Compared to other cancers affecting women, breast cancer is significantly associated with alcohol consumption. However, the principles underlying the carcinogenesis of alcohol-induced breast cancer ...and the related metastatic mechanisms have yet to be established. To observe the effect of alcohol on the growth regulation in breast cancer cells, we identified differentially expressed proteins in alcohol-exposed human breast cancer T47D cells using gel-based proteomics analysis. The expression of c-ros receptor tyrosine kinase (ROS1) was increased and activated by autophosphorylation, thereby activating mitogen- and stress-activated protein kinase 1 (MSK1) through the mitogen‑activated protein kinase (MAPK) pathway; activated MSK1, in turn, phosphorylated histone 3 serine 10 (H3S10p) residues in the nucleus. The increase in H3S10 phosphorylation consequently increased the level of expression of immediate-early gene such as c-fos. This study demonstrated that when breast cancer cells are exposed to alcohol, phosphorylated ROS1 activates MSK1 via Erk1/2 in the MAPK pathway, which then induces modifications to histone residues that regulate gene expression by 14-3-3 protein recruitment, leading to a lack of control of breast cancer cell proliferation.
Purpose: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP ...antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. Methods: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. Results: The RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020). Conclusions: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.
We cloned the gene for an extracellular α-amylase, AmyE, from the hyperthermophilic bacterium Thermotoga neapolitana and expressed it in Escherichia coli. The molecular mass of the enzyme was 92 kDa ...as a monomer. Maximum activity was observed at pH 6.5 and temperature 75°C and the enzyme was highly thermostable. AmyE hydrolyzed the typical substrates for α-amylase, including soluble starch, amylopectin, and maltooli-gosaccharides. The hydrolytic pattern of AmyE was similar to that of a typical α-amylase; however, unlike most of the calcium (Ca^sup 2+^)-dependent α-amylases, the activity of AmyE was unaffected by Ca^sup 2+^. The specific activities of AmyE towards various substrates indicated that the enzyme preferred maltooligosaccharides which have more than four glucose residues. AmyE could not hydrolyze maltose and maltotriose. When maltoheptaose was incubated with AmyE at the various time courses, the products consisting of maltose through maltopentaose was evenly formed indicating that the enzyme acts in an endo-fashion. The specific activity of AmyE (7.4 U/mg at 75° C, pH 6.5, with starch as the substrate) was extremely lower than that of other extracellular α-amylases, which indicates that AmyE may cooperate with other highly active extracellular α-amylases for the breakdown of the starch or α-glucans into maltose and maltotriose before transport into the cell in the members of Thermotoga sp.PUBLICATION ABSTRACT
PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus ...gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-beta-(Abeta-) induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection of Abeta.sub.25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of Abeta expression and activation of microglia and astrocytes in the Abeta.sub.25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Abeta-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD.
Background: The standardized autonomic function test has become widely available. However, there are no reference data for this test for the Korean population. This study explored reference data for ...sudomotor and cardiovagal function tests for the Korean population. Methods: The sweat volume by quantitative sudomotor axon reflex test, heart-rate response to deep breathing (HRdb), expiration:inspiration (E:I) ratio, and Valsalva ratio (VR) were measured in 297 healthy Korean volunteers aged from 20 to 69 years. Multivariate regression analysis was performed to evaluate the effects of age, sex, and body mass index on these variables. The 2.5th, 5th, 10th, 90th, 95th, and 97.5th percentile values were obtained for each investigation. Results: The sweat volume was higher in males than in females. The HRdb and E:I ratio were negatively correlated with age, and were higher in males than in females. The VR was negatively correlated with age, but it was not correlated with sex. Conclusions: This study has provided data on the reference ranges for sudomotor and cardiovagal function tests in healthy Korean adults.
