Evaluation of the accuracy of mobile cone-beam computed tomography after spinal instrumentation surgery.

Purpose: Pedicle screw fixation provides 3-column stabilization, multidimensional control, and a higher rate of interbody fusion. Although computed tomography (CT) is recommended for the postoperative assessment of pedicle screw fixation, its use is limited due to the radiation exposure dose. The purpose of this preliminary retrospective study was to assess the clinical usefulness of low-dose mobile cone-beam CT (CBCT) for the postoperative evaluation of pedicle screw fixation. Methods: The author retrospectively reviewed postoperative mobile CBCT images of 15 patients who underwent posterior pedicle screw fixation for spinal disease from November 2019 to April 2020. Pedicle screw placement was assessed for breaches of the bony structures. The breaches were graded based on the Heary classification. Results: The patients included 11 men and four women, and their mean age was 66±12 years. Of the 122 pedicle screws, 34 (27.9%) were inserted in the thoracic segment (from T7 to T12), 82 (67.2%) in the lumbar segment (from L1 to L5), and six (4.9%) in the first sacral segment. Although there were metal-related artifacts, the image of the screw position (according to Heary classification) after surgery could be assessed using mobile CBCT at all levels (T7-S1). Conclusions: Mobile CBCT was accurate in determining the location and integrity of the pedicle screw and identifying the surrounding bony structures. In the postoperative setting, mobile CBCT can be used as a primary modality for assessing the accuracy of pedicle screw fixation and detecting postoperative complications.

Assessment of Liver Fibrosis Stage Using Integrative Analysis of Hepatic Heterogeneity and Nodularity in Routine MRI with FIB-4 Index as Reference Standard.

Image-based quantitative methods for liver heterogeneity (LHet) and nodularity (LNod) provide helpful information for evaluating liver fibrosis; however, their combinations are not fully understood in liver diseases. We developed an integrated software for assessing LHet and LNod and compared LHet and LNod according to fibrosis stages in chronic liver disease (CLD). Overall, 111 CLD patients and 16 subjects with suspected liver disease who underwent liver biopsy were enrolled. The procedures for quantifying LHet and LNod were bias correction, contour detection, liver segmentation, and LHet and LNod measurements. LHet and LNod scores among fibrosis stages (F0-F3) were compared using ANOVA with Tukey's test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (AUROC) curve. The mean LHet scores of F0, F1, F2, and F3 were 3.49 ± 0.34, 5.52 ± 0.88, 6.80 ± 0.97, and 7.56 ± 1.79, respectively (p < 0.001). The mean LNod scores of F0, F1, F2, and F3 were 0.84 ± 0.06, 0.91 ± 0.04, 1.09 ± 0.08, and 1.15 ± 0.14, respectively (p < 0.001). The combined LHet × LNod scores of F0, F1, F2, and F3 were 2.96 ± 0.46, 5.01 ± 0.91, 7.30 ± 0.89, and 8.48 ± 1.34, respectively (p < 0.001). The AUROCs of LHet, LNod, and LHet × LNod for differentiating F1 vs. F2 and F2 vs. F3 were 0.845, 0.958, and 0.954; and 0.619, 0.689, and 0.761, respectively. The combination of LHet and LNod scores derived from routine MR images allows better differential diagnosis of fibrosis subgroups in CLD.

Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation.

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 kinaseß, 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.

Staging of Liver Fibrosis by Means of Semiautomatic Measurement of Liver Surface Nodularity in MRI.

OBJECTIVE. The purposes of this study were to evaluate the accuracy of a semiautomatic method of measuring liver surface nodularity (LSN) on contrast-enhanced MR images and to compare the LSN score with pathologic fibrosis stage. MATERIALS AND METHODS. This retrospective study included patients who had undergone gadoxetate disodium-enhanced liver MRI 6 months before or after histopathologic investigation including percutaneous parenchymal biopsy and surgical biopsy for staging of chronic liver disease between January 2010 and December 2018. Semiautomated LSN quantification software was developed to measure LSN at MRI. Aspartate aminotransferase to platelet ratio index and fibrosis-4 index were derived from serum laboratory test results. The reference standard for staging of liver fibrosis was Metavir score. The accuracy of LSN score for staging of liver fibrosis was evaluated with AUC, and the optimal cutoff value was calculated by Youden index. Spearman correlation coefficient was used for correlation analysis. RESULTS. The study included 132 patients (93 men, 39 women). LSN score was evaluated without technical failure. There was high correlation between LSN score and Metavir score (Spearman ρ = 0.713, p < 0.001). The AUCs of LSN score for distinguishing Metavir score were 0.93 for F0-F1 versus F2-F4 (95% CI, 0.88-0.97; p < 0.001), 0.98 for F0-F2 vs F3-F4 (95% CI, 0.95-1.00; p < 0.001), and 0.83 for F0-F3 versus F4 (95% CI, 0.76-0.90; p < 0.001). The optimal cutoff value for differentiating F0-F2 from F3-F4 was 0.850 with 100% sensitivity and 85.4% specificity. CONCLUSION. LSN score calculated semiautomatically from MR images of the liver has high accuracy and correlates directly with the pathologic fibrosis stage.

