Arazyme Suppresses Hepatic Steatosis and Steatohepatitis in Diet-Induced Non-Alcoholic Fatty Liver Disease-Like Mouse Model.

Arazyme, a metalloprotease from the spider Nephila clavata, exerts hepatoprotective activity in CCL4-induced acute hepatic injury. This study investigated the hepatoprotective effects in high-fat diet (HFD)-induced non-alcoholic fatty liver disease-like C57BL/6J mice. The mice were randomly divided into four groups (n = 10/group): the normal diet group, the HFD group, the arazyme group (HFD with 0.025% arazyme), and the milk thistle (MT) group (HFD with 0.1% MT). Dietary supplementation of arazyme for 13 weeks significantly lowered plasma triglyceride (TG) and non-esterified fatty acid levels. Suppression of HFD-induced hepatic steatosis in the arazyme group was caused by the reduced hepatic TG and total cholesterol (TC) contents. Arazyme supplementation decreased hepatic lipogenesis-related gene expression, sterol regulatory element-binding transcription protein 1 (Srebf1), fatty acid synthase (Fas), acetyl-CoA carboxylase 1 (Acc1), stearoyl-CoA desaturase-1 (Scd1), Scd2, glycerol-3-phosphate acyltransferase (Gpam), diacylglycerol O-acyltransferase 1 (Dgat1), and Dgat2. Arazyme directly reduced palmitic acid (PA)-induced TG accumulation in HepG2 cells. Arazyme suppressed macrophage infiltration and tumor necrosis factor α (Tnfa), interleukin-1ß (Il1b), and chemokine-ligand-2 (Ccl2) expression in the liver, and inhibited secretion of TNFα and expression of inflammatory mediators, Tnfa, Il1b, Ccl2, Ccl3, Ccl4, and Ccl5, in PA-induced RAW264.7 cells. Arazyme effectively protected hepatic steatosis and steatohepatitis by inhibiting SREBP-1-mediated lipid accumulation and macrophage-mediated inflammation.

Fournier's gangrene associated with chronic kidney disease in a dog.

A dog was diagnosed with Fournier's gangrene associated with chronic kidney disease. Clinical features included crepitant scrotal inflammation that spread to the penis; the lesion exhibited liquefactive necrosis or purulent moist gangrene. This is the first description of Fournier's gangrene associated with chronic kidney disease in a dog.

Gangrène de Fournier associée à la maladie rénale chronique chez un chien. Un diagnostic de gangrène de Fournier a été posé en association avec une maladie rénale chronique. Les caractéristiques cliniques incluaient une inflammation scrotale crépitante qui s'est propagée au pénis; la lésion a manifesté une nécrose liquéfactrice ou une gangrène humide purulente. Il s'agit de la première description de gangrène de Fournier associée à une maladie rénale chronique chez un chien.(Traduit par Isabelle Vallières).

Major repeat components covering one-third of the ginseng (Panax ginseng C.A. Meyer) genome and evidence for allotetraploidy.

Ginseng (Panax ginseng) is a famous medicinal herb, but the composition and structure of its genome are largely unknown. Here we characterized the major repeat components and inspected their distribution in the ginseng genome. By analyzing three repeat-rich bacterial artificial chromosome (BAC) sequences from ginseng, we identified complex insertion patterns of 34 long terminal repeat retrotransposons (LTR-RTs) and 11 LTR-RT derivatives accounting for more than 80% of the BAC sequences. The LTR-RTs were classified into three Ty3/gypsy (PgDel, PgTat and PgAthila) and two Ty1/Copia (PgTork and PgOryco) families. Mapping of 30-Gbp Illumina whole-genome shotgun reads to the BAC sequences revealed that these five LTR-RT families occupy at least 34% of the ginseng genome. The Ty3/Gypsy families were predominant, comprising 74 and 33% of the BAC sequences and the genome, respectively. In particular, the PgDel family accounted for 29% of the genome and presumably played major roles in enlargement of the size of the ginseng genome. Fluorescence in situ hybridization (FISH) revealed that the PgDel1 elements are distributed throughout the chromosomes along dispersed heterochromatic regions except for ribosomal DNA blocks. The intensity of the PgDel2 FISH signals was biased toward 24 out of 48 chromosomes. Unique gene probes showed two pairs of signals with different locations, one pair in subtelomeric regions on PgDel2-rich chromosomes and the other in interstitial regions on PgDel2-poor chromosomes, demonstrating allotetraploidy in ginseng. Our findings promote understanding of the evolution of the ginseng genome and of that of related species in the Araliaceae.

