Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI

Solitary Necrotic Nodules of the Liver Mimicking Hepatic Metastasis: Report of Two Cases

We present two cases of solitary necrotic nodules of the liver which on radiologic images mimicked hepatic metastasis. Solitary necrotic nodule of the liver is a rare but benign entity which histopathologically consists of an outer fibrotic capsule with inflammatory cells and a central core of amorphous necrotic material. The lesion was seen on contrast-enhanced CT as an ovoid-shaped hypoattenuating nodule; on CT during hepatic arteriography as enhancing nodule; on intraoperative US as a target-appearing hypoechoic nodule; on T2WI as a hyperintensity nodule, and on dynamic MR as a subtle peripheral enhancing nodule. Although the radiologic features are not specific, solitary necrotic nodule of the liver should be included in the differential diagnosis of hepatic metastasis

A novel de novo mutation in the serine-threonine kinase STK11 gene in a Korean patient with Peutz-Jeghers syndrome

BACKGROUND: Peutz-Jeghers syndrome (PJS) is an unusual autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps. Patients with PJS are at an increased risk of developing multi-organ cancer, most frequently those involving the gastrointestinal tract. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS. METHODS: Using DNA samples obtained from the patient and his family members, we sequenced nine exons and flanking intron regions of the STK11 gene using polymerase chain reaction (PCR) and direct sequencing. RESULTS: Sequencing of the STK11 gene in the proband of the family revealed a novel 1-base pair deletion of guanine (G) in exon 6 (c.826delG; Gly276AlafsX11). This mutation resulted in a premature termination at codon 286, predicting a partial loss of the kinase domain and complete loss of the C-terminal domain. We did not observe this mutation in both parents of the PJS patient. Therefore, it is considered a novel de novo mutation. CONCLUSION: The results presented herein enlarge the spectrum of mutations of the STK11 gene by identifying a novel de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS with or without a positive family history

Application of the Whole Genome-Based Bacterial Identification System, TrueBac ID, Using Clinical Isolates That Were Not Identified With Three Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Systems

Background: Next-generation sequencing is increasingly used for taxonomic identification of pathogenic bacterial isolates. We evaluated the performance of a newly introduced whole genome-based bacterial identification system, TrueBac ID (ChunLab Inc., Seoul, Korea), using clinical isolates that were not identified by three matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems and 16S rRNA gene sequencing. Methods: Thirty-six bacterial isolates were selected from a university-affiliated hospital and a commercial clinical laboratory. Species was identified by three MALDI-TOF MS systems: Bruker Biotyper MS (Bruker Daltonics, Billerica, MA, USA), VITEK MS (bioMerieux, Marcy l'Etoile, France), and ASTA MicrolDSys (ASTA Inc., Suwon, Korea). Whole genome sequencing was conducted using the Illumina MiSeq system (Illumina, San Diego, CA, USA), and genome-based identification was performed using the TrueBac ID cloud system (www.truebacid.com ). Results: TrueBac ID assigned 94% (34/36) of the isolates to known (N=25) or novel (N=4) species, genomospecies (N=3), or species group (N=2). The remaining two were identified at the genus level. Conclusions: TrueBac ID successfully identified the majority of isolates that MALDI-TOF MS failed to identify. Genome-based identification can be a useful tool in clinical laboratories, with its superior accuracy and database-driven operations.

Disproportionally Impaired Diffusion Capacity Relative to Airflow Limitation in COPD

Forced expiratory volume in 1 s (FEV₁) is a standard physiological index of chronic obstructive pulmonary disease (COPD), but reflects emphysema and vascular abnormalities less sensitively than diffusion capacity for carbon monoxide (D_LCO). This study tested whether a disproportionally impaired D_LCO relative to FEV₁ (FEV₁ z-score>-3 and D_LCO z-score≤-3) is a common functional COPD phenotype associated with distinct clinical and structural features and the prognosis of two cohorts. The cross-sectional analyses of the Korea COPD Subgroup Study (KOCOSS) cohort (multicenter study in Korea) included 743 males with COPD whose D_LCO was available. The cross-sectional and longitudinal analyses of the Kyoto University Cohort (single-center study in Japan) included 195 males with COPD who were prospectively followed for 10 years. A disproportionally impaired D_LCO relative to FEV₁ was observed in 29% and 31% of patients in the KOCOSS and Kyoto University cohorts, respectively. In the multivariable analysis, the disproportionally impaired D_LCO was associated with worse symptoms, shorter 6-minute walking distance, paraseptal and centrilobular emphysema on computed tomography, and reduced arterial oxygen and carbon dioxide pressures compared to the reference (FEV₁ z-score>-3 and D_LCO z-score>-3). In the multivariable Cox proportional hazard model, a higher long-term mortality was observed in the disproportionally impaired D_LCO group than in the reference group (hazard ratio [95% confidence interval] = 3.09 [1.52–6.29]) and similar to the D_LCO z-score≤-3 and FEV₁ z-score≤-3 group. The disproportionally impaired D_LCO relative to FEV₁ is common and associated with increased symptoms, emphysema, arterial blood gas abnormalities, and increased long-term mortality in patients with COPD