This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers.
Kim, Dae-Ran;Ahn, Sung-Wan;Park, Kyu-Sang;Kong, In-Deok
Biomedical Science Letters
/
v.13
no.2
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pp.119-125
/
2007
It is widely known that protein tyrosine kinases (PTKs) are involved in controlling many biological processes such as cell growth, differentiation, proliferation, survival and apoptosis. An $\alpha3\beta4$ subunit combination acts as a major functional acetylcholine receptor (nAChRs) in male rat major pelvic ganglion (MPG) neurons, and their activation induces fast inward currents and intracellular calcium increases. Recently it has been reported that the activity of acetylcholine receptors (AChRs) in some neurons can be negatively regulated by PTKs. However, the exact mechanism of regulation of nAChRs by PTKs is poorly understood. Therefore, we examined the potential role particular in nAChR by PTK using electrophysiology and calcium imaging in male rat MPG neurons. ACh induced inward currents and $(Ca^{2+})_i$ increases in MPG neurons, concomitantly. These responses were inhibited by more than 90% in $Na^+$- or $Ca^{2+}$- free solution. $\alpha$-conotoxin AuIB, a selective $\alpha3\beta4$ nAChR blocket, inhibited ACh-induced inward currents. Genistein (10 $\mu$M), a broad-spectrum tyrosine kinase inhibitor, markedly decreased ACh-induced currents and $Ca^{2+}$ transients, whereas 10 $\mu$M genistin, an inactive analogue, had little effect. Overall these data suggest that the activities of $\alpha3\beta4$ AChRs in MPG neurons are positively regulated by PTK. In conclusion, trosine kinase may be one of the key factors in the regulation of $\alpha3\beta4$ nAChRs in rat MPG neurons, which may play an important roles in the autonomic neuronal function such as synaptic transmission, autonomic reflex, and neuronal plasticity.
${\gamma}$-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and its actions are mediated by subtypes of GABA receptors named as $GABA_A$, $GABA_B,\;and\;GABA_C,\;GABA_A$, receptor consisting of ${\alpha},\;{\beta},\;{\gamma}\;and\;{\delta}$ subunits is a heterooligomeric ligand-gated chloride channel. This study was performed to investigate regulation of $GABA_A$ receptor by protein kinase C(PKC). Ion currents were recorded using gramicidine-perforated patch and whole cell patch clamp. mRNA encoding the subunits of PKC expressed in major pelvic ganglion (MPG) neurons was detected by using RT-PCR. The GABA-induced inward current was increased by PKC activators and decreased by PKC inhibitors, respectively. These effects were not associated with intracellular $Ca^{2+}$ and GAG (1-oleoyl-2-acetyl-sn-glycerol), a membrane permeable diacylglycerol (DAG) analogue. These results mean that the subfamily of PKC participating in activation of $GABA_A$ receptor would be an atypical PKC (aPKC). Among theses, ${\xi}$ isoform of aPKC was detected by RT-PCR. Taking together, we suggest that excitable $GABA_A$ receptor in sympathetic MPG neuron seemed to be regulated by aPKC, particular in ${\xi}$ isoform. The regulatory roles of PKC on excitatory $GABA_A$ receptors in sympathetic neurons of MPG may be an important factor to control the functional activity of various pelvic organs such as bowel movement, micturition and erection.
Extracellular ATP elicits diverse physiological effects by binding to the G-protein-coupled P2Y receptors on the plasma membrane. In addition to the short-term effects of extracellular nucleotides on cell functions, there is evidence that such purinergic signalling can have long-term effects on cell proliferation, differentiation and death. The 3T3-L1 cell line derived from mouse embryo is a well-established and commonly utilized in vitro model for adipocytes differentiation and function. However, the distributions and roles of P2Y subtypes are still unknown in the preadipocyte. In this study, we identified the distributions and roles of P2Y subtypes in preadipocyte using $Ca^{2+}$ imaging and realtime PCR. ATP increased the $[Ca^{2+}]_i$ in a concentration-dependent manner. ATP increased $Ca^{2+}$ in absence and/or presence of extracellular $Ca^{2+}$. Suramin, non-selective P2Y blocker, largely blocked the ATP-induced $Ca^{2+}$ response. U73122, a PLC inhibitor, completely inhibited $Ca^{2+}$ mobilization in 3T3-L1 cells. The mRNA expression by realtime PCR of P2Y subtypes was $P2Y_2:P2Y_5:P2Y_6=1.0:12.5:0.3$. In conclusion, we showed that $P2Y_5$ receptor is a dominant purinergic receptor in preadipocytes, and multiple P2Y receptors could involve in differentiation and migration via regulating of intracellular calcium concentration.
