Exosomes Secreted by Wharton's Jelly-Derived Mesenchymal Stem Cells Promote the Ability of Cell Proliferation and Migration for Keratinocyte.

Mesenchymal stem cells (MSCs) isolated from Wharton's jelly (WJ-MSCs) and adipose tissue (AD-MSCs) are alternative sources for bone marrow-derived MSCs. Owing to their multiple functions in angiogenesis, immune modulation, proliferation, migration, and nerve regeneration, MSC-derived exosomes can be applied in "cell-free cell therapy". Here, we investigated the functional protein components between the exosomes from WJ-MSCs and AD-MSCs to explain their distinct functions. Proteins of WJ-MSC and AD-MSC exosomes were collected and compared based on iTRAQ gel-free proteomics data. Results: In total, 1695 proteins were detected in exosomes. Of these, 315 were more abundant (>1.25-fold) in AD-MSC exosomes and 362 kept higher levels in WJ-MSC exosomes, including fibrinogen proteins. Pathway enrichment analysis suggested that WJ-MSC exosomes had higher potential for wound healing than AD-MSC exosomes. Therefore, we treated keratinocyte cells with exosomes and the recombinant protein of fibrinogen beta chain (FGB). It turned out that WJ-MSC exosomes better promoted keratinocyte growth and migration than AD-MSC exosomes. In addition, FGB treatment had similar results to WJ-MSC exosomes. The fact that WJ-MSC exosomes promoted keratinocyte growth and migration better than AD-MSC exosomes can be explained by their higher FGB abundance. Exploring the various components of AD-MSC and WJ-MSC exosomes can aid in their different clinical applications.

Profile of Urinary Cytokines in Kawasaki Disease: Non-Invasive Markers.

This cohort study aimed to investigate urinary cytokines expression to help identify a less invasive method of cytokine detection for Kawasaki disease (KD). Patients with confirmed KD were recruited. Patients with fever or urinary tract infection (UTI) were enrolled as control groups. Urinary samples were collected before and 3 days after intravenous immunoglobulin (IVIG) treatment. The levels of cytokines were detected by MILLPLEX® MAP human multiplex assay. All cytokines, i.e., epidermal growth factor (EGF), interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-13, IL-17A, IL-33, interferon-gamma-induced protein (IP)-10, macrophage inflammatory protein (MIP)-1ß, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) except monocyte chemoattractant protein (MCP)-1 were significantly higher in the KD group, compared with the fever-control (FC) group, whereas the expressions of IFN-γ, IL-1ß, IL-6, IL-8, IL-17A, IL-33, MCP-1, MIP-1ß, and TNF-α were significantly lower in the urine of KD patients, as compared with the UTI group. The expressions of EGF, IFN-γ, IL-8, IL-13, and IL-17A were higher in the urine of KD patients than in the FC group, whereas the level of IL-1ß was lower in KD than in the UTI group after age adjustment by logistic regression. Levels of IL-6, IL-8, IL-13, IP-10, and MCP-1 were significantly higher in the pre-IVIG urine of KD patients than in the post-IVIG treatment group. Additionally, urine IL-4 and blood C-reactive protein were higher in the KD group with coronary artery lesion (CAL) than in the non-CAL group. Results of this study provide a new view of urinary cytokine expression in the disease progress of KD, which may help clinicians to predict and prevent morbidity early and non-invasively.

Salivary cytokine - A non-invasive predictor for bronchopulmonary dysplasia in premature neonates.

BACKGROUND: To find a less invasive method of cytokine detection for premature neonates, we conducted this cohort study to investigate the salivary cytokines and to analyze their correlations with bronchopulmonary dysplasia (BPD). METHODS: Premature neonates younger than 34 weeks of gestational age without maternal or neonatal infection were recruited. Salivary samples were collected on their first (D1) and seventh (D7) days of life. The cytokine levels were detected by MILLPLEX® MAP Human multiplex assay. One-way analysis of variance, the Kruskal-Wallis test, Pearson's chi-square test, and logistic regression were used to analyze the data. RESULTS: Totally 125 neonates were enrolled and separated into four groups: control, mild, moderate, and severe BPD group. The salivary levels of D1 interleukin (IL)-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, and D7 IL-6 (p = 0.001, 0.001, 0.000, 0.043, 0.037 and 0.001, respectively) were significantly higher in the BPD groups than in the control group. After adjusting for the gestational age, acid-base equivalent, and absolute neutrophil count, comparing to the control group, the levels of D7 IL-17 became significantly lower in all three BPD groups (p = 0.032, 0.030, and 0.030, respectively) and that of D7 IFN-α2 became significantly lower in the severe BPD group (p = 0.037). CONCLUSION: Early-life salivary cytokine levels were correlated with the development of BPD in premature neonates. This study provides a novel method to predict BPD early and non-invasively.