Interplay between 3'-UTR polymorphisms in the vascular endothelial growth factor (VEGF) gene and metabolic syndrome in determining the risk of colorectal cancer in Koreans.

BACKGROUND: Polymorphisms in angiogenesis-related genes and metabolic syndrome (MetS) risk factors play important roles in cancer development. Moreover, recent studies have reported associations between a number of 3'-UTR polymorphisms and a variety of cancers. The aim of this study was to investigate the associations of three VEGF 3'-UTR polymorphisms (1451C > T [rs3025040], 1612G > A [rs10434], and 1725G > A [rs3025053]) and MetS with colorectal cancer (CRC) susceptibility in Koreans. METHODS: A total of 850 participants (450 CRC patients and 400 controls) were enrolled in the study. The genotyping of VEGF polymorphisms was performed by TaqMan allelic discrimination assays. Cancer risks of genetic variations and gene-environment interactions were assessed by adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of multivariate logistic regression analyses. RESULTS: VEGF 1451C > T was significantly associated with rectal cancer risk (Dominant model; AOR =1.58; 95% CI = 1.09 - 2.28; p = 0.015) whereas VEGF 1725G > A correlated with MetS risk (Dominant model; AOR =1.61; 95% CI =1.06 - 2.46; p = 0.026). Of the gene-environment combined effects, the interaction of VEGF 1451C > T and MetS contributed to increased rectal cancer risk (AOR = 3.15; 95% CI = 1.74 - 5.70; p < .001) whereas the combination of VEGF 1725G > A and MetS was involved with elevated colon cancer risk (AOR = 2.68; 95% CI = 1.30 - 1.55; p =0.008). CONCLUSIONS: Our results implicate that VEGF 1451C > T and 1725G > A may predispose to CRC susceptibility and the genetic contributions may be varied with the presence of MetS.

Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors.

Recently inhibition of ROS1 kinase has proven to be a promising strategy for several indications such as glioblastoma, non-small cell lung cancer (NSCLC), and cholangiocarcinoma. Our team reported trisubstituted pyrazole-based ROS1 inhibitors by which two inhibitors showed good IC50 values in enzyme-based screening. To develop more advanced ROS1 inhibitors through SAR this trisubstituted pyrazole-based scaffold has been built. Consequently, 16 compounds have been designed, synthesized and shown potent IC50 values in the enzymatic assay, which are from 13.6 to 283 nM. Molecular modeling studies explain how these ROS1 kinase inhibitors revealed effectively the key interactions with ROS1 ATP binding site. Among these compounds, compound 9a (IC50=13.6 nM) has exerted 5 fold potency than crizotinib and exhibited high degree of selectivity (selectivity score value=0.028) representing the number of non-mutant kinases with biological activity over 90% at 10 µM.

Evolution of the large genome in Capsicum annuum occurred through accumulation of single-type long terminal repeat retrotransposons and their derivatives.

Although plant genome sizes are extremely diverse, the mechanism underlying the expansion of huge genomes that did not experience whole-genome duplication has not been elucidated. The pepper, Capsicum annuum, is an excellent model for studies of genome expansion due to its large genome size (2700 Mb) and the absence of whole genome duplication. As most of the pepper genome structure has been identified as constitutive heterochromatin, we investigated the evolution of this region in detail. Our findings show that the constitutive heterochromatin in pepper was actively expanded 20.0-7.5 million years ago through a massive accumulation of single-type Ty3/Gypsy-like elements that belong to the Del subgroup. Interestingly, derivatives of the Del elements, such as non-autonomous long terminal repeat retrotransposons and long-unit tandem repeats, played important roles in the expansion of constitutive heterochromatic regions. This expansion occurred not only in the existing heterochromatic regions but also into the euchromatic regions. Furthermore, our results revealed a repeat of unit length 18-24 kb. This repeat was found not only in the pepper genome but also in the other solanaceous species, such as potato and tomato. These results represent a characteristic mechanism for large genome evolution in plants.