Betulinic Acid Inhibits RANKL-Induced Osteoclastogenesis via Attenuating Akt, NF-κB, and PLCγ2-Ca2+ Signaling and Prevents Inflammatory Bone Loss.

The increase of bone-resorbing osteoclast activity in bone remodeling is the major characteristic of various bone diseases. Thus, inhibiting osteoclastogenesis and bone-resorbing function may be an effective therapeutic target for bone diseases. Betulinic acid (BA), a natural plant-derived pentacyclic triterpenoid compound, is known to possess numerous pharmacological and biochemical properties including anti-inflammatory, anticancer, and antiadipogenic activity. However, the effect of BA on osteoclast differentiation and function in bone metabolism has not been demonstrated so far. In this study, we investigated whether BA could suppress RANKL-induced osteoclastogenesis and bone resorption. Interestingly, BA significantly suppressed osteoclastogenesis by decreasing the phosphorylation of Akt and IκB, as well as PLCγ2-Ca2+ signaling, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c-Fos and NFATc1. The inhibition of these pathways by BA was once more confirmed by retrovirus infection of constitutively active (CA)-Akt and CA-Ikkß retrovirus and measurement of Ca2+ influx. BA also significantly inhibited the expression of osteoclastogenesis-specific marker genes. Moreover, we found that BA administration restored the bone loss induced through acute lipopolysaccharide injection in mice by a micro-CT and histological analysis. Our findings suggest that BA is a potential therapeutic candidate for bone diseases involving osteoclasts.

Accuracy of proton magnetic resonance for diagnosing non-alcoholic steatohepatitis: a meta-analysis.

Liver biopsy is the reference standard test to differentiate between non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) in non-alcoholic fatty liver disease (NAFLD), but noninvasive diagnostics are warranted. The diagnostic accuracy in NASH using MR imaging modality have not yet been clearly identified. This study was assessed the accuracy of magnetic resonance imaging (MRI) method for diagnosing NASH. Data were extracted from research articles obtained after a literature search from multiple electronic databases. Random-effects meta-analyses were performed to obtain overall effect size of the area under the receiver operating characteristic(ROC) curve, sensitivity, specificity, likelihood ratios(LR), diagnostic odds ratio(DOR) of MRI method in detecting histopathologically-proven SS(or non-NASH) and NASH. Seven studies were analyzed 485 patients, which included 207 SS and 278 NASH. The pooled sensitivity was 87.4% (95% CI, 76.4-95.3) and specificity was 74.3% (95% CI, 62.4-84.6). Pooled positive LR was 2.59 (95% CI, 1.96-3.42) and negative LR was 0.17 (95% CI, 0.07-0.38). DOR was 21.57 (95% CI, 7.27-63.99). The area under the curve of summary ROC was 0.89. Our meta-analysis shows that the MRI-based diagnostic methods are valuable additions in detecting NASH.

Umbelliferone Prevents Lipopolysaccharide-Induced Bone Loss and Suppresses RANKL-Induced Osteoclastogenesis by Attenuating Akt-c-Fos-NFATc1 Signaling.