Follicular bronchiolitis is an uncommon bronchiolar disorder that is characterized by the presence of hyperplastic lymphoid follicles with reactive germinal centers. The condition is associated with ...connective tissue diseases such as rheumatoid arthritis, Sjogren`s syndrome, and immunodeficiency disorders. A 56-year-old man with rheumatoid arthritis was admitted to hospital with a progressively enlarging pulmonary nodule in the left upper lobe. A follow-up contrast tomography scan showed that the nodule had increased in size from 4.2 mm to 6.3 mm over a 3 month period. An open lung biopsy was performed to establish a definite pathologic diagnosis of the pulmonary nodule, which was suspected to be a lung malignancy. The nodule was diag-nosed as follicular bronchiolitis based on the histopathology findings. We describe a patient with follicular bronchiolitis that was confirmed by an open lung biopsy, and is believed to have had rheumatoid involvement. (J Rheum Dis 2016;23:392-395)
Bacterial lipoproteins are known to be diacylated or triacylated and activate mammalian immune cells via Toll-like receptor2/6 or 2/1 heterodimer. Because the genomes of low G+C content Gram-positive ...bacteria, such as Staphylococcusaureus, do not contain Escherichiacoli-type apolipoprotein N-acyltransferase, an enzyme converting diacylated lipoproteins into triacylated forms, it has been widely believed that native lipoproteins of S.aureus are diacylated. However, we recently demonstrated that one lipoprotein SitC purified from S.aureus RN4220 strain was triacylated. Almost simultaneously, another group reported that another lipoprotein SA2202 purified from S.aureus SA113 strain was diacylated. The determination of exact lipidated structures of S.aureus lipoproteins is thus crucial for elucidating the molecular basis of host-microorganism interactions. Toward this purpose, we intensively used MS-based analyses. Here, we demonstrate that SitC lipoprotein of S.aureus RN4220 strain has two lipoprotein lipase-labile O-esterified fatty acids and one lipoprotein lipase-resistant fatty acid. Further MS/MS analysis of the lipoprotein lipase digest revealed that the lipoprotein lipase-resistant fatty acid was acylated to alpha -amino group of the N-terminal cysteine residue of SitC. Triacylated forms of SitC with various length fatty acids were also confirmed in cell lysate of the RN4220 and TritonX-114 phase in three other S.aureus strains, including SA113 strain and one Staphylococcusepidermidis strain. Moreover, four other major lipoproteins including SA2202 in S.aureus strains were identified as N-acylated. These results strongly suggest that lipoproteins of S.aureus are mainly in the N-acylated triacyl form. The determination of exact lipidated structures of Staphylococcus aureus lipoproteins is crucial for elucidating the molecular basis of the interaction of host microorganisms. Based on analytical data of lipoprotein lipase treatment and tandem mass spectrometry (MS/MS), we demonstrate that major lipoproteins of S. aureus are mainly in the N-acylated triacyl form, suggesting that S. aureus has an unidentified enzyme catalyzing N-acylation of diacylated lipoproteins. <mediaResourc e href="FEBS_7990_f1ga.gif" alt="image" mimeType="image/gif" rendition="webOriginal"/>
Bacterial lipoproteins are known to be diacylated or triacylated and activate mammalian immune cells via Toll-like receptor2/6 or 2/1 heterodimer. Because the genomes of low G+C content Gram-positive ...bacteria, such as Staphylococcusaureus, do not contain Escherichiacoli-type apolipoprotein N-acyltransferase, an enzyme converting diacylated lipoproteins into triacylated forms, it has been widely believed that native lipoproteins of S.aureus are diacylated. However, we recently demonstrated that one lipoprotein SitC purified from S.aureus RN4220 strain was triacylated. Almost simultaneously, another group reported that another lipoprotein SA2202 purified from S.aureus SA113 strain was diacylated. The determination of exact lipidated structures of S.aureus lipoproteins is thus crucial for elucidating the molecular basis of host-microorganism interactions. Toward this purpose, we intensively used MS-based analyses. Here, we demonstrate that SitC lipoprotein of S.aureus RN4220 strain has two lipoprotein lipase-labile O-esterified fatty acids and one lipoprotein lipase-resistant fatty acid. Further MS/MS analysis of the lipoprotein lipase digest revealed that the lipoprotein lipase-resistant fatty acid was acylated to α-amino group of the N-terminal cysteine residue of SitC. Triacylated forms of SitC with various length fatty acids were also confirmed in cell lysate of the RN4220 and TritonX-114 phase in three other S.aureus strains, including SA113 strain and one Staphylococcusepidermidis strain. Moreover, four other major lipoproteins including SA2202 in S.aureus strains were identified as N-acylated. These results strongly suggest that lipoproteins of S.aureus are mainly in the N-acylated triacyl form. The determination of exact lipidated structures of Staphylococcus aureus lipoproteins is crucial for elucidating the molecular basis of the interaction of host microorganisms. Based on analytical data of lipoprotein lipase treatment and tandem mass spectrometry (MS/MS), we demonstrate that major lipoproteins of S. aureus are mainly in the N-acylated triacyl form, suggesting that S. aureus has an unidentified enzyme catalyzing N-acylation of diacylated lipoproteins.
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