[Research advances on the mechanism of oral mucosal stem cells in promoting wound healing].

Wound healing is a complex process that requires the participation of multiple cells and cytokines. During the process of wound healing, abnormality in any stage of the process may lead to the development of a chronic refractory wound. Research has confirmed that various stem cells can promote wound healing, but some stem cells are limited in clinical application due to difficulties in isolation, susceptibility to apoptosis, ethical and legal issues. Oral mucosal stem cells (OMSCs) can avoid the above problems. This type of stem cells has the characteristics of embryonic stem cells, immune regulatory ability, and strong homogeneity. It plays an important role in the process of scarless oral wound healing, and has become a research hotspot in promoting wound healing and reducing scar formation. This article reviews the research on the mechanism, clinical application prospects, and current problems of OMSCs in promoting wound healing.

[Research advances on platelet-rich blood products combined with biological materials in wound repair].

The efficient management of wounds is the focus of current research. In addition to conventional wound management and necessary surgery, the role of pro-healing drugs in wound treatment has gradually been emphasized. Platelet-rich blood products that is rich in a variety of biologically active molecules are considered as a low-cost and safe therapy in promoting tissue healing, and have great development prospects in the field of regenerative medicine. However, due to the lack of standard preparation and management and the unstable activities of the biomolecules in them, the therapeutic effects of platelet-rich blood products are uneven. In order to solve these problems, researches related to the protection and delivery of biologically active molecules in platelet-rich blood products by biomaterials have gradually increased in recent years, which is also one of the latest trends in wound treatment research. This article first briefly introduces the types of platelet-rich blood products, then outlines the latest research progress achieved by their combination with biomaterials, and finally summarizes the research progress and future research directions of the combination approach in wound treatment.

Up-regulation of SNHG15 facilitates cell proliferation, migration, invasion and suppresses cell apoptosis in breast cancer by regulating miR-411-5p/VASP axis.

OBJECTIVE: Breast cancer (BC) is an intractable cancer with a rising incidence. Small nucleolar RNA host gene 15 (SNHG15) is a novel biomarker of multiple cancers. However, the molecular mechanism of SNHG15 during oncogenesis of BC is still poorly understood. MATERIALS AND METHODS: Expression of SNHG15, microRNA (miR)-411-5p and vasodilator stimulated phosphoprotein (VASP) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by colony formation and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was determined by flow cytometry and caspase-3 activity assay. Cell migration and invasion were examined by transwell assay. The interaction between miR-411-5p and SNHG15 or VASP was validated by dual-luciferase reporter assay. Protein expression of VASP, B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP-9, MMP-14) was measured by Western blot. Xenograft mice were established by subcutaneously injecting SKBR-3 cells transfected with sh-SNHG15 and sh-NC. RESULTS: SNHG15 and VASP were over-expressed whereas miR-411-5p was low-expressed in BC tumors and cells compared with the normal counterparts. Next, SNHG15 knockdown attenuated cell proliferation, migration, invasion and stimulated cell apoptosis in BC. In addition, SNHG15 acted as a sponge while VASP acted as a target of miR-411-5p. Rescue experiment revealed that miR-411-5p inhibitor could alleviate SNHG15 silencing-induced inhibitive effects on cell proliferation, migration, invasion and promotive effects on cell apoptosis. Similarly, VASP attenuated the regulatory effects of SNHG15 silencing on BC cell progression. Furthermore, SNHG15 elimination hindered tumor growth in vivo. CONCLUSIONS: SNHG15 contributes to BC cell progression by sponging miR-411-5p and enhancing VASP expression, providing essential biomarkers for BC therapy.

A comprehensive understanding of ovarian carcinoma survival prognosis by novel biomarkers.

