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BACKGROUND Mesenchymal stem cells (MSCs) are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory properties. Although human bone marrow-derived MSCs (BM-MSCs) were the most widely used MSCs in cell therapy until recently, MSCs derived from human umbilical cords (UC-MSCs) have gained popularity as cell therapy material for their ethical and noninvasive collection. AIM To investigate the difference in mechanisms of the immunosuppressive effects of UC-MSCs and BM-MSCs. METHODS To analyze soluble factors expressed by MSCs, such as indolamine 2,3-dioxygenase, cyclooxygenase-2, prostaglandin E2 and interleukin (IL)-6, inflammatory environments in vitro were reconstituted with combinations of interferon-gamma (IFN-γ), tumor necrosis factor alpha and IL-1β or with IFN-γ alone. Activated T cells were cocultured with MSCs treated with indomethacin and/or anti-IL-10. To assess the ability of MSCs to inhibit T helper 17 cells and induce regulatory T cells, induced T helper 17 cells were cocultured with MSCs treated with indomethacin or anti-IL-10. Xenogeneic graft-versus-host disease was induced in NOG mice (NOD/Shi-scid/IL-2Rγnull) and UC-MSCs or BM-MSCs were treated as cell therapies. RESULTS Our data demonstrated that BM-MSCs and UC-MSCs shared similar phenotypic characteristics and immunomodulation abilities. BM-MSCs expressed more indolamine 2,3-dioxygenase after cytokine stimulation with different combinations of IFN-γ, tumor necrosis factor alpha-α and IL-1β or IFN-γ alone. UC-MSCs expressed more prostaglandin E2, IL-6, programmed death-ligand 1 and 2 in the in vitro inflammatory environment. Cyclooxygenase-2 and IL-10 were key factors in the immunomodulatory mechanisms of both MSCs. In addition, UC-MSCs inhibited more T helper 17 cells and induced more regulatory T cells than BM-MSCs. UC-MSCs and BM-MSCs exhibited similar effects on attenuating graft-versus-host disease. CONCLUSION UC-MSCs and BM-MSCs exert similar immunosuppressive effects with different mechanisms involved. These findings suggest that UC-MSCs have distinct immunoregulatory functions and may substitute BM-MBSCs in the field of cell therapy.

Objective To examine the features and efficacy of transthoracic echocardiography (TTE) in preeclampsia. Methods We retrospectively reviewed the medical records of 145 pregnant women with preeclampsia, who underwent TTE at Seoul St. Mary’s Hospital between July 2006 and June 2016. We analyzed echocardiographic features in preeclampsia and the relationship between the severity of preeclampsia and TTE findings. Additionally, we examined the predictive echocardiographic factors of persistent hypertension and calculated the adjusted odds ratio (OR) and 95% confidence interval (CI) for multiple regression models by considering systolic and diastolic blood pressure and pre-pregnancy body mass index (BMI). Results Hemodynamic findings assessed by TTE in women with preeclampsia included systolic and diastolic dysfunction, increased left ventricular mass, and enlarged left atrium. Diastolic dysfunction and left ventricular hypertrophy (LVH) were more common in preeclampsia with severe features (39.84% vs. 32.05%, p = 0.010, and 21.79% vs. 8.96%, p = 0.041, respectively). In the patients with systolic dysfunction, the adjusted OR for persistent hypertension was 17.41 (95% CI = 2.83–107.20). The ORs for grade 1 and grade 2 diastolic dysfunction were 12.58 and 32.84, respectively (95% CI, 2.99–52.92 and 3.61–298.58, respectively). When LVH assessed by TTE was considered with diastolic dysfunction, the risk for persistent hypertension increased (OR 19.28; 95% CI − 4.36–85.20). Conclusion TTE not only can reveal the severity of preeclampsia, but also can be a useful tool for the follow-up of persistent hypertension.

Objective To evaluate the relationships between sociodemographic factors, reproductive history, and subsequent risk of osteoarthritis (OA) or pain of the hip, knee, and back in Korean women. Materials and Methods This study included data of 5101 women aged over 50 years, taken from the Korean National Health and Nutritional Examination Survey V from 2010 to 2012. Women were stratified according to parity, as well as delivery mode. Multivariate logistic regression analysis was conducted to evaluate relationships between radiographic OA or symptomatically possible OA (back, knee, or hip), and historical factors. Results Vaginal delivery was associated with an increased risk of symptomatic back OA [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.062, 2.881] but was not associated with symptomatic knee and hip OA in adjusted analysis. Radiographically, vaginal delivery was not associated with risks of back and knee OA, but was negatively associated with hip OA (OR 0.184, 95% CI 0.039, 0.863), compared to cesarean delivery. High parity (over 5) was associated with radiographic knee OA (OR 1.328, 95% CI 1.006, 1.754) in adjusted analysis. High parity (over 3) was associated with symptomatic back OA. Conclusion Parity was associated with higher risk of radiographic knee OA. Vaginal delivery was positively associated with symptomatic back OA, but negatively associated with radiographic knee OA. Further study is required to evaluate the mechanism between delivery mode and subsequent OA.

