (DR) is a microvascular complication of diabetes. The retinal pigment epithelium (RPE) forms the outer layer of the blood­retinal barrier and serves a role in maintaining retinal function. RPE cell injury has been revealed in diabetic animal models, and high glucose (HG) levels may cause damage to RPE cells by increasing the levels of oxidative stress, promoting pro­inflammatory gene expression, disrupting cell proliferation, inducing the endothelial­mesenchymal transition, weakening tight conjunctions and elevating cell death mechanisms, such as apoptosis, ferroptosis and pyroptosis. Non­coding RNAs including microRNAs, long non­coding RNAs and circular RNAs participate in RPE cell damage caused by HG levels, which may provide targeted therapeutic strategies for the treatment of DR. Plant extracts such as citrusin and hesperidin, and a number of hypoglycemic drugs, such as sodium­glucose co­transporter 2 inhibitors, metformin and glucagon­like peptide­1 receptor agonists, exhibit potential RPE protective effects; however, the detailed mechanisms behind these effects remain to be fully elucidated. An in­depth understanding of the contribution of the RPE to DR may provide novel perspectives and therapeutic targets for DR.

Omentin-1 and diabetes: more evidence but far from enough.

AIMS AND BACKGROUND: Omentin-1 (oment-1) is a type of adipokines that is mainly expressed in visceral fat tissue. Based on accumulating evidence, oment-1 is closely related to diabetes and its complications. However, so far data about oment-1 and diabetes is fragmented. In this review, we focus on the role of oment-1 on diabetes, including its possible signalling pathways, the correlation of circulating omens-1 levels with diabetes and its complications. METHODS: The web of PubMed was searched for articles of relevant studies published until February, 2023. RESULTS AND CONCLUSIONS: Oment-1 might exert its effects by inhibiting the NF-κB pathway and activating the Akt and AMPK-dependent pathways. The level of circulating oment-1 is negatively correlated with the occurrence of type 2 diabetes and some complications, including diabetic vascular disease, cardiomyopathy, and retinopathy, which can be affected by anti-diabetic therapies. Oment-1 could be a promising marker for screening and targeted therapy for diabetes and its complications; however, more studies are still needed.

A Novel Pathway of Functional microRNA Uptake and Mitochondria Delivery.

Extracellular microRNAs (miRNAs) play a critical role in horizontal gene regulation. Uptake of extracellular miRNAs by recipient cells and their intracellular transport, however, remains elusive. Here RNA phase separation is shown as a novel pathway of miRNA uptake. In the presence of serum, synthetic miRNAs rapidly self-assembly into ≈110 nm discrete nanoparticles, which enable miRNAs' entry into different cells. Depleting serum cationic proteins prevents the formation of such nanoparticles and thus blocks miRNA uptake. Different from lipofectamine-mediated miRNA transfection in which majority of miRNAs are accumulated in lysosomes of transfected cells, nanoparticles-mediated miRNA uptake predominantly delivers miRNAs into mitochondria in a polyribonucleotide nucleotidyltransferase 1(PNPT1)-dependent manner. Functional assays further show that the internalized miR-21 via miRNA phase separation enhances mitochondrial translation of cytochrome b (CYB), leading to increase in adenosine triphosphate (ATP) and reactive oxygen species (ROS) reduction in HEK293T cells. The findings thus reveal a previously unrecognized mechanism for uptake and delivery functional extracellular miRNAs into mitochondria.

Effects of Multi-Pass Turning on Stress Corrosion Cracking of AISI 304 Austenitic Stainless Steel.

Austenitic stainless steels are extensively used in mechanical engineering. The machined surface integrity has an essential influence on the stress corrosion cracking (SCC) performance of stainless steels. In this paper, the effects of multi-pass turning on the SCC susceptibility of AISI 304 austenitic stainless steel were investigated by correlating the SCC crack density to the machining-induced surface characteristics in terms of roughness, micro-hardness, and residual stress. In the multi-pass turning, the surface roughness and residual stress were the least after the double pass turning, and the surface micro-hardness was the maximum after the triple-pass turning. The SCC susceptibility was evaluated after SCC tests in boiling MgCl2 solution. The results showed that the weakest SCC sensitivity was observed in double-pass turning 304 stainless steel, while the most susceptible SCC was found in triple-pass turning. Compared with the double-pass turning, the increase in SCC sensitivity of triple-pass turning was attributed to the larger roughness, higher micro-hardness and greater residual tensile stresses.

Fabrication and Characterization of an Optimized Low-Loss Two-Mode Fiber for Optoacoustic Sensing.

