Light-chain amyloidosis presenting with rapidly progressive submucosal hemorrhage of the stomach

SummaryThe gastrointestinal tract is frequently in involved light-chain (AL) amyloidosis, but significant hemorrhagic complications are rare. A 71-year-old man presented to our hospital with dyspepsia and heartburn for 1 month. Gastroscopy revealed a large submucosal hematoma at the gastric fundus. Two days later, a follow-up gastroscopy indicated extensive expansion of the hematoma throughout the upper half of the stomach. The hematoma displayed ongoing expansion during the endoscopic examination, suggesting that rupture was imminent. Emergency total gastrectomy was performed, and amyloidosis was confirmed after examining the surgical specimen. Bone marrow examination revealed multiple myeloma, and serum immunoglobulin assay confirmed the diagnosis of myeloma-associated AL amyloidosis. At manuscript submission, the patient was doing well and was undergoing chemotherapy

Overexpression of hepatic serum amyloid A1 in mice increases IL-17-producing innate immune cells and decreases bone density

Serum amyloid A (SAA) is an acute-phase protein produced primarily in the liver that plays a key role in both the initiation and maintenance of inflammation. Rapidly secreted SAA induces neutrophilia at inflammatory sites, initiating inflammation and inducing the secretion of various cytokines, including TNF-α, IL-6, and IL-17. IL-17 is expressed in several inflammatory cells, including innate immune cells such as γδT cells, ILC3 cells, and neutrophils. Increased IL-17 levels exacerbate various inflammatory diseases. Among other roles, IL-17 induces bone loss by increasing receptor activator of nuclear factor-κB ligand (RANKL) secretion, which stimulates osteoclast differentiation. Several studies have demonstrated that chronic inflammation induces bone loss, suggesting a role for SAA in bone health. To test this possibility, we observed an increase in IL-17-producing innate immune cells, neutrophils, and γδT cells in these mice. In 6-month-old animals, we detected increased osteoclast-related gene expression and IL- 17 expression in bone lysates. We also observed an increase in neutrophils that secreted RANKL in the bone marrow of TG mice. Finally, we demonstrated decreased bone mineral density in these transgenic (TG) mice. Our results revealed that the TG mice have increased populations of IL-17-producing innate immune cells, γδT cells, and neutrophils in TG mice. We additionally detected increased RANKL and IL-17 expression in the bone marrow of 6-month-old TG mice. Furthermore, we confirmed significant increases in RANKL-expressing neutrophils in TG mice and decreased bone mineral density. Our results provide evidence that chronic inflammation induced by SAA1 causes bone loss via IL-17-secreting innate immune cells. © 2021 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved.1

Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small Cell Lung Carcinoma

Background/Aims: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the genesis and development of many cancers. The purpose of this study was to investigate the role of the PAK1–cyclic AMP response element-binding (CREB) axis in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms. Methods: Western blot assay and immunohistochemical staining were employed to investigate the PAK1 and CREB expression in the tissue microarray of human squamous NSCLC. Co-immunoprecipitation and immunofluorescence confocal assays were performed to determine the link between PAK1 and CREB. NSCLC xenograft models were used to study oncogenic function of PAK1 in vivo. Results: We observed that PAK1 and CREB expression levels were significantly elevated in human squamous NSCLC-tissue specimens, compared with those in adjacent normal bronchial or bronchiolar epithelial-tissue specimens, as well as their phosphorylated forms, based on western blotting. We showed in vitro that PAK1 knockdown by small-interfering RNA (siRNA) blocked CREB phosphorylation, whereas plasmid-based PAK1 overexpression resulted in CREB phosphorylation at Ser133, based on western blotting. In addition, PAK1 interacted with CREB in co-immunoprecipitation assays. Additionally, our in vitro findings detected by flow cytometry revealed that PAK1 silencing attenuated cell cycle progression, inducing apoptosis. Inhibition of PAK1 expression reduced tumor sizes and masses by modulating CREB expression and activation in xenograft models. Conclusion: These results suggest a novel mechanism whereby the PAK1–CREB axis drives carcinogenesis of squamous-cell carcinomas, and have important implications in the development of targeted therapeutics for squamous-cell lung cancer

Cloning and Characterization of the xyl1 Gene, Encoding an NADH-Preferring Xylose Reductase from Candida parapsilosis, and Its Functional Expression in Candida tropicalis

