Questionnaire Survey about Disaster Preparation for Users of Long-term Oxygen Therapy

Article信州医学雑誌 67(6): 407-416(2019)journal articl

The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice

Administration of heat-killed Propionibacterium acnes renders mice highly susceptible to LPS. After LPS challenge P. acnes-primed mice promptly show hypothermia, hypercoagulation (disseminated intravascular coagulation), elevation of serum proinflammatory cytokine levels, and high mortality. The surviving mice develop liver injury. As previously reported, IL-18 plays a pivotal role in the development of this liver injury. Many cell types including macrophages constitutively store IL-18 as biologically inactive precursor (pro) form. Upon appropriate stimulation exemplified by TLR4 engagement, the cells secrete biologically active IL-18 by cleaving pro-IL-18 with caspase-1. Caspase-1 is also constitutively produced as a zymogen in macrophages. Recently, NLRP3, a cytoplasmic pathogen sensor, has been demonstrated to be involved in the activation of caspase-1. Here, we review the molecular mechanisms for the liver injuries, particularly focusing on the TLR4/NLRP3-mediated caspase-1 activation process, with a brief introduction of the mechanism underlying P. acnes-induced sensitization to LPS

Effect Of Epa Ethyl Ester On Fatty Acid Profile In Hemodialysis Patients With Low Epa/Aa Ratio

BackgroundLarge amounts of n-3 polyunsaturated fatty acids are known to lower the risk of cardiovascular events (CVE). Serum eicosapentaenoic acid (EPA) / arachidonic acid (AA) ratio may potentially be a predictor of CVE which is the most common cause of death in hemodialysis (HD) patients. Therefore, we estimated the effect of EPA ethyl ester on fatty acid profile in HD patients.Subjects & MethodsFatty acid profile and high sensitivity CRP (hs-CRP) were measured in 131 patients receiving maintenance HD. Among these, 64 patients (F:M=25:39) with both low EPA/AA ratio (≦0.4) and negative CRP were enrolled in this randomized study (Group A, EPA administrated group, n=30; Group B, EPA non-administrated group, n=34). The mean age of the patients was 66.5 ± 11.9 years old and the duration of HD was 8.4 ± 7.9 years. The serum levels of EPA, AA, docosahexaenoic acid (DHA), and dihomogammalinolenic acid (DHL-A) were measured by gas chromatography (SRL, Tokyo, Japan).ResultsThe mean levels of EPA/AA ratio, DHA/AA ratio, DHL-A, non HDL-C and GNRI (Geriatric Nutritional Risk Index) were 0.28±0.13, 0.62±0.15, 22.7±8.4 μg/ml, 112.2±31.0 mg/dl and 93.6±5.5, respectively. After one month of treatment with EPA in group A, EPA/AA ratio was significantly increased (0.30±0.15 vs. 0.95±0.45, p<0.0001) and DHL-A significantly decreased (22.7±7.4 vs. 15.7±6.8, p= 0.0003), but DHA/AA ratio, serum non HDL-C and phosphate levels did not change. EPA/AA ratio was significantly higher and DHL-A lower in group A compared with group B after one month of the start of study.ConclusionsMedication of EPA for one month increases EPA/AA ratio, and decreases DHL-A level without the change of serum phosphate level in HD patients with low EPA/AA ratio

SOCS-1/SSI-1-Deficient NKT Cells Participate in Severe Hepatitis through Dysregulated Cross-Talk Inhibition of IFN-γ and IL-4 Signaling In Vivo

AbstractSuppressor of cytokine signaling-1 (SOCS-1), also known as STAT-induced STAT inhibitor-1 (SSI-1), is a negative feedback molecule for cytokine signaling, and its in vivo deletion induces fulminant hepatitis. However, elimination of the STAT1 or STAT6 gene or deletion of NKT cells substantially prevented severe hepatitis in SOCS-1-deficient mice, while administration of IFN-γ and IL-4 accelerated its development. SOCS-1 deficiency not only sustained IFN-γ/IL-4 signaling but also eliminated the cross-inhibitory action of IFN-γ on IL-4 signaling. These results suggest that SOCS-1 deficiency-induced persistent activation of STAT1 and STAT6, which would be inhibited by SOCS-1 under normal conditions, may induce abnormal activation of NKT cells, thus leading to lethal pathological changes in SOCS-1-deficient mice