A novel method to detect bacterial infection in premature infants: Using a combination of inflammatory markers in blood and saliva.

BACKGROUND: Opportunistic infection leads to high morbidity and mortality in premature babies due to their immature immune system. Biomarkers in blood have been reported to detect bacterial infection in neonates. However, serial blood exams pose iatrogenic anemia in premature babies. Thus, this study aimed to identify cytokines in saliva, which can help to diagnose bacterial infection in premature babies via a non-invasive method. METHODS: Premature neonates were enrolled from Aug. 2012 to Feb. 2015 after completing informed consent. Babies with congenital anomalies, bronchopulmonary dysplasia, necrotizing enterocolitis and any surgical indicated diseases were excluded. Salivary samples collection and septic work-up were performed when bacterial infection was clinically suspected, as well as one week after antimicrobial treatment. The level of salivary cytokines was detected by MILLPLEX® MAP and analyzed by Mann-Whitney U test. RESULTS: There were 16 episodes of bacterial infection in 10 cases. Culture-positive group had significantly higher levels of salivary Interleukin (IL) 6, IL-8, macrophage inflammatory protein (MIP)1α, MIP-1ß and tumor necrosis factor (TNF)-α than that in the culture-negative group (p = 0.002, 0.006, 0.001, <0.001, 0.009), and blood C-reactive protein and sugar as well (p < 0.001, 0.026). After adjusting postmenstrual age by logistic regression, blood sugar level was the most significant biomarker (p = 0.019). In combination of blood and salivary biomarkers, blood sugar higher than 67 mg/dL and salivary IL-6 higher than 367.25 pg/mL concurrently, would accurately detect bacterial infection in premature babies. CONCLUSION: This non-invasive method might help us to accurately diagnose bacterial infection in premature babies.

MicroRNA-142-3p and let-7g Negatively Regulates Augmented IL-6 Production in Neonatal Polymorphonuclear Leukocytes.

Neonatal PMN are qualitatively impaired in functions, yet they frequently reveal augmented inflammatory reactions during sepsis. Here, we hypothesized that PMN from newborns produce more IL-6 than those from adults under LPS stimulation, in which transcriptional or posttranscriptional regulation is involved in the altered expression. We found that neonatal PMN produced significantly higher IL-6 mRNA and protein than adult PMN. The higher IL-6 expression was not related to transcriptional but posttranscriptional regulation as the IL-6 expression was affected by the addition of cycloheximide but not actinomycin. To examine whether miRNA was involved in the IL-6 regulation of neonatal PMN, we surveyed differential displays of miRNAs that could potentially regulate IL-6 expression before and after LPS stimulation. Four miRNAs: hsa-miR-26a, hsa-miR-26b, hsa-miR-142-3p and hsa-let 7g decreased or increased after LPS treatment for 4 h. Further validation by qRT-PCR identified miR-26b, miR-142-3p and let-7g significantly changed in neonatal PMN after LPS stimulation. The functional verification by transfection of miR-142-3p and let-7g precursors into neonatal PMN significantly repressed the IL-6 mRNA and protein expression, suggesting that miR-142-3p and let-7g negatively regulate IL-6 expression in neonatal PMN. Modulation of miRNA expression may be used to regulate IL-6 production in newborns with altered inflammatory reactions.

Urachal catheter provides new choice for long-term urinary diversion in prune belly syndrome.

Prune belly syndrome has been identified as a clinical triad of abdominal muscle deficiency, bilateral cryptorchidism, and urologic abnormalities. We present the case of a discordant monozygotic twin with prune belly syndrome and voiding dysfunction that was relieved by long-term urinary catheterization by way of the urachus. To the best of our knowledge, this alternative method has not been previously reported. We suggest that for newborn infants with long-term voiding dysfunction, if the urachus retains patency, urinary catheterization through the urachus could be a choice for urine drainage instead of cystostomy, providing a better cosmetic appearance and quality of life.

Treatment with high-dose methylprednisolone for hepatic veno-occlusive disease in a child with rhabdomyosarcoma.

Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome, is rapidly progressing and involves life-threatening complications that can occur in patients receiving chemotherapy and/or bone marrow transplantation. No completely satisfactory treatmentstrategies have yet been established. We present a case of rhabdomyosarcoma ina 21-month-old boy who developed pancytopenia, dyspnea, jaundice, massive ascites and body weight gain of more than 10% after receiving conventional chemotherapy. Hepatic VOD was diagnosed. He recovered after supportive care and treatment with high-dose methylprednisolone.