Excessive bone resorption plays a central role in the development of inflammatory bone diseases, including osteoporosis and rheumatoid arthritis. Thus, identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for the prevention and treatment of inflammatory bone loss. Umbelliferone (Umb), a derivative of coumarin, is a natural bioactive compound with anti-inflammatory and antioxidant properties. However, the effect of Umb on metabolic bone diseases is unknown. In this study, we found that Umb exhibited a strong inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory bone loss in vivo. Histological analysis confirmed that Umb prevented trabecular bone matrix degradation and osteoclast formation in bone tissue. In addition, Umb suppressed RANKL-induced osteoclast differentiation and abrogated bone resorption. We found that the anti-osteoclastic and anti-resorptive activities of Umb are mediated via suppression of the RANKL-induced Akt-c-Fos-NFATc1 signaling pathway and the attenuation of osteoclast-specific genes, such as TRAP, OSCAR, ATP6v0d2, and CtsK. In particular, Umb downregulated the stability of c-Fos and NFATc1 proteins, but did not suppress the expression of their mRNAs. These results indicate that Umb may be a potential therapeutic agent for inflammatory bone diseases associated with abnormal osteoclast formation and function.

Role of ANTXR1 in the regulation of RANKL-induced osteoclast differentiation and function.

Anthrax toxin receptor 1 (ANTXR1) is a transmembrane protein with an extracellular domain which is deeply associated with the process of bone formation and plays an important role in angiogenesis. However, there have been no reports investigating the effects of ANTXR1 on bone metabolism mediated by the two types of bone cells, osteoclasts, and osteoblasts. The aim of this study is to reveal the role of ANTXR1 in the differentiation and function of osteoclasts and osteoblasts. We found that ANTXR1 positively regulated the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation and bone resorption with no effects on osteoblast differentiation by performing gain- and loss-of-function studies. During ANTXR1-mediated regulation of osteoclastogenesis, phosphorylation of early signal transducers such as c-Jun N-terminal kinase (JNK), Akt, inhibitor of kappa B (IκB), and phospholipase C gamma 2 (PLCγ2) was affected, which in turn altered the mRNA and protein levels of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In addition, genetic manipulation of ANTXR1 in bone marrow macrophages (BMMs) modulated the capillary-like tube formation in HUVECs via secretion of two angiogenic factors, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor-A (VEGF-A). These results elucidated the importance of ANTXR1 in osteoclast differentiation and functional activity, as well as, osteoclast-mediated angiogenesis of endothelial cells. Taken together, we propose that ANTXR1 might be a promising candidate for gene therapy for bone metabolic diseases and further, might potentially serve as an important biomarker in the field of bone metastasis associated with vascularization.

Noninvasive Differential Diagnosis of Liver Iron Contents in Nonalcoholic Steatohepatitis and Simple Steatosis Using Multiecho Dixon Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: The roles of iron stores in nonalcoholic fatty liver disease have not yet been clearly identified, and it is lack of uniform criteria and a standardized study design for assessing the liver iron content (LIC) in nonalcoholic steatohepatitis (NASH). This study was to compare LICs in biopsy-proven simple steatosis (SS) and NASH based on T2⁎-relaxometry. MATERIAL AND METHODS: A total of 32 subjects divided to three groups, consisting of 10 healthy controls, 12 SS and 10 NASH. All MRI examinations were performed on a 3 T MRI with a 32-channel body coil. To measure T2⁎-value, we used a gradient echo sequence with six multiechoes within a single breath-hold. Hepatic iron contents among three groups were compared using Kruskal-Wallis H test and Mann-Whitney's posthoc tests. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics curve. To identify the reliability of iron measurements in the different region of interests, coefficient of variance (CV) was calculated overall CV values for the variability of measurements. Interobserver agreement and reliability were estimated by calculating the intraclass correlation coefficient. RESULTS: The variations of all LIC measurements are not exceeded 20%, as a mean CV value 18.3%. intraclass correlation coefficients were higher than 0.9. Mean T2⁎-values at localized region of interests were healthy controls 45.42 ± 7.19 ms, SS 20.96 ± 4.28 ms, and NASH 15.49 ± 2.87 ms. The mean T2⁎-value in NASH is significantly shorter than that in SS (p = 0.008). The area under the receiver operating characteristics curve to distinguish NASH from SS was 0.908 (95% confidence interval 0.775-1.000, p = 0.001) at a cut-off of iron contents greater than 17.95 ms, and its diagnostic accuracy had 0.833 sensitivity and 0.800 specificity. CONCLUSION: This study demonstrates that the T2⁎ calculation can help to differentially diagnose NASH.

Automatic Lung Segmentation With Juxta-Pleural Nodule Identification Using Active Contour Model and Bayesian Approach.