Clinicoradiological Features of Pulmonary Cryptococcosis in Immunocompetent Patients.

Purpose: To assess the clinicoradiological features of pulmonary cryptococcosis in immunocompetent patients. Materials and Methods: This retrospective study included immunocompetent patients who had been diagnosed with pulmonary cryptococcosis on the histopathologic exam and underwent chest CT between January 2008 and November 2019. Imaging features were divided into major imaging patterns, distributions, and ancillary imaging findings. Univariable analysis was performed to evaluate clinicoradiological features according to the presence of serum cryptococcal antigen. Results: Thirty-one patients were evaluated (mean age: 60 years, range: 19-78 years). A single nodular lesion confined to a single lobe was the most common imaging pattern (14/31, 45.2%). Serum cryptococcal antigen tests were performed in 19 patients (19/31, 61.3%). The presence of serum cryptococcal antigen was observed in six patients (6/19, 31.6%), all of whom showed a consolidation-dominant pattern. The presence of serum cryptococcal antigen was significantly associated with the consolidation-dominant pattern compared to those associated with a nodule-dominant pattern (p = 0.011). Conclusion: A combination of CT findings of consolidation and a positive serum cryptococcal antigen test may be helpful for diagnosing pulmonary cryptococcosis in immunocompetent patients.

Structures of the γ-class carbonic anhydrase homologue YrdA suggest a possible allosteric switch.

The YrdA protein shows high sequence similarity to γ-class carbonic anhydrase (γ-CA) proteins and is classified as part of the γ-CA protein family. However, its function has not been fully elucidated as it lacks several of the conserved residues that are considered to be necessary for γ-CA catalysis. Interestingly, a homologue of γ-CA from Methanosarcina thermophila and a ß-carboxysomal γ-CA from a ß-cyanobacterium have shown that these catalytic residues are not always conserved in γ-CAs. The crystal structure of YrdA from Escherichia coli (ecYrdA) is reported here in two crystallographic forms. The overall structure of ecYrdA is also similar to those of the γ-CAs. One loop around the putative catalytic site shows a number of alternative conformations. A His residue (His70) on this loop coordinates with, or is reoriented from, the catalytic Zn(2+) ion; this is similar to the conformations mediated by an Asp residue on the catalytic loops of ß-CA proteins. One Trp residue (Trp171) also adopts two alternative conformations that may be related to the spatial positions of the catalytic loop. Even though significant CA activity could not be detected using purified ecYrdA, these structural features have potential functional implications for γ-CA-related proteins.

[Pathophysiology and Role of Coronary CT Angiography in Stable Angina]. / ì•ˆì •í˜• 협심증의 병태생리 및 관상동맥 CT í˜ˆê´€ì¡°ì˜ìˆ ì˜ ì—­í• .

The clinical concept of coronary artery disease (CAD) has seen a paradigm shift over the last decade. CAD is mostly a progressive disease, and patients with CAD can develop acute coronary syndromes at any point in disease progression. In this clinical context, a new term, "chronic coronary syndrome," was published in the 2019 European Society of Cardiology guidelines, reflecting the importance of early diagnosis and active management. Recent advances have been made in the evaluation of CAD using coronary CT angiography (CCTA). The clinical usefulness of CCTA in patients with stable angina or chronic coronary syndrome begins with the detection of early asymptomatic CAD. The characterization of atherosclerotic plaque and its role in determining treatment strategies for CAD have been demonstrated for all stages of the disease. This review describes the pathophysiology of stable angina to aid in the understanding of the clinical applications of CCTA.