The interpretation of the fetal heart rate (FHR) signal considering labor progression may improve perinatal morbidity and mortality. However, there have been few studies that evaluate the fetus in each labor stage quantitatively.To evaluate whether the entropy indices of FHR are different according to labor progression.A retrospective comparative study of FHR recordings in three groups: 280 recordings in the second stage of labor before vaginal delivery, 31 recordings in the first stage of labor before emergency cesarean delivery, and 23 recordings in the pre-labor before elective cesarean delivery.The stored FHR recordings of external cardiotocography during labor.Approximate entropy (ApEn) and sample entropy (SampEn) for the final 2000 RR intervals.The median ApEn and SampEn for the 2000 RR intervals showed the lowest values in the second stage of labor, followed by the emergency cesarean group and the elective cesarean group for all time segments (all P0.001). Also, in the second stage of labor, the final 5 min of 2000 RR intervals had a significantly lower median ApEn (0.49 vs. 0.44, P=0.001) and lower median SampEn (0.34 vs. 0.29, P0.001) than the initial 5 min of 2000 RR intervals.Entropy indices of FHR were significantly different according to labor progression. This result supports the necessity of considering labor progression when developing intrapartum fetal monitoring using the entropy indices of FHR.

Mesenchymal stromal/stem cells derived from human Wharton's jelly (WJ-MSC) have emerged as a favorable source for autologous and allogenic cell therapy. Here, we characterized the proangiogenic features of WJ-MSCs and examined their ability to form functional vessels in in vivo models. First, we examined whether WJ-MSCs express endothelial and smooth muscle cell specific markers after culture in endothelial growth media. WJ-MSCs expressed an endothelial specific marker, VEGFR1, at mRNA and protein levels, but did not express other specific markers (VEGFR2, Tie2, vWF, CD31, and VE-cadherin). Rather, WJ-MSCs expressed smooth muscle cell specific markers, α-SMA, PDGFR-β and calponin, and were unable to form tube-like structures with lumen on Matrigel. WJ-MSCs secreted growth factors including angiogenin, IGFBP-3, MCP-1, and IL-8, which stimulated endothelial proliferation, migration, and tube formation. When WJ-MSCs suspended in Matrigel were implanted into nude mice, it led to formation of functional vessels containing erythrocytes after 7 days. However, implantation of endothelial cell-suspended Matrigel resulted in no perfused vessels. The implanted WJ-MSCs were stained positively for calponin or PDGFR-β and were located adjacent to the lining of mouse endothelial cells that were stained with labeled BS-lectin B4. In a murine hindlimb ischemia model, the transplantation of MSCs (5 × 10 5 cells) into the ischemic limbs improved perfusion recovery and neovascularization of the limbs compared to control group. Therefore, the results suggest that WJ-MSCs promote neovascularization and perfusion by secreting paracrine factors and by functioning as perivascular precursor cells, and that WJ-MSCs can be used efficiently for cell therapy of ischemic disease.

Spectral analysis of fetal heart rate (FHR) variability is a useful method to assess fetal condition. There have been several studies involving the change in spectral power related to fetal acidemia, but the results have been inconsistent.To determine the change in spectral power related to fetal umbilical arterial pH at birth, dividing cases into preterm (31-36 weeks) and term (≥37 weeks) gestations.Case-control study. The 514 cases of deliveries were divided into a low-pH group (an umbilical arterial pH7.2) and a control group (pH≥7.2).FHR recorded on cardiotocography during the last 2h of labor.The spectral powers in various bands of FHR variability.In preterm fetuses, the total, low (LF), and movement (MF) frequency spectral powers and LF/HF ratio were significantly lower in the low-pH group than the control group (all P0.05). In contrast, in term fetuses, the total frequency, LF, and MF powers were significantly higher in the low-pH group than the control group (all P0.05). The area under the receiver operating characteristic of LF power to detect a low pH at birth was 0.794 in preterm fetuses and 0.595 in term fetuses. The specificity was 86.8% and 93.3% in preterm and term fetuses, respectively.The changes in spectral power responding to a low pH are different between term and preterm fetuses. Spectral analysis of FHR variability may be useful fetal monitoring for early detection of fetal acidemia.