The involvement of Gab1 and PI 3-kinase in β1 integrin signaling in keratinocytes

金沢大学大学院医学系研究科血管分子科学The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. β1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these β1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of β1 integrins, we established HaCaT cells with high β1integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing β1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab1 phosphorylation was also higher with high β1 integrin expression, while Shc phosphorylation was not altered. In addition, enhanced phosphatidylinositol 3-kinase activation was also observed. These observations suggest that Gab1 and phosphatidylinositol 3-kinase play pivotal roles in the β1 integrin-mediated regulation of the epidermal stem cell compartment. © 2007 Elsevier Inc. All rights reserved

Usefulness of a new DUV-LED device for the control of infection by Escherichia coli, Staphylococcus aureus, mycobacteria and spore-forming bacteria

Reliable disinfection and sterilization technologies are needed to deal with the various infectious diseases spreading around the world. Furthermore, bacteria that are difficult to eliminate by ordinary disinfection are also a problem in the medical environment. We examined the germicidal effect of a newly developed deep-ultraviolet light-emitting diode (DUV-LED) prototype device (wavelength of 280 ± 5 nm; power of 0.9 to 1.4 mW/cm2) for floor sterilization against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Mycobacterium gordonae (M. gordonae), and Bacillus subtilis (B. subtilis). This prototype device is equipped with highly practical DUV-LEDs with a high output efficiency and a long life, and was designed with consideration of the irradiation distance and the angle of the DUV-LEDs to provide a uniform irradiation rate. We found a statistically significant reduction of ≥90% in the infectious titers of both E. coli and S. aureus after irradiation for 2 s. Although acid-fast bacilli and spore-type bacilli are generally thought to be resistant to UV light irradiation compared to general bacteria, the acid-fast bacillus M. gordonae was inactivated after irradiation for 10 s, and spore-type cells of the bacillus B. subtilis were inactivated by ≥90% after irradiation for 30 s. We also found that the effects were cumulative when irradiation was performed at intervals. In the future, the usefulness of this device as an infection control measure will be evaluated in daily medical practice

Role of MSX1 in Osteogenic Differentiation of Human Dental Pulp Stem Cells

Msh homeobox 1 (MSX1) encodes a transcription factor implicated in embryonic development of limbs and craniofacial tissues including bone and teeth. Although MSX1 regulates osteoblast differentiation in the cranial bone of young animal, little is known about the contribution of MSX1 to the osteogenic potential of human cells. In the present study, we investigate the role of MSX1 in osteogenic differentiation of human dental pulp stem cells isolated from deciduous teeth. When these cells were exposed to osteogenesis-induction medium, runt-related transcription factor-2 (RUNX2), bone morphogenetic protein-2 (BMP2), alkaline phosphatase (ALPL), and osteocalcin (OCN) mRNA levels, as well as alkaline phosphatase activity, increased on days 4–12, and thereafter the matrix was calcified on day 14. However, knockdown of MSX1 with small interfering RNA abolished the induction of the osteoblast-related gene expression, alkaline phosphatase activity, and calcification. Interestingly, DNA microarray and PCR analyses revealed that MSX1 knockdown induced the sterol regulatory element-binding protein 2 (SREBP2) transcriptional factor and its downstream target genes in the cholesterol synthesis pathway. Inhibition of cholesterol synthesis enhances osteoblast differentiation of various mesenchymal cells. Thus, MSX1 may downregulate the cholesterol synthesis-related genes to ensure osteoblast differentiation of human dental pulp stem cells