Late-infantile GM1 gangliosidosis: A case report.

RATIONALE: Monosialotetrahexosylganglioside (GM1) gangliosidosis is a rare lysosomal storage disorder caused by the deficiency of ß-galactosidase. Because clinical symptoms of GM1 gangliosidosis overlap with other neurodevelopmental disorders, the diagnosis of this disease is not easy, specifically in late infantile GM1 gangliosidosis. This report described a case of late-infantile GM1 gangliosidosis mistaken for juvenile idiopathic arthritis. PATIENT CONCERNS: A 16-year-old girl was referred to our hospital due to persistent multiple joint deformities and mental retardation, which could not be explained by juvenile idiopathic arthritis. DIAGNOSIS: We made a diagnosis of late infantile GM1 gangliosidosis through enzyme assays and genetic testing after a skeletal survey. INTERVENTIONS: The patient underwent cervical domeplasty and laminectomy for cord compression and received rehabilitation treatment. OUTCOMES: The patient is receiving multidisciplinary care at a tertiary center for variable skeletal disease and conditions associated with GM1 gangliosidosis. LESSONS: Late infantile GM1 gangliosidosis should be considered in the differential diagnosis of progressive neurologic decline and skeletal dysostosis.

Predictive Value of Interstitial Lung Abnormalities for Postoperative Pulmonary Complications in Elderly Patients with Early-stage Lung Cancer.

PURPOSE: Identifying pretreatment interstitial lung abnormalities (ILAs) is important because of their predictive value for complications after lung cancer treatment. This study aimed to assess the predictive value of ILAs for postoperative pulmonary complications (PPCs) in elderly patients undergoing curative resection for early-stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Elderly patients (age ≥ 70 years) who underwent curative resection for pathologic stage I or II NSCLC with normal preoperative spirometry results (pre-bronchodilator forced expiratory volume in 1 s to forced vital capacity [FVC] ratio > 0.70 and FVC ≥ 80% of the predicted value) between January 2012 and December 2019 were retrospectively identified. Univariable and multivariable regression analyses were performed to assess risk factors for PPCs. The Kaplan-Meier method and log-rank test were used to analyze the relationship between ILAs and postoperative mortality. One-way analysis of variance was performed to assess the correlation between ILAs and hospital stay duration. RESULTS: A total of 262 patients (median age, 73 [interquartile range, 71-76] years; 132 male) were evaluated. A multivariable logistic regression model revealed that, among several relevant risk factors, fibrotic ILAs independently predicted both overall PPCs (adjusted odds ratio [OR], 4.84; 95% confidence interval [CI], 1.35-17.38; p=0.016) and major PPCs (adjusted OR, 8.72; 95% CI, 1.71-44.38; p=0.009). Fibrotic ILAs were significantly associated with higher postoperative mortality and longer hospital stay (F=5.21, p=0.006). CONCLUSION: Pretreatment fibrotic ILAs are associated with PPCs, higher postoperative mortality, and longer hospital stay.

[Mediastinal Teratoma: A Pictorial Essay]. / ì¢ ê²©ë™ ê¸°í˜•ì¢ : 임상 화보.

The mediastinum is the most prevalent site of extragonadal teratomas. Patients with mediastinal mature teratomas are usually young adults, and the condition does not show significant sexual differences. Mediastinal teratomas are mostly located in the anterior mediastinum. Patients are usually asymptomatic, although they can have several complications when the teratomas become large or rupture. Most mediastinal teratomas can be diagnosed using CT. Diagnosing ruptured or malignant teratomas is challenging because of their atypical clinical and radiological presentations. In this article, we describe various manifestations of mediastinal teratomas, with an emphasis on radiologic features.

Clinical implication of interstitial lung abnormality in elderly patients with early-stage non-small cell lung cancer.