OBJECTIVE: Ovarian cancer is one of the most common causes of cancer-related deaths in women. Many studies show that dysregulated gene expression plays a key role in tumorigenesis and development. Therefore, a comprehensive understanding of ovarian serous cystadenocarcinoma survival prognosis is needed. PATIENTS AND METHODS: A large number of high-dimensional RNA-sequencing files and clinical datasets collected from the Genomic Data Commons Data Portal were utilized to identify novel potential biomarkers for determining the prognosis of patients with ovarian serous cystadenocarcinoma (OVSC). We adopted a new strategy to identify these biomarkers by integrating co-expression network analysis and the Kaplan-Meier estimation with a non-parametric bootstrapping procedure. RESULTS: Functional enrichment analysis of gene modules of interest revealed several dysregulated genes in OVSC, suggesting a close relationship between hormones and angiogenesis. In combination with this comprehensive approach, 14 genes, including ABCA10, DCX, LRRC30, ALX4, DKK4, SGCZ, ANKS4B, FHL5, SPRR2F, CHRNG, GABRR1, STMN2, CRHBP, and GSTM5, were shown to serve as candidate biomarkers for predicting the prognosis of patients with OVSC. CONCLUSIONS: The current study identified several valuable prognostic biomarkers and several potential therapeutic targets for treating OVSC.

[Propensity-matched comparison of laparoscopic and open radical cystectomy for female patients with bladder cancer].

OBJECTIVE: To compare the perioperative and oncologic outcomes of female patients receiving laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC). METHODS: Retrospective review of 91 consecutive female patients with urothelial carcinoma of bladder undergoing radical cystectomy at a single academic institution from 2006 to 2017. Those female patients received open radical cystectomy were matched to the patients who underwent laparoscopic radical cystectomy by using propensity score matching in 1 ∶1 ratio. The matching factors included age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, pathologic stage and pathologic nodal stage. The perioperation and oncology characteristics were compared, and Kaplan-Meier method was used to analyze the overall survival (OS), cancer specific survival (CSS) and progression-free survival (PFS) estimates. Finally, we did a sensitive analysis by using multivariable COX regression of all the patients, adjusting for the matching factors. RESULTS: There were 65 ORC and 26 LRC patients identified in this cohort with urothelial carcinoma of bladder, the median follow-up time was 38 months (interquartile range 18-69). The age (P<0.001) and ASA scores (P=0.018) were less for LRC before being matched. There were 22 LRC and 22 ORC patients matching successfully. Before being matched, the estimate blood loss (P=0.005), transfusion rate (P<0.001) and total complications rate (P=0.015) were less for LRC, and the lymph nodes yield was greater for LRC, but there were no differences in OS (P=0.698), CSS (P=0.942) and PFS (P=0.837) between the two groups. After being matched, the estimate blood loss (P=0.009), transfusion rate (P=0.001) and total complications rate (P=0.040) were less for LRC, but there was no difference in the lymph nodes yield. Besides, there were no statistic differences in OS (P=0.432), CSS (P=0.429) and PFS (P=0.284) between the two groups. In addition, in multivariable COX regression analysis, surgical approaches (LRC/ORC) were not found to be a predictor of OS (HR 1.134, 95%CI 0.335-3.835, P=0.839), CSS (HR 1.051, 95%CI 0.234-4.719, P=0.949) and PFS (HR 0.538, 95%CI 0.138-2.095, P=0.371) of the female patients with urothelial carcinoma of bladder. CONCLUSION: It is advantageous for laparoscopic radical cystectomy in terms of estimating blood loss, transfusion rate and complication rate. But there was no evidence that laparoscopic radical cystectomy for female patients with bladder cancer had a better oncologic prognosis than open radical cystectomy from this study.

Circ-ITCH regulates triple-negative breast cancer progression through the Wnt/ß-catenin pathway.

Recent studies indicate that circular RNA (circRNA) is involved in tumorigenesis, but its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, we characterized the role of circ-ITCH in TNBC and found that circ-ITCH was significantly down-regulated in TNBC tissues and cell lines and closely associated with poor prognosis. We therefore constructed the MDA-MB-231 and BT-549 TNBC cell lines stably expressing circ-ITCH by lentiviral vectors to determine its underlying mechanisms in TNBC progression. Most importantly, over-expression of circ-ITCH remarkably inhibited TNBC proliferation, invasion and metastasis both in vitro and in vivo. Mechanistically, we found that circ-ITCH acts as a sponge for miR-214 and miR-17 to increase expression of its ITCH linear isoform, thereby inactivating Wnt/ß-catenin signaling. Our combined results show for the first time that circ-ITCH is a tumor suppressor, a promising prognostic biomarker in TNBC and that its restoration could well be a successful strategy in TNBC.