OBJECTIVE: chest computed tomography (CT) images and their quantitative analyses have become increasingly important for a variety of purposes, including lung parenchyma density analysis, airway analysis, diaphragm mechanics analysis, and nodule detection for cancer screening. Lung segmentation is an important prerequisite step for automatic image analysis. We propose a novel lung segmentation method to minimize the juxta-pleural nodule issue, a notorious challenge in the applications. METHOD: we initially used the Chan-Vese (CV) model for active lung contours and adopted a Bayesian approach based on the CV model results, which predicts the lung image based on the segmented lung contour in the previous frame image or neighboring upper frame image. Among the resultant juxta-pleural nodule candidates, false positives were eliminated through concave points detection and circle/ellipse Hough transform. Finally, the lung contour was modified by adding the final nodule candidates to the area of the CV model results. RESULTS: to evaluate the proposed method, we collected chest CT digital imaging and communications in medicine images of 84 anonymous subjects, including 42 subjects with juxta-pleural nodules. There were 16 873 images in total. Among the images, 314 included juxta-pleural nodules. Our method exhibited a disc similarity coefficient of 0.9809, modified hausdorff distance of 0.4806, sensitivity of 0.9785, specificity of 0.9981, accuracy of 0.9964, and juxta-pleural nodule detection rate of 96%. It outperformed existing methods, such as the CV model used alone, the normalized CV model, and the snake algorithm. Clinical impact: the high accuracy with the juxta-pleural nodule detection in the lung segmentation can be beneficial for any computer aided diagnosis system that uses lung segmentation as an initial step.

Claudin 11 regulates bone homeostasis via bidirectional EphB4-EphrinB2 signaling.

Claudins (Cldns) are well-established components of tight junctions (TJs) that play a pivotal role in the modulation of paracellular permeability. Several studies have explored the physiologic aspects of Cldn family members in bone metabolism. However, the effect of Cldn11, a major component of central nervous system myelin, on bone homeostasis has not been reported. In this study, we demonstrate that Cldn11 is a potential target for bone disease therapeutics as a dual modulator of osteogenesis enhancement and osteoclastogenesis inhibition. We found that Cldn11 played a negative role in the receptor activator of nuclear factor kappa B ligand-induced osteoclast (OC) differentiation and function by downregulating the phosphorylated form of extracellular signal-regulated kinase (ERK), Bruton's tyrosine kinase, and phospholipase C gamma 2, in turn impeding c-Fos and nuclear factor in activated T cell c1 expression. The enhancement of osteoblast (OB) differentiation by positive feedback of Cldn11 was achieved through the phosphorylation of Smad1/5/8, ERK, and c-Jun amino-terminal kinase. Importantly, this Cldn11-dependent dual event in bone metabolism arose from targeting EphrinB2 ligand reverse signaling in OC and EphB4 receptor forward signaling in OB. In agreement with these in vitro effects, subcutaneous injection of Cldn11 recombinant protein exerted anti-resorbing effects in a lipopolysaccharide-induced calvarial bone loss mouse model and increased osteogenic activity in a calvarial bone formation model. These findings suggest that Cldn11 is a novel regulator in bone homeostasis.

Coefficient of variation on Gd-EOB MR imaging: Correlation with the presence of early-stage hepatocellular carcinoma in patients with chronic hepatitis B.

PURPOSE: To study whether the measurement of hepatic fibrosis on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance (MR) imaging using the coefficient of variation (CV) might be correlated with the presence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). MATERIALS AND METHODS: This study included 104 patients with and without CHB, who were divided into 4 groups: control group, CHB without liver cirrhosis (LC; Group I), CHB with LC (Group II), and CHB with LC and HCC (Group III). MR images were analyzed to measure the inhomogeneity of signal intensities calculated using the CV map of the liver parenchyma. Intergroup comparisons of CV values were performed using ANOVA. The diagnostic performance of the CV map and alpha-fetoprotein (AFP) for diagnosing HCC was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: On the hepatobiliary phase of Gd-EOB-DTPA-enhanced T1-weighted imaging, the mean CV values of the control group and Groups I, II, and III were 3.9 ±â€¯0.99, 3.97 ±â€¯1.09, 5.58 ±â€¯2.05, and 6.80 ±â€¯2.34, respectively (P = 0.000). On ROC analysis of the CV value for predicting HCC, the value of the area under the curve (AUC) on Gd-EOB-DTPA MR imaging was 0.788 (95% CI: 0.697-0.862). The sensitivity and specificity were 84.2% and 63.6%, respectively, at a CV cutoff value >4.75. The value of AUC determined using AFP was 0.766. CONCLUSION: The CV value for hepatic fibrosis on Gd-EOB-DTPA MR imaging may be correlated with the presence of HCC in patients with CHB, and shows comparable diagnostic performance to AFP analysis.

