Human embryonic stem (hES) cells are pluripotent cell lines established from the explanted inner cell mass of human blastocysts. Despite their importance for human embryology and regenerative medicine, studies on hES cells, unlike those on mouse ES (mES) cells, have been hampered by difficulties in culture and by scant knowledge concerning the regulatory mechanism. Recent evidence from plants and animals indicates small RNAs of approximately 22 nucleotides (nt), collectively named microRNAs, play important roles in developmental regulation. Here we describe 36 miRNAs (from 32 stem-loops) identified by cDNA cloning in hES cells. Importantly, most of the newly cloned miRNAs are specifically expressed in hES cells and downregulated during development into embryoid bodies (EBs), while miRNAs previously reported from other human cell types are poorly expressed in hES cells. We further show that some of the ES-specific miRNA genes are highly related to each other, organized as clusters, and transcribed as polycistronic primary transcripts. These miRNA gene families have murine homologues that have similar genomic organizations and expression patterns, suggesting that they may operate key regulatory networks conserved in mammalian pluripotent stem cells. The newly identified hES-specific miRNAs may also serve as molecular markers for the early embryonic stage and for undifferentiated hES cells.
Functional polymeric films with antireflective and hydrophobic properties have been widely used for electronic device displays. However, the design of such functional films with an antimicrobial characteristic has been a challenge. We designed a nanostructured surface using a rigorous coupled-wave analysis to obtain a period of 300 nm and an aspect ratio of 3.0 on a flat poly(methyl methacrylate) film. The fabricated nanostructure was hydrophobic and exhibited the desired optical characteristics with a reflectance of less than 0.5% over the visible wavelength range. Furthermore, the nanoimprinted polymer film exhibited antimicrobial characteristics and low adhesion when compared with the corresponding flat surface. The results suggest that the nanostructured surface designed in this study is multifunctional and should be suitable for the production of protective optical and hygienic polymer films for the displays of portable electronic devices.
ObjectiveTo test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.MethodsIn this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.ResultsA total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range, 28–83) years, and mean interval between stroke onset to randomization was 20.2 (range, 5–89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious, treatment-related adverse events.ConclusionsIntravenous application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.Classification of evidenceThis study provides Class III evidence that autologous mesenchymal stem cells do not improve 90-day outcomes in patients with chronic stroke.Trial registrationclinicaltrials.gov Identifier: NCT01716481.
The intrathecal administration of p38 MAP kinase (p38) inhibitor has been shown to reduce hyperalgesia. In the present study, we investigated the activation of p38 in the rat dorsal root ganglion (DRG) and spinal cord following peripheral tissue inflammation and nerve injury immunohistochemically. Peripheral inflammation and chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the percentage of phosphorylated (P-) p38-immunoreactive (IR) neurons, primarily small sized ones in bilateral DRGs. In contrast, following axotomy, a significant decrease in the percentage of IR neurons was observed in ipsilateral DRGs. In addition, a marked increase was observed in the number of P-p38-IR microglia in the ipsilateral laminae I-IV and IX of the spinal cord following peripheral inflammation, CCI or axotomy. These findings suggest that p38 may play an important role in hyperalgesia and the activation of the spinal microglia.
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