Effect of Deltex-1 on proliferation and differentiation of bone marrow mesenchymal stem cells into smooth muscle cells.

OBJECTIVE: To investigate the effect of Deltex-1 on proliferation and differentiation of bone marrow mesenchymal stem cells (bMSCs) into smooth muscle cells (SMCs). MATERIALS AND METHODS: bMSCs of rat were isolated from bone marrow, cultured and identified. The effect of Deltex-1 on the proliferation of bMSCs infected with adenovirus vector pAd/Deltex-1 was detected by cell count kit-8 (CCK-8). The expression of smooth muscle myosin heavy chain (SM-MHC), that is one of the markers of SMCs in bMSCs without treatment, with Deltex-1 virus infection or empty virus infection and co-cultured with SMCs, were detected by immunofluorescence cytochemistry staining, RT-PCR and Western blotting. The same detection of bMSCs and SMCs without treatment was used as normal control, respectively. RESULTS: bMSCs of rat were isolated from bone marrow, cultured and identified. Compared with the control, the results of CCK-8 showed that the growth of bMSCs infected by Deltex-1 virus was slower, and began to appear more significant especially at 48 (p<0.05, p<0.01). The results of immunofluorescence cytochemistry, Real-time PCR and Western blot showed that bMSCs with Deltex-1 virus infection and co-cultured with SMCs significantly expressed SM-MHC, and weakly expressed Notch-1. CONCLUSIONS: The proliferation of bMSCs with Deltex-1 over-expression could be inhibited and its differentiation into smooth muscle cells could be promoted.

[Clinical features analysis of metanephric adenoma: a series of 16 cases].

Objective: To study the clinical characteristics, image findings, therapeutic method and prognosis of metanephric adenoma. Method: The clinical characteristic, image findings, operation methods and prognosis of 16 metanephric adenoma patients treated at Department of Urology, Peking University First Hospital from January 2004 to March 2016 were analyzed retrospectively. Results: There were 6 male and 10 female patients in the study. The mean age of patients was 33.7 years (ranging from 14 to 83 years). Two patients came to the hospital because of fever, while other 14 patients had no symptoms and found renal tumor by medical examination. One case was found polythemia vera and another 1 case showed mild anemia. Serum creatine of all the cases were in normal range. The tumor of 11 cases were at left side and 5 cases were at right. All patients took urinary tract ultrasound. Fifteen patients took CT examination. Among them, 14 cases were solid mass and 1 case was cystosolid.CT value was (41±4) HU. CT scan showed that the tumor was slight enhanced and CT value increased to (77±9) HU. Six patients took MRI examination. The MRI showed high or low signal of T1WI or T2WI scans.Tumor size was (4.7±3.9)cm (ranging from 1.7 to 17.5 cm). All 16 patients took operation and 11 of them took laparoscopic surgery while the other 5 cases took open surgery. Eleven cases took partial nephrectomy, 4 cases took nephrectomy and 1 case took nephroureterectomy. The surgical procedures were all successful and no complications occured during perioperative period. All cases were all confirmed metanephric adenoma by postoperative pathology and surgery cut edge were all negative. Immunohistochemical study showed that the positive rate of Vimentin, CD57, AE1/AE3, WT1, CK7 and AMACR respectively were 16/16, 15/16, 12/16, 10/16, 3/16 and 2/16. The median follow-up time of 16 cases was 44 months (ranging from 8 to 125 months) and none had recurrence or metastasis.One case died 125 months after surgery because of advanced age(83 years old). Conclusions: Metanephric adenoma is difficult to be diagnosed relying on clinical characteristics and image features. Pathology can help confirm the diagnosis. Partial nephrectomy is the first choice for operation and can achieve good prognosis. But it still needs a regular follow-up.

