Mesenchymal stem cells (MSCs) have been the focus of an emerging treatment for osteoarthritis. However, few studies reported about outcomes of an intra‐articular injection of autologous adipose‐derived mesenchymal stem cells (AD‐MSCs). This study aimed to assess the efficacy and safety of a single intra‐articular injection of AD‐MSCs for patients with knee osteoarthritis. It was a prospective double‐blinded, randomized controlled, phase IIb clinical trial. AD‐MSCs were administered for 12 patients (MSC group), and the group was compared with 12 knees with injection of normal saline (control group) up to 6 months. All procedures were performed in the outpatient clinic. Primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score. Secondary outcome measure included various clinical and radiologic examination, and safety after injection. Change of cartilage defect after injection was evaluated using magnetic resonance imaging (MRI). Single injection of AD‐MSCs led to a significant improvement of the WOMAC score at 6 months. In the control group, there was no significant change in the WOMAC score at 6 months. No serious adverse events were observed in both groups during the follow‐up period. In MRI, there was no significant change of cartilage defect at 6 months in MSC group whereas the defect in the control group was increased. An intra‐articular injection of autologous AD‐MSCs provided satisfactory functional improvement and pain relief for patients with knee osteoarthritis in the outpatient setting, without causing adverse events at 6 months' follow‐up. Larger sample size and long‐term follow‐up are required. stem cells translational medicine 2019;8:504–511

One of the major factors governing the "top-down" sequence analysis of intact multiply protonated proteins by tandem mass spectrometry is the effect of the precursor ion charge state on the formation of product ions. To more fully understand this effect, electrospray ionization coupled to a quadrupole ion trap mass spectrometer, collision-induced dissociation, and gas-phase ion/ion reactions have been employed to examine the fragmentation of the [M + 12H]12+ to [M + H]+ ions of bovine ubiquitin. At low charge states (+1 to +6), loss of NH3 or H2O from the protonated precursor and directed cleavage at aspartic acid residues was observed. At intermediate charge states, (+7, +8, and +9), extensive nonspecific fragmentation of the protein backbone was observed, with 50% sequence coverage obtained from the [M + 8H]8+ ion alone. At high charge states, (+10, +11, +12), the single dominant channel that was observed was the preferential fragmentation of a single proline residue. These data can be readily explained in terms of the current model for intramolecular proton mobilization, that is, the "mobile proton model", the mechanisms for amide bond dissociation developed for protonated peptides, as well as the structures of the multiply charged ions of ubiquitin in the gas phase, examined by ion mobility and hydrogen/deuterium exchange measurements.

The shift from terrestrial to aquatic life by whales was a substantial evolutionary event. Here we report the whole-genome sequencing and de novo assembly of the minke whale genome, as well as the whole-genome sequences of three minke whales, a fin whale, a bottlenose dolphin and a finless porpoise. Our comparative genomic analysis identified an expansion in the whale lineage of gene families associated with stress-responsive proteins and anaerobic metabolism, whereas gene families related to body hair and sensory receptors were contracted. Our analysis also identified whale-specific mutations in genes encoding antioxidants and enzymes controlling blood pressure and salt concentration. Overall the whale-genome sequences exhibited distinct features that are associated with the physiological and morphological changes needed for life in an aquatic environment, marked by resistance to physiological stresses caused by a lack of oxygen, increased amounts of reactive oxygen species and high salt levels.

The JAK/STAT3 signaling pathway plays an essential role in various types of cancers. Activation of this pathway leads to increased tumorigenic and metastatic ability, the transition of cancer stem cells (CSCs), and chemoresistance in cancer via enhancing the epithelial–mesenchymal transition (EMT). EMT acts as a critical regulator in the progression of cancer and is involved in regulating invasion, spread, and survival. Furthermore, accumulating evidence indicates the failure of conventional therapies due to the acquisition of CSC properties. In this review, we summarize the effects of JAK/STAT3 activation on EMT and the generation of CSCs. Moreover, we discuss cutting-edge data on the link between EMT and CSCs in the tumor microenvironment that involves a previously unknown function of miRNAs, and also discuss new regulators of the JAK/STAT3 signaling pathway.

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