An optimized multi-step index (MSI) 2-LP-mode fiber is proposed and fabricated with low propagation loss of 0.179 dB/km, low intermodal crosstalk and excellent bend resistance. We experimentally clarified the characteristics of backward Brillouin scattering (BBS) and forward Brillouin scattering (FBS) induced by radial acoustic modes (R0,m) in the fabricated MSI 2-LP-mode fiber, respectively. Via the use of this two-mode fiber, we demonstrated a novel discriminative measurement method of temperature and acoustic impedance based on BBS and FBS, achieving improved experimental measurement uncertainties of 0.2 °C and 0.019 kg/(s·mm2) for optoacoustic chemical sensing. The low propagation loss of the sensing fiber and the new measurement method based on both BBS and FBS may pave the way for long-distance and high spatial resolution distributed fiber sensors.

A novel method to purify small RNAs from human tissues for methylation analysis by LC-MS/MS.

Methylation modification of small RNAs, including miRNA, piRNA, and tsRNA, is critical for small RNA biogenesis and biological function. Methylation of individual small RNA can be defined by liquid chromatography-coupled with mass spectrometry (LC-MS/MS). However, LC-MS/MS analysis requires a high purity of individual small RNA. Due to the difficulty of purifying specific small RNA from tissues or cells, the progress in characterizing small RNA methylation by LC-MS/MS is limited. Here, we report a novel method that can efficiently purify small RNA from human tissues for LC-MS/MS analysis. This method includes two steps: 1) pull down the target small RNA by incubating total small RNAs (18-24 nt) extracted from human tissues with a biotinylated antisense oligonucleotide of the target small RNA, followed by capturing the binding duplex of biotinylated antisense and small RNA via streptavidin magnetic beads, and 2) protect the target small RNA by pairing it with a single-strand DNA, which sequence is complementary to the target small RNA, to form a DNA/RNA hybrid double-strand, followed by sequential digestion with exonuclease I, nuclease S1, and DNase I, respectively. Furthermore, employing a mixture of four pairs of synthetic methylated and non-methylated small RNAs, we further refined this two-step method by optimizing the nuclease S1 treatment condition. With this method, we successfully purified miR-21-5p, miR-26-5p, piR-020485, and tsRNA from human lung and sperm tissue samples and analyzed their 2'-O-methylation modification at the 3'-end by LC-MS/MS.

Inhibition of galectin-3 ameliorates high-glucose-induced oxidative stress and inflammation in ARPE-19 cells.

PURPOSE: Retinal pigment epithelium (RPE) has been found to be participated in the pathogenesis of DR in recent years. Galectin-3 (Gal-3) is involved in many diabetic complications and ophthalmological diseases. However, the role of Gal-3 in RPE cells in DR remains unknown. This study aims to investigate the role of Gal-3 in ARPE-19 cells under high glucose treatment. MATERIALS AND METHODS: ARPE-19 cells were cultured under normal or high glucose (HG) for 48 h. Expression of Gal-3 was inhibited by Si-Gal-3 transfection. Apoptosis was checked by flow cytometry. Oxidative stress was checked by measuring ROS, MDA levels, and SOD activities. Occludin and ZO-1 expression were checked by immunofluorescence staining. Genes involved in inflammatory response were measured by real-time PCR and Western blot. RESULTS: Gal-3 expression could be increased by HG treatment in ARPE-19 cells. Gal-3 knockdown might reduce oxidative stress, apoptosis, and gene expression of VCAM-1, ICAM-1, and integrin-ß1 induced by HG treatment. The gene expression of IL-1ß could be markedly promoted by HG treatment and this increasement was partly alleviated by Gal-3 knockdown only at the mRNA level. The reduced expression of ZO-1 and occludin caused by HG could also be improved by Gal-3 knockdown. CONCLUSION: Gal-3 participated in increased oxidative stress and inflammatory response caused by HG in ARPE-19 cells.

Long non­coding RNA MALAT1 is involved in retinal pigment epithelial cell damage caused by high glucose treatment.

The present study aimed to explore the role of long non­coding RNA metastasis associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) in high glucose (HG)­induced ARPE­19 cell damage. ARPE­19 cells were cultured and treated with HG (25 mmol/l glucose). MALAT1 expression was silenced following transfection of small interfering RNA. Cell apoptosis was measured using flow cytometry. The cellular levels of reactive oxygen species (ROS), malondialdehyde and superoxide dismutase activity were all measured to examine oxidative stress. Gene expression levels of MALAT1 were determined by reverse transcription­quantitative (RT­q)PCR, while expression of tumor necrosis factor (TNF)­α, monocyte chemotactic protein 1 (MCP­1), intercellular cell adhesion molecule 1 (ICAM­1) and vascular endothelial growth factor (VEGF) was detected using RT­qPCR and western blotting. MALAT1 expression was markedly increased in ARPE­19 cells treated with HG. HG treatment caused increased apoptosis and elevated ROS­induced stress in ARPE­19 cells and these effects could be partly attenuated by MALAT1 knockdown. Increased gene expression levels of TNF­α, MCP­1, ICAM­1 and VEGF induced by HG were also alleviated by MALAT1 inhibition. Therefore, lncRNA MALAT1 is the key factor in ARPE­19 cell damage caused by HG and may be a promising therapeutic target for clinical DR therapy. However, further studies are still required to reveal the detailed mechanisms underlying lncRNA MALAT1 function.