[Prognostic factors of patients with T2N0M0 upper tract urothelial carcinoma: a single-center retrospective study of 235 patients].

OBJECTIVE: To evaluate the impacts of the prognostic factors of T2N0M0 upper tract urothelial carcinoma (UTUC) for Chinese patients. METHODS: A retrospective study was conducted including 235 patients who were diagnosed with T2N0M0 UTUC in our hospital and received radical nephroureterectomy (RNU) or partial ureterectomy during January 2000 and December 2013. The 3 and 5-year cancer-specific survival rates and bladder recurrence-free survival rates of all the patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between the two were compared using the Log-rank test. Variables with significant differences in the univariate analysis were subjected to the multivariate analysis by Cox regression model. RESULTS: A total of 235 patients were included in this study, including 95 (40.4%) male patients and 140 (59.6%) female patients. The mean age was 66.73±10.49 years.The median follow-up time was 53 (rang: 3-142) months, and during the follow-up, 74 (31.5%) patients died of UTUC after a median of 35 months,and 96 (40.9%) patients developed intravesical recurrence after a median of 19.5 months. The 3 and 5-year cancer-specific survival rates of all the patients were 89.1% and 85.9%, respectively; the bladder recurrence-free survival rates were 85.5% and 80.2%, respectively. The independent prognostic factors of cancer-specific mortality were tumor age elder than 55 years (HR=3.138, 95%CI: 1.348-7.306, P=0.008) and diameter larger than 5 cm (HR=3.320, 95%CI: 1.882-5.857, P<0.001). The independent prognostic factors of bladder recurrence-free survival were ureter tumor (HR=1.757, 95%CI: 1.159-2.664, P=0.008) and lower tumor grade (HR=1.760, 95% CI: 1.151-2.692, P=0.009). CONCLUSION: T2N0M0 UTUC has a better cancer-specific survival. The intravesical recurrence was equivalent to non-muscle invasive UTUC but earlier. The tumor diameter larger than 5 cm and the patient age elder than 55 years were independently associated with cancer-specific mortality; the primary tumor located in ureter and lower tumor grade were more likely to develop intravesical recurrence.

[Diagnosis and treatment of T1a-T1b prostate cancer].

OBJECTIVE: To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of incidental (stage T1a-T1b) prostate cancer. METHODS: Seven hundred and seventy-one patients who underwent TURP from May 2004 to September 2013 were analyzed retrospectively. In our institution, TURP specimens should be totally submitted in an extensive sampling method. The tumor area was outlined by estimation of an experienced genitourinary pathologist and calculated by the image analysis system software (Image J 1.47 h). The tumor area was then multiplied by the thickness of tissue. The total sum of all tumor volume was the estimated tumor volume. The clinical and pathological factors, follow-up results were obtained and we aimed to collect information about the period of watchful waiting (WW), PSA progression status, intervention status during the follow-up, the reason for intervention on WW and the type of intervention. RESULTS: The average age of 771 patients was (71.3±5.9) years old, and the average BMI was (23.9±3.1) kg/m2, preoperative average tPSA was (4.4±2.8) µg/L. Eighty-six (11.2%) cases of incidental prostate cancer were detected. The patients in T1a group (77 cases, 89.5%) had tumor volumes of (12.3±12.6) mm3, and the patients in T1b group had tumor volumes of (105.1±41.8) mm3.The range of tumor volume was 0.4-180.2 mm3. The volume of all the 86 cases was less than 500 mm3 as the threshold of insignificant cancer. All the patients were managed by WW. The mean follow-up time was 88.9 (27.9-150.1) months.The Gleason score was <7 in 79 patients, and ≥7 in 7 patients. There was no significant difference in age, preoperative tPSA, preoperative PSAD, postoperative tPSA, prostate volume and TURP resection between T1a group and T1b group (P>0.05). Among 84 patients without follow-up losts, PSA progression occurred in 5 patients. One T1a patient underwent radical prostatectomy (RP) as an intervention, and 3 patients underwent hormone therapy. One patient in T1b group underwent radiotherapy for PSA progression and one was treated because of patient preference without evidence of disease progression. There were no patients who died due to prostate cancer. CONCLUSION: Eighty-six (11.2%) cases of incidental prostate cancer were detected. The tumor volume of all the cases was insignificant cancer.The clinical outcomes of IPCa were satisfactory with the initial treatment of WW in the Chinese population.

