Recently, sarcopenia has garnered renewed interest. Sarcopenia is a disease characterized by decreased skeletal muscle mass and strength/function, which can impair the quality of life and increase ...physical disability, adverse metabolic effects, and mortality. Imaging tools for evaluating and diagnosing sarcopenia have developed rapidly. Radiologists should be aware of sarcopenia and its clinical implications. We review current knowledge about sarcopenia, its pathophysiological impact, and advantages and disadvantages of methods for evaluation of sarcopenia focusing on body composition imaging modalities such as whole-body dual-energy X-ray absorptiometry, CT, and MRI. Controversial issues are discussed, including the lack of consensus and standardization of the disease definition, imaging modality, measurement methods, and diagnostic cutoff points.
Highlights • We observed upregulation of SRSF 5–7 proteins in SCLC tissue for the first time. • SRSF 5–7 protein levels in SCLC were higher than in ADC or SQC types of NSCLC. • SRSFs 5–7 detected ...SCLC in the lung more efficiently than CEA or proGRP. • SRSF5 showed great diagnostic potential for SCLC and extrapulmonary cancer in PE. • SRSF5 is a novel marker for SCLC and extrapulmonary pleural metastatic cancer.
Dietary procyanidin has been shown to be an important bioactive component that regulates various pharmacological activities to maintain metabolic homeostasis. In particular, grape seed ...proanthocyanidin extract (GSPE) is a commercially available medicine for the treatment of venous and lymphatic dysfunction. This study aimed to investigate whether GSPE protects against lipopolysaccharide (LPS)-induced bone loss in vivo and the related mechanism of action in vitro. The administration of GSPE restored the inflammatory bone loss phenotype stimulated by acute systemic injection of LPS in vivo. GSPE strongly suppressed receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and bone resorption activity of mature osteoclasts by decreasing the RANKL-induced nuclear factor-κB transcription activity. GSPE mediates this effect through decreased phosphorylation and degradation of NF-κB inhibitor (IκB) by IκB kinaseβ, subsequently inhibiting proto-oncogene cellular Fos and nuclear factor of activated T cells. Additionally, GSPE promotes osteoclast proliferation by increasing the phosphorylation of components of the Akt and mitogen-activated protein kinase signaling pathways and it also inhibits apoptosis by decreasing the activity of caspase-8, caspase-9, and caspase-3, as corroborated by a decrease in the Terminal deoxynucleotidyl transferase dUTP nick end labeling -positive cells. Our study suggests a direct effect of GSPE on the proliferation, differentiation, and apoptosis of osteoclasts and reveals the mechanism responsible for the therapeutic potential of GSPE in osteoclast-associated bone metabolism disease.
Adipose tissue is highly vascularized and requires the angiogenic properties for its mass growth. Visfatin has been recently characterized as a novel adipokine, which is preferentially produced by ...adipose tissue. In this study, we report that visfatin potently stimulates in vivo neovascularization in chick chorioallantoic membrane and mouse Matrigel plug. We also demonstrate that visfatin activates migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVECs). Moreover, visfatin evokes activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) in endothelial cells, which is closely linked to angiogenesis. Inhibition of ERK activation markedly decreases visfatin-induced tube formation of HUVECs and visfatin-stimulated endothelial cell sprouting from rat aortic rings. Taken together, these results demonstrate that visfatin promotes angiogenesis via activation of mitogen-activated protein kinase ERK-dependent pathway and suggest that visfatin may play important roles in various pathophysiological angiogenesis including adipose tissue angiogenesis.
Background
The assessment of liver surface nodularity (LSN) for staging hepatic fibrosis is restricted in clinical practice because it requires customized software and time‐consuming procedures. A ...simplified method to estimate LSN score may be useful in the clinic.
Purpose
To evaluate the regional analysis of LSN and processing time in a single axial liver MR image for staging liver fibrosis.
Study Type
Retrospective.
Population
A total of 210 subjects, a multicenter study.
Field Strength/Sequence
A 3 T/noncontrast gradient echo T1WI.
Assessment
Subjects were divided into five fibrosis groups (F0 = 29; F1 = 20; F2 = 32; F3 = 50; F4 = 79) based on the METAVIR fibrosis scoring system. The mean LSN (on three slices) and regional LSN (on one slice) measurements, and the processing times, are compared. The regional LSN scores in five regions‐of‐interests (ROI1‐5) were analyzed in a single axial MRI at the level of the hilum by two independent observers.
Statistical Tests
Regional variations in LSN scores were compared using ANOVA with Tukey test. Agreement between the mean and regional LSN measurements was evaluated using Pearson correlation coefficients (r) and Bland–Altman plots. The diagnostic performance of mean and regional LSN scores according to fibrosis stage was evaluated with the AUROC. A P value < 0.05 was considered statistically significant.
Results
Total processing time for a regional LSN measurement (3.6 min) was 75.5% less than that for mean LSN measurement (14.7 min). Mean LSN scores and all five regional LSN scores showed significant differences between fibrosis groups. Among regional LSN scores, ROI5 showed the highest AUROC (0.871 at cut‐off 1.12) for discriminating F0‐2 vs. F3‐4 and the best correlation with mean LSN score (r = 0.800, −0.07 limit of agreement).
Conclusion
Quantitative regional LSN measurement in a single axial MR image reduces processing time. Regional ROI5 LSN score might be useful for clinical decision‐making and for distinguishing the difference between early fibrosis (F0‐2) and advanced fibrosis (F3−4) in the liver.