BACKGROUND: Interstitial lung abnormality (ILA) is closely related to lung cancer. This study aimed to assess whether the presence of ILA is associated with the clinicoradiological features of elderly patients (≥70 years) with early-stage non-small cell lung cancer (NSCLC). METHODS: Elderly patients who underwent surgical resection for stage I or II NSCLC with preserved lung function between 2012 and 2019 were retrospectively identified. ILA was evaluated using a three-point scale. Univariate analyses were performed for clinicoradiological features based on the presence of ILA. Logistic and linear regression analyses were performed for cancer staging and tumor size, respectively. RESULTS: A total of 254 patients were evaluated. The presence of ILA (score = 2) was significantly associated with male sex, current or former smoker status, higher pack-years of smoking, low forced expiratory volume in one second/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide, and presence of emphysema (≥5%). Tumor characteristics, such as lower lobe and outer one-third location, squamous cell carcinoma, and higher cancer stage (stage II) were significantly associated with ILA. The presence of ILA independently predicted a higher cancer stage (adjusted odds ratio, 1.81; 95% confidence interval, 1.10-2.96; p = 0.02) and a larger tumor size in linear regression analysis (p = 0.04). CONCLUSIONS: Patients with ILA showed clinicoradiological features similar to those of idiopathic pulmonary fibrosis in elderly patients with early-stage NSCLC. Identifying the clinical implications of ILA in early-stage lung cancer will guide clinicians in providing appropriate management for these patients.

Larvicidal activity of Myrtaceae essential oils and their components against Aedes aegypti, acute toxicity on Daphnia magna, and aqueous residue.

The larvicidal activity of 11 Myrtaceae essential oils and their constituents was evaluated against Aedes aegypti L. Of the 11, Melaleuca linariifolia Sm., Melaleuca dissitiflora F. Muell., Melaleuca quinquenervia (Cav.) S. T. Blake, and Eucalyptus globulus Labill oils at 0.1 mg/ml exhibited > or = 80% larval mortality. At this same concentration, the individual constituents tested, allyl isothiocyanate, alpha-terpinene, p-cymene, (+)-limonene, (-)-limonene, gamma-terpinene, and (E)-nerolidol, resulted in > or = 95% mortality. We also tested the acute toxicity of these four active oils earlier mentioned and their constituents against Daphnia magna Straus. M. linariifolia and allyl isothiocyanate was the most toxic to D. magna. Twodays after treatment, residues of M. dissitiflora, M. linariifolia, M. quinquenervia, and E. globulus oils in water were 55.4, 46.6, 32.4, and 14.8%, respectively. Less than 10% of allyl isothiocyanate, alpha-terpinene, p-cymene, (-)-limonene, (+)-limonene, and gamma-terpinene was detected in the water at 2 d after treatment. Our results indicated that oils and their constituents could easily volatilize in water within a few days after application, thus minimizing their effect on the aqueous ecosystem. Therefore, Myrtaceae essential oils and their constituents could be developed as control agents against mosquito larvae.

[Direct MR Arthrography of the Hip: Diagnosis and Pitfalls of Acetabular Labral Lesions]. / ê³ ê´€ì ˆ ì§ì ‘ ìžê¸°ê³µëª ê´€ì ˆì¡°ì˜ìˆ : 비구순 병변의 진단 및 í•¨ì •.

Tearing of the acetabular labrum is a common cause of chronic hip pain. MR arthrography (MRA) of the hip is the imaging procedure of choice for the evaluation of acetabular labrum. Familiarity with the various imaging findings of MRA of the hip allows recognition of normal variants and differentiation from true pathologic conditions. This article comprehensively reviews the technical aspects and interpretation of MRA of the hip. The appearances of normal and abnormal labra in MRA are discussed. Potential pitfalls in labral tear interpretation, such as sulci around the hip, normal variants of the labrum and plicae, and osseocartilaginous and soft tissue lesions identified on MRA of the hip are also described.

Blastic plasmacytoid dendritic cell neoplasm of the breast: A case report and review of the literature.