USF1 prompt melanoma through upregulating TGF-ß signaling pathway.

OBJECTIVE: The activation of TGF-ß signaling contributes to abnormal EMT process and upstream stimulatory family1 (USF1) was recently found to activate the expression of TGF-ß. However, the specific role of USF1 in melanoma has never been explored. MATERIALS AND METHODS: The expression of USF1 was analyzed using real-time PCR and Western blot. The changes of cell morphology were observed under a microscope. Cell migration was determined using in vitro scratch test. A specific siRNA was applied to knockdown of USF1. RESULTS: The mRNA and protein levels of USF1 were significantly enhanced in melanoma cell lines, 1205-Lu, DO4, WM3211, and WM278, compared with normal human melanocytes PIG1. Overexpression of USF1 induced demonstrated an elongated and spindle-shaped morphology in the 1205-Lu cells. Meanwhile, USF1 induced the expression of α-SMA, Vimentin and Fibronectin, while the epithelial marker, E-cadherin (E-cad), was significantly decreased. Furthermore, in vitro scratch test demonstrated that overexpression of USF1 markedly enhanced 1205-Lu cell migration capacity at 24 h and 48 h. More importantly, knockdown of USF1 could partially reverse TGF-ß1-treatment-induced changes of EMT markers as well as cell morphological changes. CONCLUSIONS: We first demonstrate that overexpression of USF1 prompts the EMT process through the accumulation of TGF-ß1 production in melanoma cells.

[Clinicopathological features and differential diagnosis of metanephric adenoma: a report of sixteen cases].

OBJECTIVE: To study the clinicopathological features and differential diagnosis of metanephric adenoma (MA). METHODS: The clinicopathological data of 16 cases with MA diagnosed and treated in Peking University First Hospital from 2004 to 2016 were retrospectively analyzed, and the clinical characteristics, pathologic parameters, differential diagnosis, treatment options and prognosis of MA were analyzed with literature review. RESULTS: The patients included 10 females and 6 males. The age of patients ranged from 14 to 83 years (mean=33.7 years). The partial nephrectomy was carried out for most patients. All cases were located in renal codex with 3 growing into the renal sinus. Histologically, the tumor was composed of tubules, papillary or glomeruloid structures and psammoma bodies were focally seen. Immunohistochemical study showed that all the cases expressed vimentin, and 94% cases expressed CD57, 63% WT1, 75% AE1/AE3, 19% cytokeratin 7 (CK7) and 13%α-methylacyl-CoA racemase (AMACR), and negative expressions for MA included CD10, neuron-specific enolase (NSE) and CD56. Follow-up information from 1 to 125 months was available in all the patients; and none of the patients showed any evidence of recurrence and metastasis. CONCLUSION: The benign tumor characteristics of MA are not obvious for preoperative imaging diagnosis, and the diagnosis of MA should be based on the unique pathological features. Positive immunostain of CD57 is a useful indicator for MA diagnosis and differential diagnosis. The partial nephrectomy surgical treatment can achieve good clinical cure with good prognosis.

Growth and acid production of Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 in the fermentation of algal carcass.