Evidence Level
3
Technical Efficacy
Stage 2
Securinine (Sec) is a naturally derived compound separated from the roots of Securinega suffruticosa, which has long been used as a herbal medicine. Sec is widely known as a GABA receptor antagonist, ...it is also known as an innate immune cell agonist and has been reported to increase macrophage activity and promote monocyte maturation. On the basis of these studies, we investigated the effect of Sec on osteoclast differentiation and bone resorbing function. We have found that Sec inhibits RANKL‐induced osteoclast differentiation, fusion, actin ring formation, and bone resorbing function by the inhibition of gene expression associated with each stage. Moreover, Sec significantly suppressed osteoclastogenesis by decreasing the phosphorylation of p38, Akt, JNK, IκB, and PLCγ2, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c‐Fos and NFATc1. Finally, Sec effectively protected bone loss induced by the excessive inflammatory responses and activity of osteoclasts in vivo by a micro‐CT and histological analysis. In conclusion, our findings suggest that Sec may be a promising drug for bone metabolic diseases such as osteoporosis, which is associated with the excessive activity of osteoclasts.
Shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, induces necroptosis in various cancer types, but the mechanisms underlying the anticancer activity of shikonin in ...lung cancer are not fully understood. This study was designed to clarify whether shikonin causes necroptosis in non-small cell lung cancer (NSCLC) cells and to investigate the mechanism of action.
Multiplex and caspase 8 assays were used to analyze effect of shikonin on A549 cells. Cytometry with annexin V/PI staining and MTT assays were used to analyze the mode of cell death. Western blotting was used to determine the effect of shikonin-induced necroptosis and autophagy. Xenograft and orthotopic models with A549 cells were used to evaluate the anti-tumor effect of shikonin in vivo.
Most of the cell death induced by shikonin could be rescued by the specific necroptosis inhibitor necrostatin-1, but not by the general caspase inhibitor Z-VAD-FMK. Tumor growth was significantly lower in animals treated with shikonin than in the control group. Shikonin also increased RIP1 protein expression in tumor tissues. Autophagy inhibitors, including methyladenine (3-MA), ATG5 siRNA, and bafilomycin A, enhanced shikonin-induced necroptosis, whereas RIP1 siRNA had no effect on the apoptotic potential of shikonin.
Our data indicated that shikonin treatment induced necroptosis and autophagy in NSCLC cells. In addition, the inhibition of shikonin-induced autophagy enhanced necroptosis, suggesting that shikonin could be a novel therapeutic strategy against NSCLC.
Abstract
The edge-to-edge connected metal-semiconductor junction (MSJ) for two-dimensional (2D) transistors has the potential to reduce the contact length while improving the performance of the ...devices. However, typical 2D materials are thermally and chemically unstable, which impedes the reproducible achievement of high-quality edge contacts. Here we present a scalable synthetic strategy to fabricate low-resistance edge contacts to atomic transistors using a thermally stable 2D metal, PtTe
2
. The use of PtTe
2
as an epitaxial template enables the lateral growth of monolayer MoS
2
to achieve a PtTe
2
-MoS
2
MSJ with the thinnest possible, seamless atomic interface. The synthesized lateral heterojunction enables the reduced dimensions of Schottky barriers and enhanced carrier injection compared to counterparts composed of a vertical 3D metal contact. Furthermore, facile position-selected growth of PtTe
2
-MoS
2
MSJ arrays using conventional lithography can facilitate the design of device layouts with high processability, while providing low contact resistivity and ultrashort transfer length on wafer scales.
To assess the diagnostic performance of ultrasound (US) attenuation imaging (ATI) for diagnosis and grading of hepatic steatosis with comparison to magnetic resonance imaging-proton density fat ...fraction (MRI-PDFF) using mDIXON-Quant sequence.
Total 100 patients who underwent abdominal US ATI and MRI-PDFF within one month were included. Subjects were divided into three groups according to MRI-PDFF; Group 1 (no fatty liver), Q < 5.1%; Group 2 (mild fatty liver), 5.1% ≤ Q < 14.1%; and Group 3 (moderate fatty liver), Q ≥ 14.1%. US attenuation coefficients (AC) of enrolled patients were measured and correlated with MRI-PDFF. And their diagnostic performances were assessed. AC, MRI-PDFF, and liver function tests were compared among all groups.
Mean AC value of each group was as follows: Group 1 = 0.58 ± 0.11 dB/cm/MHz, Group 2 = 0.68 ± 0.08 dB/cm/MHz, and Group 3 = 0.77 ± 0.06 dB/cm/MHz. Mean AC value of each group of hepatic steatosis showed statistically significant difference (p < 0.001). There was a significant correlation between AC and MRI-PDFF in Pearson correlation (r = 0.751, p < 0.001). The area under the ROC curve (AUROC) of AC was 0.914 with sensitivity of 91.5%, and specificity of 80.0% for detection of mild fatty liver, and 0.935 for detection of moderate fatty liver with sensitivity of 93.3%, and specificity of 87.1%.
AC using ultrasound ATI showed high diagnostic performance and provided discriminative values for severity grading of fatty liver disease.
•Attenuation coefficient (AC) showed significant positive correlation with MRI-PDFF.•US AC showed high diagnostic performance for detection and grading of fatty liver.•US ATI is a reliable tool for the quantitative assessment of hepatic steatosis.