Computed tomography morphologic features of pulmonary adenocarcinoma with brain/bone metastasis.

BACKGROUND/AIMS: Brain and bone metastases are common in patients with lung cancer. The development of metastasis is associated with poor survival in lung cancer patients. Although tumor morphologic features on radiographs are routinely assessed for differentiation between benign and malignant lung nodules, they are not used to predict metastasis. We assessed morphologic features of pulmonary adenocarcinomas with brain/bone metastasis on computed tomography (CT) to identify related factors for metastasis. METHODS: We performed a retrospective analysis of initial chest CT findings (size, type of contour, percentage of necrosis, enhancement, presence or absence of calcification, and air cavity) from 2009 to 2010 of patients with brain or bone metastasis and compared the findings with those of patients without metastases. RESULTS: In total, 128 patients were included (78 men, 52 women; mean age 69 years; range, 36 to 87). Nineteen patients had brain metastases and 32 had bone metastases. Morphologic features associated with brain metastasis included size ≥ 50 mm (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.24 to 9.17; p = 0.013), necrosis ≥ 30% (OR, 4.51; 95% CI, 1.62 to 12.55; p =0.002), and presence of calcification (OR, 3.97; 95% CI, 1.16 to 13.55; p = 0.035). Morphologic features associated with bone metastasis included necrosis ≥ 30% (OR, 4.639; 95% CI, 1.98 to 10.82; p < 0.001) and T 3 to 4 stage (OR, 2.53; 95% CI, 1.07 to 6.00; p = 0.031). CONCLUSIONS: We found that necrosis ≥ 30% was associated with pulmonary adenocarcinoma with brain and bone metastasis at initial chest CT morphologic feature. To validate these results, further research should be conducted.

Diagnostic Significance of Measuring Vascular Endothelial Growth Factor for the Differentiation between Malignant and Tuberculous Pleural Effusion.

Malignancy and tuberculosis are common causes of lymphocytic exudative pleural effusion. However, it is occasionally difficult to differentiate malignant pleural effusion from tuberculous pleural effusion. Vascular endothelial growth factor (VEGF) is a critical cytokine in the pathogenesis of malignant pleural effusion. Endocan is a dermatan sulfate proteoglycan that is secreted by endothelial cells. Importantly, endocan mediates the vascular growth-promoting action of VEGF. The aim of this study was to evaluate the diagnostic significance of VEGF and endocan in pleural effusion. We thus measured the levels of VEGF and endocan in the pleural effusion and serum samples of patients with lung cancer (n = 59) and those with tuberculosis (n = 32) by enzyme-linked immunosorbent assay. Lung cancer included 40 cases of adenocarcinoma, 13 of squamous cell carcinoma, and 6 of small cell carcinoma. Pleural effusion VEGF levels were significantly higher in the malignant group than in the tuberculosis group (2,091.47 ± 1,624.80 pg/mL vs. 1,291.05 ± 1,100.53 pg/mL, P < 0.05), whereas pleural effusion endocan levels were similar between the two groups (1.22 ± 0.74 ng/mL vs. 0.87 ± 0.53 ng/mL). The areas under the curve of VEGF and endocan were 0.73 and 0.52, respectively. Notably, the VEGF levels were similar in malignant pleural effusion, irrespective of the histological type of lung cancer. Moreover, no significant difference was found in the serum VEGF and endocan levels between patients with lung cancer and those with tuberculosis. In conclusion, high VEGF levels in pleural effusion are suggestive of malignant pleural effusion.

Shikonin-induced necroptosis is enhanced by the inhibition of autophagy in non-small cell lung cancer cells.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluation of connectivity map-discovered celastrol as a radiosensitizing agent in a murine lung carcinoma model: Feasibility study of diffusion-weighted magnetic resonance imaging.

