ObjectiveTo assess the safety and efficacy of 2 repeated intrathecal injections of autologous bone marrow–derived mesenchymal stem cells (BM‐MSCs) in amyotrophic lateral sclerosis (ALS).MethodsIn a phase 2 randomized controlled trial (NCT01363401), 64 participants with ALS were randomly assigned treatments (1:1) of riluzole alone (control group, n = 31) or combined with 2 BM‐MSC injections (MSC group, n = 33). Safety was assessed based on the occurrence of adverse events. The primary efficacy outcome was changes in Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS‐R) score from baseline to 4 and 6 months postinjection. Post hoc analysis includes investigation of cerebrospinal fluid biomarkers and long‐term survival analysis.ResultsSafety rating showed no groupwise difference with absence of serious treatment‐related adverse events. Mean changes in ALSFRS‐R scores from baseline to 4 and 6 months postinjection were reduced in the MSC group compared with the control group (4 months: 2.98, 95% confidence interval [CI] = 1.48–4.47, p < 0.001; 6 months: 3.38, 95% CI = 1.23–5.54, p = 0.003). The MSC group showed decreased proinflammatory and increased anti‐inflammatory cytokines. In good responders, transforming growth factor β1 significantly showed inverse correlation with monocyte chemoattractant protein‐1. There was no significant difference in long‐term survival between groups.InterpretationRepeated intrathecal injections of BM‐MSCs demonstrated a possible clinical benefit lasting at least 6 months, with safety, in ALS patients. A plausible action mechanism is that BM‐MSCs mediate switching from pro‐ to anti‐inflammatory conditions. A future randomized, double‐blind, large‐scale phase 3 clinical trial with additional BM‐MSC treatments is required to evaluate long‐term efficacy and safety. Ann Neurol 2018;84:361–373

These results demonstrate that ROS mediate high glucose-induced up-regulation of PAI-1 expression in cultured mesangial cells and in diabetic glomeruli. Since both high glucose and TGF-beta1 induce cellular ROS and ROS mediate both high glucose- and TGF-beta1-induced PAI-1, ROS appear to amplify TGF-beta1 signaling in high glucose-induced PAI-1 up-regulation. Antioxidants can prevent accumulation of ECM protein in diabetic glomeruli partly by abrogating up-regulation of PAI-1 and suppression of plasmin activity.

Many factors are associated with the development of low back pain. Among them, exercise, obesity, smoking, age, educational level and stress are the most common. This study examined the association of these factors with low back pain. An additional aim was to determine a procedure for preventing low back pain. This study analyzed the responses to a questionnaire sent to 772 individuals who had undergone a medical examination at this hospital in 2003 and excluded the individuals who had shown symptoms or their test results indicated a particular disease. Assuming that there were no variables, individuals who exercised regularly 3-4 times per week would have a lower chance of having low back pain than those who did not exercise regularly. The analysis revealed that individuals with a college degree or higher education have a lower chance of experiencing low back pain than those with only a high school education or even college drop-outs. When the other variables were constant, age, extent of obesity (body mass index), smoking and level of stress were not found to affect the development of low back pain. The level of education was associated with the development of low back pain. However, regular exercise 3-4 times per week or more would be most effective in reducing the incidence and duration of low back pain.

In two-dimensional interfacial assemblies, there is an interplay between molecular ordering and interface geometry, which determines the final morphology and order of entire systems. Here we present the interfacial phenomenon of spontaneous facet formation in a water droplet driven by designed peptide assembly. The identified peptides can flatten the rounded top of a hemispherical droplet into a plane by forming a macroscopic two-dimensional crystal structure. Such ordering is driven by the folding geometry of the peptide, interactions of tyrosine and crosslinked stabilization by cysteine. We discover the key sequence motifs and folding structures and study their sequence-specific assembly. The well-ordered, densely packed, redox-active tyrosine units in the YYACAYY (H-Tyr-Tyr-Ala-Cys-Ala-Tyr-Tyr-OH) film can trigger or enhance chemical/electrochemical reactions, and can potentially serve as a platform to fabricate a molecularly tunable, self-repairable, flat peptide or hybrid film.