Circulating endothelial progenitor cells (EPCs) contribute to neovascularization in tumor or ischemic tissues by multi-step events, including adhesion, migration, chemoattraction, and differentiation to endothelial cells. Anti-angiogenic RGD-peptides have been shown to directly induce apoptosis in human umbilical vein endothelial cells (HUVECs) and T cells. Here, we examined the effects of RGD-peptides on EPCs in terms of adhesive differentiation and apoptosis. When mononuclear cells (MNCs) isolated from human cord blood were cultured on fibronectin-coated plates for 7 days, RGD-peptide treatment decreased dose-dependently the number of adherent cells double positive for DiI-ac-LDL uptake and UEA-1 binding. The cells treated with RGD peptide were also stained less strongly by vWF or KDR antibody by immunofluorescence staining. Immobilization of the RGD-peptide promoted cell adhesion, but resulted in a deficiency in the development of ability of ac-LDL uptake and UEA-1 binding, showing an antagonistic effect. Accordingly, ex vivo-cultivated EPCs expressed integrin alpha5, alphav, beta1, beta3, and beta5, and antibodies to integrins alpha5, alphav, and beta1 decreased the number of adherent cells. However, viability of total MNCs containing early EPCs was not affected by RGD-peptide. In addition, neither an increase in apoptotic cell death nor a direct activation of caspase-3 by RGD-peptide was detected in ex vivo-cultivated EPCs, unlike in HUVECs. Interestingly, RGD-peptide rather enhanced Bcl-2 expression in ex vivo-cultivated EPCs and the EPCs themselves with a high Bcl-2/Bax ratio are comparatively resistant to apoptosis. Therefore, these results suggest that RGD-peptides may inhibit EPC differentiation by anti-adhesive effect, but not by a direct pro-apoptotic effect.

Objective To know the effect of adenosine 5′-triphosphate (ATP) on intracellular calcium level and cell proliferation in cervical cancer cells. Study design Four different human cervical cancer cell lines (Caski, C33A, HeLaS3 and SiHa) were used in this study. The change of intracellular calcium level, cell proliferation and the activity of proliferation- and calcium-related transcription factors by extracellular ATP were examined in these cell lines. Results Extracellular ATP induced calcium mobilization, cell proliferation and the activation of NF-κB in all cell lines used. Conclusion These results suggest that calcium mobilization and NF-κB dependent signaling pathway play an important role in the cell proliferation by ATP in cervical cancer.

Three proteases were identified in the excretory/secretory proteins (ESP) from Toxoplasma gondii by the gelatin acrylamide gel electrophoresis (GAGE), of which the molecular masses were 80, 70, and 42 kDa. One of the proteases with 42 kDa was reactive to a monoclonal antibody (mAb), Tg786 clone, which was localized in the rhoptry of T. gondii by immunohistochemistry. The protease was maximally active at the pH range between 7.5 and 8.5, and was sensitive to inhibition by TPCK and EGTA. The gelatinolytic activity of the protease was dependent on the concentration of calcium ion. The protease was active only in the millimolar ranges of calcium but not in micromolar ranges, implicating that the secretion is critical event for the activation of the protease. The secreted protease was shown to bind to the host cells upon Western blot and immunofluorescence analysis. It is suggested that the protease may target to the plasma membrane of the host cells, which provides appropriate environment for the entry of the parasite into host cells. The mAb (Tg786) of T. gondii also reacted with a protein of the same size and equivalent locality of rhoptry in Neospora caninum, a similar Apicomplexan protozoa, suggesting that secreted protease mediates a common function in the mechanism of entry into host cells.

OBJECTIVE: 1) To examine trends in black-white disparities in infant deaths due to congenital anomalies in the United States, and 2) To explore whether state funding of pregnancy termination for women on Medicaid is associated with rates of infant death due to anomalies. STUDY DESIGN: We used US vital statistics records from 1983-2004. Data on state funding of pregnancy termination under Medicaid was obtained from the Guttmacher Institute. Poisson regression was used to examine rates of infant death due to congenital anomalies by race and year, adjusting for maternal age. Trends in racial disparities were examined by including an interaction term between year and race, then calculating adjusted risk differences (RD) and rate ratios (IRR) at various years. The association between state Medicaid coverage of pregnancy termination for fetal indications and mortality rates in recent years (2001-2004) was examined using a Poisson model. RESULTS: Infant deaths due to anomalies decreased by 3% per year between 1983 and 2004, from 257 to 136 per 100,000 live births. During this time, the gap between blacks and whites widened steadily (Figure). In 1983, the adjusted RD was 20.5 per 100,000 (95% CI [13.8, 27.2], IRR1⁄41.08 [1.06, 1.11]); by 2004, this had grown to 36.2 per 100,000 ([31.5, 40.9], IRR1⁄41.27 [1.24, 1.31]). Black women were more likely to live in states without Medicaid coverage of pregnancy termination (68 vs 59%) and these states had higher rates of infant death due to anomalies (22.0/100,000 higher [15.4, 28.5], IRR1⁄41.19 [1.16, 1.23]). CONCLUSION: Infant deaths due to anomalies are more common among blacks than whites, and this disparity has increased steadily over time. Rates are higher when pregnancy termination for fetal indications is not covered under Medicaid. There is a need to better understand whether differences in access to, or uptake of, pregnancy termination of anomalous fetuses has contributed to the growing black-white gap in infant deaths due to anomalies.