Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic ...lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo
mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.
Background
Little information is currently available on the development of tubulointerstitial lesions in children with Henoch–Schönlein nephritis (HSN). To identify the impact of the development of ...tubulointerstitial changes in HSN, we retrospectively analyzed renal biopsies obtained from children with HSN.
Methods
Twenty-eight children with HSN from whom serial renal biopsies had been obtained before and after immunosuppressive therapy were enrolled in the study. The patients were divided into two groups according to the observed change in tubulointerstitial lesion development: group I (
n
= 15), with stable or improved tubulointerstitial lesions, and group II (
n
= 13), with worsened tubulointerstitial lesions. Group II patients had longer duration of proteinuria than group I patients (3.7 ± 3.7 years vs. 1.7 ± 1.7 years,
p
= 0.052).
Results
The change in serum albumin level was negatively correlated with the change in tubulointerstitial scores before and after treatment (γ = −0.444,
p
= 0.018). Group II patients showed a significant decrease in immunoglobulin G (IgG) and IgA deposits after treatment (
p
= 0.039 and 0.003, respectively), while group II patients did not (
p
= 0.458 and 0.506, respectively).
Conclusions
Although the International Study of Kidney Disease in Children classification of HSN does not include tubulointerstitial lesions, they can progress during treatment and could have significant clinical implications in association with the duration of proteinuria.
Background and aims:
Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study ...aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side.
Methods:
Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden’s index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side.
Results:
Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. Scatterplot cutoffs of RIR <0.5 or >7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity.
Conclusion:
In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.
•For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality.•A higher risk of all-cause mortality was observed in ...patients with lower LDL-cholesterol levels for the large artery atherosclerosis subtype.•Patients with higher LDL-cholesterol levels had a higher risk of all-cause mortality for the cardioembolic stroke subtype.•There were U-shaped associations of LDL-cholesterol levels on early vascular outcomes in acute ischemic stroke patients.
Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients.
This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months.
A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (Pinteraction=0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio aHR 1.29, 95% confidence interval CI 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI 1.28-2.29), were observed among stroke subtypes.
We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes.
To establish and characterize radiation-induced esophagitis (RIE) in vivo and in vitro.
Fractionated thoracic irradiation at 0, 8, 12, or 15 Gy was given daily for 5 days to Balb/c or C57Bl/6 mice. ...Changes in body weight gain and daily food intake were assessed. At the end of the study, we removed the esophagus and examined histology by hematoxylin and eosin staining, immune cell infiltration and apoptosis by fluorescence-activated cell sorting, and gene expression changes by quantitative real-time polymerase chain reaction. Het-1A human esophageal epithelial cells were irradiated at 6 Gy, treated with recombinant human growth factors, and examined for gene expression changes, apoptosis, proliferation, and signal transduction pathways.
We observed that irradiation at 12 Gy or 15 Gy per fraction produced significant reduction in body weight and decreased food intake in Balb/c mice but not as much in C57Bl/6 mice. Further analyses of Balb/c mice irradiated at 12 Gy/fraction revealed attenuated epithelium, inflamed mucosa, and increased numbers of infiltrating CD4+ helper T cells and apoptotic cells. Moreover, we found that expression of tissue inhibitor for metalloproteinase-1, plasminogen activator inhibitor-1, granulocyte macrophage-colony stimulating factor, vascular endothelial growth factor, and stromal-derived factor-1 were increased, whereas epidermal growth factor (EGF) was decreased. Irradiated Het-1A cells similarly showed a significant decrease in expression of EGF and connective tissue growth factor (CTGF). Treatment of EGF but not CTGF partially protected Het-1A cells from radiation-induced apoptosis and revealed phosphorylation of EGFR, AKT, and ERK signaling pathways.
We established a mouse model of RIE in Balb/c mice with 12 Gy × 5 fractions, which showed reduced body weight gain, food intake, and histopathologic features similar to those of human esophagitis. Decreased EGF expression in the irradiated esophagus suggests that EGF may be a potential therapeutic intervention strategy to treat RIE.