RATIONALE: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon and aggressive hematologic malignancy that arises from plasmacytoid dendritic cells. BPDCN typically presents with skin lesions with or without involvement of lymph nodes, peripheral blood, or bone marrow. However, breast involvement of BPDCN is rare and there has been no report describing the radiologic features of BPDCN within breast parenchyma. PATIENT CONCERNS: We report a case of a 47-year-old woman who presented with an incidentally detected hypermetabolic breast lesion on PET/CT with concurrent right cheek plaque. DIAGNOSES: Skin biopsy was performed for the right cheek plaque. Mammography and breast ultrasonography were performed to evaluate the breast lesion. The lesion was depicted as a 2.5 cm sized focal asymmetry on mammogram and an irregular heterogeneous echoic mass within the mammary zone of the right upper outer breast. Core needle biopsy was performed for the breast lesion. Histologic diagnosis of the two lesions was BPDCN. INTERVENTIONS: The patient was treated with induction and consolidation chemotherapy and received allogenic peripheral blood stem cell transplantation. OUTCOMES: The patient remains in complete remission state without relapse at 34 months since initial diagnosis. LESSONS: This is the first case of BPDCN manifested as a breast parenchymal mass and assessed by diagnostic breast imaging tools (mammography and ultrasonography). This case report is significant for BPDCN within the breast parenchyma and presenting rare radiologic description of BPDCN.

[Invasive Ductal Carcinoma Originating from a Borderline Phyllodes Tumor in a Young Female: A Case Report]. / ì Šì€ 여성의 경계성 ì—½ìƒì¢ ì–‘ì—ì„œ 생긴 침윤성 ìœ ê´€ì•”: 증례 ë³´ê³ .

Phyllodes tumors of the breast are relatively rare fibroepithelial tumors that account for less than 1% of primary breast neoplasms. Phyllodes tumors have epithelial and stromal components and they originate from the periductal stroma. They are classified as benign, borderline, or malignant. Carcinomatous differentiation of the epithelial components of phyllodes tumors is rare, and their imaging features have not been accurately described. Herein, we report a rare case of invasive ductal carcinoma originating from a borderline phyllodes tumor in a 21-year-old female with radiologic and pathologic findings.

Tumor Seeding after Percutaneous Transthoracic Needle Biopsy of Metastatic Pulmonary Ameloblastoma.

Percutaneous transthoracic needle biopsy (PTNB) is a minimally-invasive procedure that is an indispensable tool for evaluating pulmonary lesions. Though extremely rare, tumor seeding of the pleura and chest wall can occur as a complication. Given that the breast is located anterior to the thorax, needle tracking through the breast is inevitable when PTNB is performed using the anterior approach. We describe tumor seeding of metastatic pulmonary ameloblastoma in the pectoralis muscle layer of the breast along the needle track of PTNB in a 51-year-old female presenting with a palpable lump in the right breast.

Audiologic outcomes and complications of active middle ear implantation in older adults.

BACKGROUND: A few studies have reported the use of middle ear implants (MEIs) in older adults. OBJECTIVES: To evaluate the audiologic outcomes and postoperative complications of MEIs in older adults. METHODS: This retrospective study reviewed audiologic data and medical records from a single referral centre. We identified 34 patients aged ≥65 years who underwent middle ear implantation using the Vibrant SoundbridgeTM device. Preoperative audiometric testing and postoperative aided audiometric testing were performed to evaluate the functional hearing gain at 1 year postoperatively. Patients were divided into 2 groups depending on whether they underwent explantation because of poor hearing benefit. RESULTS: Follow-up duration ranged from <1 to 5.3 years. The functional gain with MEIs significantly improved relative to the preoperative air conduction thresholds at 0.5, 1, 2, and 4 kHz. Eight patients underwent explantation and 7 lost their external audio processor devices. Those who removed their implants because of the poor hearing (group 1) showed significantly worse hearing thresholds at 1 kHz and speech discrimination scores than the others (group 2). CONCLUSIONS AND SIGNIFICANCE: MEIs for auditory rehabilitation can provide improved speech recognition and significant functional gains in older adults. Patients must be given appropriate preoperative explanations regarding the expected outcomes.