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11.
Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood 总被引:1,自引:0,他引:1
McAdow M Kim HK Dedent AC Hendrickx AP Schneewind O Missiakas DM 《PLoS pathogens》2011,7(10):e1002307
Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci--coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA)--were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans. 相似文献
12.
The endoplasmic reticulum (ER) plays essential roles indispensable for cellular activity and survival, including functions such as protein synthesis, secretory and membrane protein folding, and Ca2+ release in cells. The ER is sensitive to stresses that can lead to the aggregation and accumulation of misfolded proteins, which eventually triggers cellular dysfunction; severe or prolonged ER stress eventually induces apoptosis. ER stress-induced apoptosis causes several devastating diseases such as atherosclerosis, neurodegenerative diseases, and diabetes. In addition, the production of biopharmaceuticals such as monoclonal antibodies requires the maintenance of normal ER functions to achieve and maintain the production of high-quality products in good quantities. Therefore, it is necessary to develop methods to efficiently relieve ER stress and protect cells from ER stress-induced apoptosis. The silkworm storage protein 1 (SP1) has anti-apoptotic activities that inhibit the intrinsic mitochondrial apoptotic pathway. However, the role of SP1 in controlling ER stress and ER stress-induced apoptosis has not been investigated. In this paper, we demonstrate that SP1 can inhibit apoptosis induced by a well-known ER stress inducer, thapsigargin, by alleviating the decrease in cell viability and mitochondrial membrane potential. Interestingly, SP1 significantly blocked increases in CHOP and GRP78 expression as well as ER Ca2+ leakage into the cytosol following ER stress induction. This indicates that SP1 protects cells from ER stressinduced apoptosis by functioning as an upstream inhibitor of apoptosis. Therefore, studying SP1 function can offer new insights into protecting cells against ER stress-induced apoptosis for future applications in the biopharmaceutical and medicine industries. 相似文献
13.
Yong-Hun Park Sang Keun Ha Inwook Choi Kyu Sik Kim Jeryang Park Nakwon Choi Bumsang Kim Jong Hwan Sung 《Biotechnology and Bioprocess Engineering》2016,21(1):110-118
Transdermal drug delivery system (TDDS) may provide a more reliable method of drug delivery than oral delivery by avoiding gut absorption and first-pass metabolism, but needs a method for efficiently crossing the epidermal barrier. To enhance the delivery through the skin, we have developed a biocompatible, dissolvable microneedle array made from carboxymethyl cellulose (CMC). Using laser ablation for creating the mold greatly improved the efficiency and reduced the cost of microneedle fabrication. Mixing CMC with amylopectin (AP) enhanced the mechanical and tunable dissolution properties of the microneedle for controlled release of model compounds. Using the CMC microneedle array, we observed significant enhancement in the skin permeability of a fluorescent model compound, and also increase in the anti-oxidant activity of ascorbic acid after crossing the skin. Our dissolvable microneedle array provides a new and biocompatible method for delivery of drugs and cosmetic compounds through the skin. 相似文献
14.
Keun Soo Ahn Sung-Tae Hong Yu Na Kang Jung Hyeok Kwon Mi Jeong Kim Tae Jun Park Yong Hoon Kim Tae Jin Lim Koo Jeong Kang 《The Korean journal of parasitology》2012,50(4):357-360
A 25-year-old Uzbek male presented with right upper abdominal pain for 20 days. On radiologic studies, a huge cystic mass was noticed in the right liver which was suspected as parasitic. The patient received right hepatic segmentectomy (segment 7), and the surgically resected mass was confirmed as cystic echinococcosis (CE), measuring 10.5 cm in its diameter. The inner surface of the cyst was bile-stained. The patient was discharged on the 8th hospital day, and was rechecked 6 months after the surgical intervention without any evidence of recurrence. The present report describes findings of an imported case of CE which represented ultrasound images of the ''ball of wool''. 相似文献
15.
Bacillus subtilis SC-8 is a Gram-positive bacterium displaying narrow antagonistic activity for the Bacillus cereus group. B. subtilis SC-8 was isolated from Korean traditional fermented-soybean food. Here we report the draft genome sequence of B. subtilis SC-8, including biosynthetic genes for antibiotics that may have beneficial effects for control of food-borne pathogens. 相似文献
16.
Eun Sik Tak 《Bioscience, biotechnology, and biochemistry》2013,77(3):367-373
The coelomic cells of the earthworm consist of leukocytes, chlorogocytes, and coelomocytes, which play an important role in innate immunity reactions. To gain insight into the expression profiles of coelomic cells of the earthworm, Eisenia andrei, we analyzed 1151 expressed sequence tags (ESTs) derived from the cDNA library of the coelomic cells. Among the 1151 ESTs analyzed, 493 ESTs (42.8%) showed a significant similarity to known genes and represented 164 unique genes, of which 93 ESTs were singletons and 71 ESTs manifested as two or more ESTs. From the 164 unique genes sequenced, we found 24 immune-related and cell defense genes. Furthermore, real-time PCR analysis showed that levels of lysenin-related proteins mRNA in coelomic cells of E. andrei were upregulated after the injection of Bacillus subtilis bacteria. This EST data-set would provide a valuable resource for future researches of earthworm immune system. 相似文献
17.
18.
Hee-Jung Choi Tae-Wook Chung Mi-Ju Park Kyu Sup Lee Youngjin Yoon Hyung Sik Kim Jun Hee Lee Sang-Mo Kwon Syng-Ook Lee Keuk-Jun Kim Jin-Ho Baek Ki-Tae Ha 《PloS one》2016,11(2)
In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins β3 and β5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells. 相似文献
19.
Suji Lee Eunil Lee Man Sik Park Bo Yeon Kwon Hana Kim Dea Ho Jung Kyung Hee Jo Myung Ho Jeong Seung-Woon Rha 《PloS one》2014,9(4)
Background
The relationship between temperature and myocardial infarction has not been fully explained. In this study, we identified the threshold temperature and examined the relationship between temperature and emergency admissions due to MI in Korea.Methods
Poisson generalized additive model analyses were used to assess the short-term effects of temperature (mean, maximum, minimum, diurnal) on MI emergency visits, after controlling for meteorological variable and air pollution (PM10, NO2). We defined the threshold temperature when the inflection point showed a statistically significant difference in the regression coefficients of the generalized additive models (GAMs) analysis. The analysis was performed on the following subgroups: geographical region, gender, age (<75 years or ≥75 years), and MI status (STEMI or non-STEMI).Results
The threshold temperatures during heat exposure were for the maximum temperature as 25.5–31.5°C and for the mean temperature as 27.5–28.5°C. The threshold temperatures during cold exposure were for the minimum temperature as −2.5–1.5°C. Relative risks (RRs) of emergency visits above hot temperature thresholds ranged from 1.02 to 1.30 and those below cold temperature thresholds ranged from 1.01 to 1.05. We also observed increased RRs ranged from 1.02 to 1.65 of emergency visits when temperatures changes on a single day or on successive days.Conclusions
We found a relationship between temperature and MI occurrence during both heat and cold exposure at the threshold temperature. Diurnal temperature or temperature change on successive days also increased MI risk. 相似文献20.
See-Hyoung Park Sang Jae Noh Kyoung Min Kim Jun Sang Bae Keun Sang Kwon Sung Hoo Jung Jung Ryul Kim Ho Lee Myoung Ja Chung Woo Sung Moon Myoung Jae Kang Kyu Yun Jang 《Translational oncology》2015,8(4):239-249
BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP1), γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS), and relapse-free survival (RFS) by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001). The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents. 相似文献