Two-dimensional (2D) siloxene is attracting considerable research interest recently principally owing to its inherent compatibility with silicon-based semiconductor technology. -The synthesis of ...siloxene has been mostly limited to multilayered structures using traditional topochemical reaction procedures. Herein, we report high-yield synthesis of single to few-layer siloxene nanosheets by developing a two-step interlayer expansion and subsequent liquid phase exfoliation procedure. Our protocol enables high-yield production of few-layer siloxene nanosheets with a lateral dimension of up to 4 μm and thickness ranging from 0.8 to 4.8 nm, corresponding to single to a few layers, well stabilized in water. The atomically flat nature of exfoliated siloxene can be exploited for the construction of 2D/2D heterostructure membranes via typical solution processing. We demonstrate highly ordered graphene/siloxene heterostructure films with synergistic mechanical and electrical properties, which deliver noticeably high device capacitance when assembled into a coin cell symmetric supercapacitor device structures. Additionally, we demonstrate that the mechanically flexible exfoliated siloxene-graphene heterostructure enables its direct use in flexible and wearable supercapacitor applications.
Clinicians sometimes treat patients with relatively long-duration geotropic direction-changing positional nystagmus (DCPN), without latency. Recently, the concept of a "light cupula" in the lateral ...canal that reveals persistent geotropic DCPN has been introduced. In the present study, we investigated the immediate and short-term therapeutic findings in long-duration DCPN.
The authors prospectively compared the therapeutic efficacy of a canalith-repositioning procedure (CRP) in short- and long-duration geotropic DCPN.
In patients with long-duration DCPN, the authors found no immediate therapeutic effect, and the number of patients showing short-term effects (on the next day) was very low compared with the comparable figure among those with short-duration DCPN. In addition, no cases exhibited canal conversion after the CRP.
Our results suggest that CRP is not useful in patients with long-duration geotropic DCPN, and the pathogenesis of long-duration geotropic DCPN may not originate from free-floating debris but from deflection of the cupula.
•Pro B2 elevated the expression of IRAK-M, a negative regulator of TLR signaling.•LPS-induced expression of cell surface molecules was inhibited by Pro B2.•LPS-induced production of pro-inflammatory ...cytokines was inhibited by Pro B2.•Pro B2 inhibited LPS-induced activation of MAPKs and NF-κB through IRAK-M.•Pro B2 inactivated naïve T cells by inhibiting LPS-induced cytokines via IRAK-M.
Polyphenolic compounds have been found to possess a wide range of physiological activities that may contribute to their beneficial effects against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain to be elucidated. In this study, we investigated the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by procyanidin dimer B2 (Pro B2) in macrophages. Pro B2 markedly elevated the expression of the interleukin (IL)-1 receptor-associated kinase (IRAK)-M protein, a negative regulator of TLR signaling. Lipopolysaccharide (LPS)-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by Pro B2, and this action was prevented by IRAK-M silencing. In addition, Pro B2-treated macrophages inhibited LPS-induced activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase and the translocation of nuclear factor κB and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated naïve T cells by inhibiting LPS-induced interferon-γ and IL-2 secretion through IRAK-M. These novel findings provide new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and the immune-pharmacological role of Pro B2 in the immune response against the development and progression of many chronic diseases.
The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors ...affecting the extrusion rate, recurrence rate, and complications of VT insertion.
A prospective study was conducted between June 2014 and December 2016 (the EVENT study analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media), with follow-up data collected until the end of 2017. Patients aged <15 years diagnosed with otitis media with effusion who received VT insertion were recruited at 15 tertiary hospitals. The primary outcomes were time to extrusion of VT, time to effusion recurrence, and complications.
Data from 401 patients were analyzed. After excluding the.
of long-lasting tubes (Paparella type II and T-tubes), silicone tubes (Paparella type I) exhibited a significantly longer extended time to extrusion (mean, 400 days) than titanium tubes (collar-button-type 1.0 mm: mean, 312 days; P<0.001). VT material (hazard ratio HR, 2.117, 95% confidence interval CI, 1.254-3.572; P=0.005), age (HR, 3.949; 95% CI, 1.239-12.590; P=0.02), and effusion composition (P=0.005) were significantly associated with the time to recurrence of middle ear effusion. Ears with purulent (mean, 567 days) and glue-like (mean, 588 days) effusions exhibited a shorter time to recurrence than ears with serous (mean, 846 days) or mucoid (mean, 925 days) effusions. The revision VT rates during follow-up were 3.5%, 15.5%, 10.4%, and 38.9% in ears with serous, mucoid, glue-like, and purulent effusions, respectively (P<0.001). The revision surgery rates were higher among patients aged <7 years than among those aged ≥7 years.
Silicone tubes (Paparella type I) were less prone to early extrusion than titanium 1.0 mm tubes. VT type, patient age, and effusion composition affected the time to recurrence of effusion.
PDF