Algal carcass is a low-value byproduct of algae after its conversion to biodiesel. Dried algal carcass is rich in protein, carbohydrate, and multiple amino acids, and it is typically well suited for growth and acid production of lactic acid bacteria. In this study, Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 was used to ferment different algal carcass media (ACM), including 2% ACM, 2% ACM with 1.9% glucose (ACM-G), and 2% ACM with 1.9% glucose and 2g/L amino acid mixture (ACM-GA). Concentrations of organic acids (lactic acid and acetic acid), acetyl-CoA, and ATP were analyzed by HPLC, and activities of lactate dehydrogenase (LDH), acetokinase (ACK), pyruvate kinase (PK), and phosphofructokinase (PFK) were determined by using a chemical approach. The growth of L. bulgaricus cells in ACM-GA was close to that in the control medium (de Man, Rogosa, and Sharpe). Lactic acid and acetic acid contents were greatly reduced when L. bulgaricus cells were grown in ACM compared with the control medium. Acetyl-CoA content varied with organic acid content and was increased in cells grown in different ACM compared with the control medium. The ATP content of L. bulgaricus cells in ACM was reduced compared with that of cells grown in the control medium. Activities of PFK and ACK of L. bulgaricus cells grown in ACM were higher and those of PK and LDH were lower compared with the control. Thus, ACM rich in nutrients may serve as an excellent substrate for growth by lactic acid bacteria, and addition of appropriate amounts of glucose and amino acids can improve growth and acid production.

Effect of the absence of the CcpA gene on growth, metabolic production, and stress tolerance in Lactobacillus delbrueckii ssp. bulgaricus.

The catabolite control protein A (CcpA) is a kind of multi-effect regulatory protein. In the study, the effect of the inactivation of CcpA and aerobic conditions on the growth, metabolic production, and stress tolerance to heat, oxidative, and cold stresses in Lactobacillus delbrueckii ssp. bulgaricus was investigated. Results showed that inactivation of CcpA distinctly hindered growth. Total lactic acid concentration was significantly lower in aerobiosis for both strains and was lower for the mutant strain than L. bulgaricus. Acetic acid production from the mutant strain was higher than L. bulgaricus in aerobiosis compared with anaerobiosis. Enzyme activities, lactate dehydrogenase (LDH), phosphate fructose kinase (PFK), pyruvate kinase (PK), and pyruvic dehydrogenase (PDH), were significantly lower in the mutant strain than L. bulgaricus. The diameters of inhibition zone were 13.59 ± 0.02 mm and 9.76 ± 0.02 mm for L. bulgaricus in anaerobiosis and aerobiosis, respectively; and 8.12 ± 0.02 mm and 7.38 ± 0.02 mm for the mutant in anaerobiosis and aerobiosis, respectively. For both strains, cells grown under aerobic environment possess more stress tolerance. This is the first study in which the CcpA-negative mutant of L. bulgaricus is constructed and the effect of aerobic growth on stress tolerance of L. bulgaricus is evaluated. Although aerobic cultivation does not significantly improve growth, it does improve stress tolerance.

[Clinicopathological features and differential diagnosis of metanephric adenoma: a report of sixteen cases].

OBJECTIVE: To study the clinicopathological features and differential diagnosis of metanephric adenoma (MA). METHODS: The clinicopathological data of 16 cases with MA diagnosed and treated in Peking University First Hospital from 2004 to 2016 were retrospectively analyzed, and the clinical characteristics, pathologic parameters, differential diagnosis, treatment options and prognosis of MA were analyzed with literature review. RESULTS: The patients included 10 females and 6 males. The age of patients ranged from 14 to 83 years (mean=33.7 years). The partial nephrectomy was carried out for most patients. All cases were located in renal codex with 3 growing into the renal sinus. Histologically, the tumor was composed of tubules, papillary or glomeruloid structures and psammoma bodies were focally seen. Immunohistochemical study showed that all the cases expressed vimentin, and 94% cases expressed CD57, 63% WT1, 75% AE1/AE3, 19% cytokeratin 7 (CK7) and 13%α-methylacyl-CoA racemase (AMACR), and negative expressions for MA included CD10, neuron-specific enolase (NSE) and CD56. Follow-up information from 1 to 125 months was available in all the patients; and none of the patients showed any evidence of recurrence and metastasis. CONCLUSION: The benign tumor characteristics of MA are not obvious for preoperative imaging diagnosis, and the diagnosis of MA should be based on the unique pathological features. Positive immunostain of CD57 is a useful indicator for MA diagnosis and differential diagnosis. The partial nephrectomy surgical treatment can achieve good clinical cure with good prognosis.

CD4+Foxp3+ regulatory T cell differentiation mediated by endometrial stromal cell-derived TECK promotes the growth and invasion of endometriotic lesions.

