Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cordderived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:725-731

ObjectivesRecent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis.MethodsMouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets.ResultsCdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7a overexpression. The SP1 was identified as a new miR-7a target, in line with previously identified PARP, while miR-7a-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7a overexpression reversed these changes.ConclusionsCdr1as also functioned as a powerful miR-7a sponge in myocardial cells, and showed regulation on the protective role of miR-7a in MI injury, involving the function of miR-7a targets, PARP and SP1.

Background:The aim of this meta-analysis was to investigate the prenatal, perinatal, and postnatal risk factors for children autism.Methods:PubMed, Embase, Web of Science were used to search for studies that examined the prenatal, perinatal, and postnatal risk factors for children autism. A fixed-effects model or random-effects model was used to pool the overall effect estimates.Results:Data from 37,634 autistic children and 12,081,416 nonautistic children enrolled in 17 studies were collated. During the prenatal period, the factors associated with autism risk were maternal and paternal age≥35 years, mother's and father's race: White and Asian, gestational hypertension, gestational diabetes, maternal and paternal education college graduate+, threatened abortion, and antepartum hemorrhage. During perinatal period, the factors associated with autism risk were caesarian delivery, gestational age≤36 weeks, parity≥4, spontaneous labor, induced labor, no labor, breech presentation, preeclampsia, and fetal distress. During the postnatal period, the factors associated with autism risk were low birth weight, postpartum hemorrhage, male gender, and brain anomaly. Parity≥4 and female were associated with a decreased risk of autism. In addition, exposure to cigarette smoking, urinary infection, mother's and father's race: Black and Hispanic, mother's country of birth outside Europe and North America, umbilical cord around neck, premature membrane rupture, 5-minutes Apgar score<7, and respiratory infection were not associated with increased risk of autism.Conclusion:The present meta-analysis confirmed the relation between some prenatal, perinatal, and postnatal factors with autism. All these factors were examined individually, thus it was still unclear that whether these factors are causal or play a secondary role in the development of autism. Further studies are needed to verify our findings, and investigate the effects of multiple factors on autism, rather than the single factor.

Graphene oxide has attracted widespread attention in the biomedical fields due to its excellent biocompatibility. Herein we investigated the layer-number dependent antibacterial and osteogenic behaviors of graphene oxide in biointerfaces. Graphene oxide with different layer numbers was deposited on the titanium surfaces by cathodal electrophoretic deposition with varied deposition voltages. The initial cell adhesion and spreading, cell proliferation, and osteogenic differentiation were observed from all the samples using rat bone mesenchymal stem cells. Both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus were used to investigate the antibacterial effect of the modified titanium surfaces. Cocultures of human gingival fibroblasts (HGF) cells with Escherichia coli and Staphylococcus aureus were conducted to simulate the conditions of the clinical practice. The results show that the titanium surfaces with graphene oxide exhibited excellent antibacterial and osteogenic effects. Increasing the layer-number of graphene oxide resulted in the augment of reactive oxygen species levels and the wrinkling, which led to the antibacterial and osteogenic effects, respectively. Compared to pure titanium surface in the cells-bacteria coculture process, the modified titanium surfaces with graphene oxide exhibited higher surface coverage percentage of cells.

MiR-21-5p showed the most specific expression patterns in all patients with subclinical hypothyroidism (SCH and SCH+ATH groups). Down-regulation of miR-125a-5p, miR-126-3p, miR-221-3p, and miR-222-3p may be a manifestation of atherosclerosis either in SCH+ATH or in ATH-alone patients. MiR-126-3p has the most specific expression patterns in all atherosclerosis patients (SCH+ATH and ATH groups).

From the perspective of surface modification of biomaterials, graphene is very promising because of its unique physical and chemical properties. Herein, we report direct in situ fabrication of graphene on nitinol (NiTi) shape memory alloy by chemical vapor deposition (CVD) and investigate both the growth mechanism as well as surface bioactivity of the modified alloy. Growth of the graphene layer is independent of Ni but is rather correlated with the formation of the TiC phase on the surface. Graphene nucleates and grows on this carbide layer during exposure to CH4. The graphene layer is observed to promote the osteogenesis differentiation of mesenchymal stem cells and surface bioactivity. The use of graphene as a bioactive layer is a viable approach to improving the surface properties of NiTi-based dental and orthopedic implants and components.

The emergence of drug-resistant bacteria severely challenges the antimicrobial agents and antibacterial strategy. Here, we demonstrate a novel, simple, and highly efficient combination therapy strategy by direct combinations of cationic conjugated polymers (CCPs) with polypeptide antibiotics against Gram-negative and Gram-positive bacteria based on a synergistic antibacterial effect. The combination therapy method enhances the antibacterial efficacy with a significantly reduced antibiotic dosage. Also, the highly efficient and synergistic killing of drug-resistant bacteria is realized. Using combinations of CCPs and antibiotics to show increased antibacterial activity, this strategy will provide a much wider scope of the discovery of efficient antibacterial systems than that of antibiotic-antibiotic combinations. The proposed combination therapy method provides a universal and powerful platform for the treatment of pathogens, in particular, the drug-resistant bacteria, and also opens a new way for the development of efficient antibacterial systems.