Xylose reductase (XR) is a key enzyme in d-xylose metabolism, catalyzing the reduction of d-xylose to xylitol. An NADH-preferring XR was purified to homogeneity from Candida parapsilosis KFCC-10875, and the xyl1 gene encoding a 324-amino-acid polypeptide with a molecular mass of 36,629 Da was subsequently isolated using internal amino acid sequences and 5′ and 3′ rapid amplification of cDNA ends. The C. parapsilosis XR showed high catalytic efficiency (k(cat)/K(m) = 1.46 s(−1) mM(−1)) for d-xylose and showed unusual coenzyme specificity, with greater catalytic efficiency with NADH (k(cat)/K(m) = 1.39 × 10(4) s(−1) mM(−1)) than with NADPH (k(cat)/K(m) = 1.27 × 10(2) s(−1) mM(−1)), unlike all other aldose reductases characterized. Studies of initial velocity and product inhibition suggest that the reaction proceeds via a sequentially ordered Bi Bi mechanism, which is typical of XRs. Candida tropicalis KFCC-10960 has been reported to have the highest xylitol production yield and rate. It has been suggested, however, that NADPH-dependent XRs, including the XR of C. tropicalis, are limited by the coenzyme availability and thus limit the production of xylitol. The C. parapsilosis xyl1 gene was placed under the control of an alcohol dehydrogenase promoter and integrated into the genome of C. tropicalis. The resulting recombinant yeast, C. tropicalis BN-1, showed higher yield and productivity (by 5 and 25%, respectively) than the wild strain and lower production of by-products, thus facilitating the purification process. The XRs partially purified from C. tropicalis BN-1 exhibited dual coenzyme specificity for both NADH and NADPH, indicating the functional expression of the C. parapsilosis xyl1 gene in C. tropicalis BN-1. This is the first report of the cloning of an xyl1 gene encoding an NADH-preferring XR and its functional expression in C. tropicalis, a yeast currently used for industrial production of xylitol

Fumarate-Mediated Inhibition of Erythrose Reductase, a Key Enzyme for Erythritol Production by Torula corallina

Torula corallina, a strain presently being used for the industrial production of erythritol, has the highest erythritol yield ever reported for an erythritol-producing microorganism. The increased production of erythritol by Torula corallina with trace elements such as Cu(2+) has been thoroughly reported, but the mechanism by which Cu(2+) increases the production of erythritol has not been studied. This study demonstrated that supplemental Cu(2+) enhanced the production of erythritol, while it significantly decreased the production of a major by-product that accumulates during erythritol fermentation, which was identified as fumarate by instrumental analyses. Erythrose reductase, a key enzyme that converts erythrose to erythritol in T. corallina, was purified to homogeneity by chromatographic methods, including ion-exchange and affinity chromatography. In vitro, purified erythrose reductase was significantly inhibited noncompetitively by increasing the fumarate concentration. In contrast, the enzyme activity remained almost constant regardless of Cu(2+) concentration. This suggests that supplemental Cu(2+) reduced the production of fumarate, a strong inhibitor of erythrose reductase, which led to less inhibition of erythrose reductase and a high yield of erythritol. This is the first report that suggests catabolite repression by a tricarboxylic acid cycle intermediate in T. corallina

Conceptual Study of Simulated Software Test Bench Based On Processor Emulator for Integrated Performance Verification of Satellite On-board Software

Software Test Bench should be simulated with maximum quality to real execution environment in order to verify the performance of software which is changed or newly developed. And especially faults detection and recovery are crucial function of the performance test environment. Simulated Software Test Bench based on processor emulator is attractive and can be available prior to hardware Software Test Bench if real time performance aspect is ignored. In this paper, the results of conceptual study for developing the simulated Software Test Bench are presented

Conceptual Design of On Board Digital Base Part on Satellite to Effectively Interface the Data Upon Satellite Remote Devices

In this paper, the conceptual design of satellite digital base part which is based upon data interface between satellite on-board computer and remote devices like satellite sub-components is presented. This conceptual design shows the unification of the interface between on-board computer and satellite remote devices and the hierarchical results of the interface level. A comparison of different system and merits and demerits of digital base part coming from this conceptual design is performed

Methodology to Enhance the Predictability of I/O Data Exchange Between Device and Tasks

Data coming from devices shall be transported to a specific task to be used in a software with the most accurate time and data integrity. During this process, a potential cause for invoking structured hazard and performance degradation is dormant. In this paper, a method %which can protect the situation of possible data corruption which can protect the data integrity from the possible data corruption when collision has happened during I/O data exchange between device and tasks is presented. Also, an example diagram of mechanism according to the method is shown and the effect, merits and demerits of the method is evaluated