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.

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

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.

After ACL injury, isokinetic extensor muscle strength and functional status of the contralateral limb were reduced, even at 24 months after ACL reconstruction. However, both measurements improved significantly as the follow-up time progressed. In contrast, flexion muscle strength was restored to normal levels. Therefore, care should be taken to restore muscle strength and functional status in not only the ACL-reconstructed knee but also the uninjured limb.

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BackgroundWith the rapid increasing use of third generation (3 G) mobile phones, social concerns have arisen concerning the possible health effects of radio frequency-electromagnetic fields (RF-EMFs) emitted by wideband code division multiple access (WCDMA) mobile phones in humans. The number of people, who complain of various symptoms such as headache, dizziness, and fatigue, has also increased. Recently, the importance of researches on teenagers has been on the rise. However, very few provocation studies have examined the health effects of WCDMA mobile phone radiation on teenagers.MethodsIn this double-blind study, two volunteer groups of 26 adults and 26 teenagers were simultaneously investigated by measuring physiological changes in heart rate, respiration rate, and heart rate variability for autonomic nervous system (ANS), eight subjective symptoms, and perception of RF-EMFs during sham and real exposure sessions to verify its effects on adults and teenagers. Experiments were conducted using a dummy phone containing a WCDMA module (average power, 250 mW at 1950 MHz; specific absorption rate, 1.57 W/kg) within a headset placed on the head for 32 min.ResultsShort-term WCDMA RF-EMFs generated no significant changes in ANS, subjective symptoms or the percentages of those who believed they were being exposed in either group.ConclusionsConsidering the analyzed physiological data, the subjective symptoms surveyed, and the percentages of those who believed they were being exposed, 32 min of RF radiation emitted by WCDMA mobile phones demonstrated no effects in either adult or teenager subjects.

High-mobility group box 1 protein (HMGB1), which mainly exists in the nucleus, has recently been shown to function as a sentinel molecule for viral nucleic acid sensing and an autophagy regulator in the cytoplasm. In this study, we studied the chaperone-like activity of HMGB1 and found that HMGB1 inhibited the chemically induced aggregation of insulin and lysozyme, as well as the heat-induced aggregation of citrate synthase. HMGB1 also restored the heat-induced suppression of cytoplasmic luciferase activity as a reporter protein in hamster lung fibroblast O23 cells with expression of HMGB1. Next, we demonstrated that HMGB1 inhibited the formation of aggregates and toxicity caused by expanded polyglutamine (polyQ), one of the main causes of Huntington disease. HMGB1 directly interacted with polyQ on immunofluorescence and coimmunoprecipitation assay, whereas the overexpression of HMGB1 or exogenous administration of recombinant HMGB1 protein remarkably reduced polyQ aggregates in SHSY5Y cells and hmgb1−/− mouse embryonic fibroblasts upon filter trap and immunofluorescence assay. Finally, overexpressed HMGB1 proteins in mouse embryonic primary striatal neurons also bound to polyQ and decreased the formation of polyQ aggregates. To this end, we have demonstrated that HMGB1 exhibits chaperone-like activity and a possible therapeutic candidate in polyQ disease.