Cladding softened fiber for sensitivity enhancement of distributed acoustic sensing.

Fiber-optic distributed acoustic sensing (DAS) technology with high spatial and strain resolutions has been widely used in many practical applications. New methods to enhance the phase sensitivity of sensing fiber are worth exploring to further improve DAS performances, although the standard single-mode fiber (SSMF) has been widely used for DAS technology. In this work, we propose and demonstrate the concept of enhancing the phase sensitivity of DAS by softening the cladding of the sensing fiber, for the first time. The theoretical analysis indicates that softening sensing fiber cladding is an effective way to improve phase sensitivity. Thus, we fabricated cladding softened fibers (CSFs) and tested their phase sensitivities experimentally. According to the results, it is found that the phase sensitivity of the CSF with 0.48 WT% phosphorus-doping concentration and 80 µm cladding diameter is 22% and 54% higher than that of the non-phosphorus-doping fiber with 80 µm cladding diameter and SSMF, respectively. The results show that by reducing fiber cladding Young's modulus with higher phosphorus-doping concentration, the DAS phase sensitivity can be enhanced effectively, verifying the theoretical analysis. Also, we found that the phase sensitivity enhancement of the sensing fiber has a linear relationship with the cladding phosphorus-doping concentration, i.e. Young's modulus. In conclusion, the reported CSF paves a way for improving the DAS phase sensitivity and would be applied to other major optical fiber sensing systems as a better sensing element over SSMF due to the enhancement in the elasto-optical effect of the sensing fiber.

Effects of neonatal dexamethasone administration on cardiac recovery ability under ischemia-reperfusion in 24-wk-old rats.

BACKGROUND: Evaluations of stress-induced cardiac functional alterations in adults after neonatal glucocorticoid (GC) treatment have been limited. In the present study, we evaluated adult cardiac functional recovery during postischemic reperfusion and measured cardiac gene expression involved energy metabolism in rats neonatally treated with dexamethasone (DEX). METHOD: Male Wistar rats were injected DEX in first 3 d after birth and controls were received saline (SAL). At 24 wk of age, insulin tolerance tests were performed, plasma lipid levels were measured, and left ventricular function and myocardial infarct size were evaluated. Expressions of genes involved in cardiac energy metabolism were measured by quantitative real-time polymerase chain reaction (PCR) and western blot. RESULTS: In 24-wk-old rats, neonatal DEX administration caused dyslipidemia, impaired cardiac recovery function and increased size of infarction, decreased cardiac expression of glucose transporter 4(GLUT4), peroxisome proliferative-activated receptor gamma coactivator 1α (PGC-1α) and ratios of phospho-forkhead box O1/forkhead box O1 (p-FoxO1/FoxO1) and phospho AMP-activated protein kinase/AMP-activated protein kinase (p-AMPK/AMPK) but increased pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) expression compared with controls. CONCLUSION: Neonatal DEX administration impairs cardiac functional recovery during reperfusion following ischemia in 24-wk-old rats. Reduced cardiac glucose utilization may contribute to the long-term detrimental effects caused by neonatal DEX treatment.

SIRT1 and insulin resistance.

Sirtuin 1 (SIRT1) is a prototype mammalian NAD(+)-dependent protein deacetylase that has emerged as a key metabolic sensor in various metabolic tissues. Growing evidence suggests that SIRT1 regulates glucose and lipid metabolism through its deacetylase activity. In this review, we have summarized the recent progress in SIRT1 research with a particular focus on the role of SIRT1 in insulin resistance at different metabolic tissues. Recent data indicate that activated SIRT1 improves the insulin sensitivity of liver, skeletal muscle and adipose tissues and protects the function and cell mass of pancreatic ß-cells. These findings suggest that SIRT1 might be a new therapeutic target for the prevention of disease related to insulin resistance, such as metabolic syndrome and type 2 diabetes mellitus.

Robust Indoor Human Activity Recognition Using Wireless Signals.