This study was designed to identify potential radiosensitizing (RS) agents for combined radio- and chemotherapy in a murine model of human lung carcinoma, and to evaluate the in vivo effect of the RS agents using diffusion-weighted magnetic resonance imaging (DW-MRI). Radioresistance-associated genes in A549 and H460 cells were isolated on the basis of their gene expression profiles. Celastrol was selected as a candidate RS by using connectivity mapping, and its efficacy in lung cancer radiotherapy was tested. Mice inoculated with A549 carcinoma cells were treated with single ionizing radiation (SIR), single celastrol (SC), or celastrol-combined ionizing radiation (CCIR). Changes in radiosensitization over time were assessed using DW-MRI before and at 3, 6, and 12 days after therapy initiation. The tumors were stained with hematoxylin and eosin at 6 and 12 days after therapy. The percentage change in the apparent diffusion coefficient (ADC) value in the CCIR group was significantly higher than that in the SC and SIR group on the 12th day (Mann-Whitney U-test, p = 0.05; Kruskal-Wallis test, p < 0.05). A significant correlation (Spearman's rho correlation coefficient of 0.713, p = 0.001) was observed between the mean percentage tumor necrotic area and the mean ADC values after therapy initiation. These results suggest that the novel radiosensitizing agent celastrol has therapeutic effects when combined with ionizing radiation (IR), thereby maximizing the therapeutic effect of radiation in non-small cell lung carcinoma. In addition, DW-MRI is a useful noninvasive tool to monitor the effects of RS agents by assessing cellularity changes and sequential therapeutic responses.

Contrast-enhanced ultrasound and computed tomography findings of granulomatosis with polyangiitis presenting with multiple intrarenal microaneurysms: A case report.

Granulomatosis with polyangiitis (GPA) is a systemic disorder that affects small- and medium- sized vessels in many organs. Although the kidneys are the second most commonly involved organ in patients with GPA, its manifestation as multiple intrarenal aneurysms is rare. We report an unusual manifestation of GPA with multiple intrarenal microaneurysms, as demonstrated by contrast-enhanced ultrasound and computed tomography.

Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss.

In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP) staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR). Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca2+ influx intensity (staining with Fluo-3/AM). Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time.

PURPOSE: To evaluate the hepatic metabolic alterations in nonalcoholic fatty liver disease (NAFLD) by using 1 H-MRS (proton magnetic resonance spectroscopy) with long echo time and to test the reproducibility of human study in an animal model. Liver biopsy is the gold standard for diagnosing NAFLD but with practical constraints. 1 H-MRS allows in vivo assessment of hepatocellular metabolism and has shown potential for biochemical differentiation in diffuse liver disease. MATERIALS AND METHODS: In all, 32 subjects (11 patients with nonalcoholic steatohepatitis [NASH], 15 with simple steatosis [SS], and six healthy controls) were studied. For test reproducibility, 36 C57BL/6 mice, including 10 mice with streptozotocin-induced NASH, 15 with SS, and 11 high-fat diet controls, were studied. 1 H-MRS measurements at 3T and 4.7T MRI were performed on a localized voxel of the liver using PRESS sequence. Hepatic alanine (Ala), lactate+triglyceride (Lac+TG), and TG levels were compared between NASH, SS, and control groups using analysis of variance (ANOVA) tests. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolite levels and pathologic grades or NAFLD activity scores (NAS) were assessed using Pearson's correlation. RESULTS: NASH patients had higher levels of Ala (P < 0.001), Lac+TG (P < 0.001), and TG (P < 0.05) than SS patients or controls. The AUROC curve to distinguish NASH from SS was 1.00 (95% confidence interval [CI] 1.00-1.00) for Ala and 0.782 (95% CI 0.61-0.96) for Lac+TG. Ala and Lac+TG concentrations were positively correlated with steatosis grade (Ala Pearson's r = 0.723; Lac+TG r = 0.446), lobular inflammation (Ala r = 0.513), and NAS (Ala r = 0.743; Lac+TG r = 0.474). CONCLUSION: 1 H-MRS is potentially useful for noninvasive diagnosis of NASH and simple steatosis by hepatic metabolite quantification. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1298-1310.

Reduced radiation dose and improved image quality using a mini mobile digital imaging system in a neonatal intensive care unit.

This study was aimed to assess the radiation dose and image quality of a mini-mobile digital imaging (mini-DI) system for neonatal chest radiography and compared to conventional digital radiography (DR). A total of 64 neonates were examined and anatomical landmarks were assessed. The entrance surface dose of mini DI and conventional DR was 26.64±0.15 µGy and 49.11±1.46 µGy, respectively (p<0.001). The mean SNR values for mini-DI and DR were 233.2±5.1 and 31.6±1.2, and 10% MTF values were 131 and 161µm. A newly developed mini-DI is capable of preserving the diagnostic information with dose reduction in neonates under intensive care.