Endometriosis is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissue. The proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) is significantly increased in the peritoneal fluid of women with endometriosis. The thymus-expressed chemokine TECK/CCL25 directly promotes the invasiveness of endometrial stromal cells (ESCs). The aim of this study was to investigate the effects of ESC-derived TECK on the crosstalk between Tregs and ESCs in the progress of endometriosis. We determined that the percentage of Tregs and the concentration of TECK increased in the peritoneal fluid with the progression of endometriosis. The supernatant from co-cultured human ESCs and macrophages not only induced Treg differentiation and increased Treg expression of interleukin-10 (IL-10), transforming growth factor-ß (TGF-ß) and CD73 by activating the AKT/STAT3 signaling pathway but also repressed Treg apoptosis by downregulating Fas and FasL expression and enhanced the Treg-mediated suppression of CD4(+)CD25(-) T cells. In addition, in vitro and in vivo trials confirmed that these effects could be inhibited by anti-TECK neutralizing Abs. The secretion of IL-10 and TGF-ß by Tregs increased MMP2 expression and decreased TIMP1 expression and further stimulated the proliferation and invasion of ESCs and the growth of ectopic lesions. These results indicate that TECK derived from ESCs and macrophages upregulates the number and function of Tregs in the ectopic milieu, which contributes to endometriotic immunotolerance and high levels of ESC proliferation and invasion, thereby facilitating the progression of endometriosis.

High-efficiency combinatorial approach as an effective tool for accelerating metallic biomaterials research and discovery.

A high-efficiency combinatorial approach has been applied to rapidly build the database of composition-dependent elastic modulus and hardness of the Ti-Ta and Ti-Zr-Ta systems. A diffusion multiple of the Ti-Zr-Ta system was manufactured, then annealed at 1173K for 1800h, and water quenched to room temperature. Extensive interdiffusion among Ti, Zr and Ta has taken place. Combining nanoindentation and electron probe micro-analysis (EPMA), the elastic modulus, hardness as well as composition across the diffusion multiple were determined. The composition/elastic modulus/hardness relationship of the Ti-Ta and Ti-Zr-Ta alloys has been obtained. It was found that the elastic modulus and hardness depend strongly on the Ta and Zr content. The result can be used to accelerate the discovery/development of bio-titanium alloys for different components in implant prosthesis.

RANKL promotes the growth of decidual stromal cells in an autocrine manner via CCL2/CCR2 interaction in human early pregnancy.

OBJECTIVE: Receptor-activator of NF-κB ligand (TNFSF11, also known as RANKL) and its receptor RANK are essential regulators on bone remodeling, mammary gland development and hormone-associated breast cancer development. However, the expression pattern and role of RANKL/RANK axis in decidual stromal cells (DSCs) are unclear in human early pregnancy. STUDY DESIGN: We analyzed RANKL/RANK expression in DSCs by real-time PCR, immunhistochemistry, enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Then BrdU cell proliferation assay, flow cytometry assay and ELISA were performed to investigate the effect of recombinant human RANKL and DSCs-derived RANKL on the proliferation, apoptosis, chemokine (C-C motif) ligand 2 (CCL2) secretion, C-C chemokine receptor type 2 (CCR2) and other target proteins expression in DSCs in vitro, respectively. RESULTS: Here we show that DSCs co-express RANKL/RANK. Not only recombinant human (rh) RANKL but also the DSC-secreted RANKL stimulate proliferation and anti-apoptosis, and elevate CCL2 secretion and CCR2 expression of DSCs. Furthermore, the stimulatory effects on the proliferation, anti-apoptosis and the expression of Bcl-2 and Ki67 and inhibitory signaling on Fas ligand (FasL) in DSCs induced by RANKL can be partly reversed by the way of blocking CCL2 and or CCR2. CONCLUSIONS: Our results have revealed that RANKL/RANK signal promotes Bcl-2 and Ki67 and decreases FasL expression, and further as a positive regulator for stimulating the proliferation and growth of DSCs through up-regulating CCL2/CCR2 signal, which finally contributes to the establishment and maintenance of physiological pregnancy.