Wireless signals-based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI) of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP) and access points (AP). First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions' CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO) signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM) based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

[Endoscope-assisted repair of pediatric blowout fractures of orbital floor with autologous bone fragment].

OBJECTIVE: To explore the clinical efficacy of endoscopic repairing pediatric blowout fracture of orbital floor with autologous bone fragment. METHODS: A total of 12 cases with blowout fractures of orbital floor between March 2010 and June 2012 at Third Hospital of HeBei Medical University were reviewed. They underwent nasal endoscopic reconstruction of autologous bone fragment in situ. Medicinal biomaterial glue was used for fixation. A 6-month follow-up was performed and the therapeutic efficacies of anatomic and functional recovery were evaluated. RESULTS: No further vision loss or infection occurred postoperatively. Diplopia disappeared over a period of 3 days to 6 months. At 3 months post-operation, diplopia vanished completely (n = 9), and peripheral vision diplopia persisted (n = 3). Only 1 case had still peripheral vision diplopia at 6 months. Enophthalmos: ≥ 2 mm (n = 1), 1 mm (n = 3) for one week after surgery and only 1 mm (n = 1) at one month follow-up. Passive traction test was negative in all cases and computed tomograph (CT) revealed no bone redislocation postoperatively. CONCLUSION: Endoscopic repair of pediatric blowout fracture of orbital floor with autologous bone fragment in situ is both effective and safe.

Early life factors and type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and its aetiology involves a complex interplay between genetic, epigenetic, and environmental factors. In recent years, evidences from both human and animal experiments have correlated early life factors with programming diabetes risk in adult life. Fetal and neonatal period is crucial for organ development. Many maternal factors during pregnancy may increase the risk of diabetes of offsprings in later life, which include malnutrition, healthy (hyperglycemia and obesity), behavior (smoking, drinking, and junk food diet), hormone administration, and even stress. In neonates, catch-up growth, lactation, glucocorticoids administration, and stress have all been found to increase the risk of insulin resistance or T2DM. Unfavorable environments (socioeconomic situation and famine) or obesity also has long-term negative effects on children by causing increased susceptibility to T2DM in adults. We also address the potential mechanisms that may underlie the developmental programming of T2DM. Therefore, it might be possible to prevent or delay the risk for T2DM by improving pre- and/or postnatal factors.

Murine corneal stroma cells suppress bone marrow-derived dendritic cells maturation in vitro.

BACKGROUND: Prostaglandin E2 (PGE(2)) is a key modulator of dendritic cells (DCs) function, and cornea-derived transforming growth factor beta 2 (TGF-ß(2)) promotes the generation of phenotypically and functionally immature DCs. Therefore, this study was carried out to investigate whether PGE(2) is involved in the suppressive effect on DCs maturation mediated by corneal stroma cells (CSCs) and whether PGE(2) and TGF-ß(2) have additive effects in this immunosuppressive mechanism. METHODS: Bone marrow-derived DCs (BM-DCs), splenic T cells and CSCs culture supernatant were obtained from mice via various protocols. After that, the level of PGE(2) in CSCs culture supernatant was analyzed by enzyme-linked immunosorbent assay. Then, immature BM-DCs pretreated by E-prostanoid 2 receptor antagonist AH6809 or dimethyl sulfoxide were induced to mature in the presence of lipopolysaccharide, with or without CSCs culture supernatant. In parallel experiments, neutralizing TGF-ß(2) antibody or normal goat IgG was added into the supernatant. Next, the cellular surface markers for DCs maturation, including CD80, CD86, and major histocompatibility complex class II (MHCII), were analyzed by flow cytometry; the capability of stimulating the proliferation of T lymphocytes was evaluated by allogeneic mixed lymphocyte reactions and the function of endocytosis was assessed by fluorescein isothiocyanate-dextran uptake. RESULTS: Higher concentration of PGE(2) was detected in CSCs culture supernatant than in the fresh medium. In addition, compared with control group, after treated with the supernatant in the mature stage, BM-DCs displayed lower expression of CD80, CD86 and MHC II, lower T cell stimulatory capacity and higher endocytosis function. However, after the application of AH6809, BM-DCs partially regained T cell stimulatory capacity and expression of CD86 and MHC II, but partially lost endocytic activity. Moreover, after the application of AH6809 and neutralizing TGF-ß(2) antibody, the result of statistical analysis indicated that there was a statistical difference of interaction in the expression of MHC II and T cell stimulatory capacity. CONCLUSIONS: PGE(2) contributes to the suppressive effect on BM-DCs maturation mediated by CSCs in vitro, and PGE(2) and TGF-ß(2) have additive effects on the immunosuppression of BM-DCs.