Hoxc8 is one of the homeotic developmental control genes regulating the expression of many downstream target genes, through which animal body pattern is established during embryonic development. In previous proteomics analysis, proliferating cell nuclear antigen (PCNA) which is also known as cyclin, has been implied to be regulated by Hoxc8 in F9 murine embryonic teratocarcinoma cell. When the 5' upstream region of PCNA was analyzed, it turned out to contain 20 Hox core binding sites (ATTA) in about 1.17 kbp (kilo base pairs) region ($-520{\sim}-1690$). In order to test whether this region is responsible for Hoxc8 regulation, the upstream 2.3 kbp fragment of PCNA was amplified through PCR and then cloned into the pGL3 basic vector containing a luciferase gene as a reporter. When the luciferase activity was measured in the presence of effector plasmid (pcDNA : c8) expressing murine Hoxc8, the PCNA promoter driven reporter activity was reduced. To confirm whether this reduction is due to the Hoxc8 protein, the siRNA against Hoxc8 (5'-GUA UCA GAC CUU GGA ACU A-3' and 5'-UAG UUC CAA GGU CUG AUA C-3') was prepared. Interestingly enough, siRNA treatment up regulated the luciferase activity which was down regulated by Hoxc8, indicating that Hoxc8 indeed regulates the expression of PCNA, in particular, down regulation in NIN3T3 cells. These results altogether indicate that Hoxc8 might orchestrate the pattern formation by regulating PCNA which is one of the important proteins involved in several processes such as DNA replication and methylation, chromatin remodeling, cell cycle regulation, differentiation, as well as programmed cell death.
This study was performed in order to evaluate the risk factors for nosocomial urinary tract infection and the frequencies of organisms isolated, and to provide the epidemiologic and basic data of hospital acquired urinary tract infection in intensive care unit. A prospective analysis was performed with 1,235 urine samples following urinary bladder catheterization in 569 patients, who had no evidence of UTI at the time of catheter insertion, admitted to intensive care unit in Pusan P hospital between June 1997 and May 1998. To identify risk factors for UTI, clinical characteristics of infected patients were analyzed. We analyzed these data by percentage, chi-square and odd ratio. Obtained results were as follows: A total of 569 patients (male 341 and female 228) were an average age of 50.8 years and catheterization of 8.04 days. Incidence of UTI was 16.1% (199/1,235) and The risk factors of UTI were duration of catheterization over 7 days, no use of systemic antibiotics, summer and female, and During the first 7 days these risk factors were no use of systemic antibiotics, summer, place of first catheter insertion (ICU) and type of intensive care unit (NSICU). A total of 220 the isolated strains were Gram negative rod 83 (37.7%), yeast like fungi 74 (33.6%) and Gram positive cocci 63 (28.6%). The common organisms isolated were Enterococcus faecalis 23 (10.5%), Serratia marcescens 19 (8.6%), Pseudomonu spp.17 (7.7%), E. ooh 16 (7.3%), Staphylococcus epidemidis 11 (5.0%) mdklebsiellapneumoniae 8 (3.6%). Therefore, in these results 199 of 569 (35%) patients in ICU with indwelling urinary catheter developed UTI. The risk factors for UTI are prolonged duration of catheterization, no use of systemic antibiotics, summer, and female.
Kim, You-Sun;Kokturk, Nurdan;Kim, Ji-Young;Lee, Sei Won;Lim, Jaeyun;Choi, Soo Jin;Oh, Wonil;Oh, Yeon-Mok
Molecules and Cells
/
v.39
no.10
/
pp.728-733
/
2016
Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models. The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously. In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs. Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs). Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs. Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection. The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14. A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs. Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection. These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke. These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.
In this study, we use data from the 2021 National Health and Nutrition Examination Survey to determine the relationship between oral health and depression in Korean adults and provide basic data to prevent oral diseases that affect depression. The final subjects of the study were 5,952 adults aged 19 or older among the 7,090 subjects who responded to the survey in the 3rd year of the 8th period (2021), and the total frequency discrepancy in the research results was omitted due to missing values. Complex sample logistic regression analysis was performed to confirm the relationship between oral health and depression. Depression according to general characteristics depends on gender (P < 0.001), number of household members (P = 0.047), and subjective health level (P < 0.001). Depression according to oral characteristics was statistically significant for complaints of chewing discomfort (P = 0.006) and toothache within the past year (P = 0.023). As a result of analyzing factors affecting depression, in terms of gender, men are 0.43 times more likely than women (95% CI: 0.28~0.65), and in terms of subjective health level, good compared to bad is 0.46 times more likely (95% CI: 0.28~0.75), the average was 0.59 times (95% CI: 0.40~0.87) higher, which was statistically significant. Therefore it seems necessary to improve mental health such as depression in order to relieve oral discomfort and to motive people to take responsibility for won health through oral health education programs related to oral health to oral health related to oral health and mental health.
Among all subjects who participated in the survey in the 9th 1st year (2022), 2,448 men (44.0%) and 3,166 women (56.0%) aged 12 or older were identified to determine oral care behavior according to orthodontic treatment experience. The purpose was to provide basic data on the oral care of patients wearing orthodontic appliances. 1. When it comes to brushing teeth, brushing before going to bed was the highest. Regarding the use of oral care products, 3,965 people (69.1%) said they 'do not use dental floss', 4,064 people (73.2%) said they 'do not use interdental brushes', and 4,064 people (73.2%) said they used oral rinse. 'I don't do it' was the highest at 4,417 (77.7%), and electric toothbrushes were the highest at 'I don't do it' at 5,241 (93.6%). 2. In terms of the effect of orthodontic treatment experience on toothbrushing time, with orthodontic treatment experience, toothbrushing after breakfast was 0.598 times more likely (P<0.001), and toothbrushing after lunch was 1.482 times more likely (P<0.001). Toothbrushing after dinner was 0.805 times higher (P=0.049), and toothbrushing before going to bed was 1.794 times higher (P<0.001), which was statistically significant. 3. When having orthodontic treatment experience, dental floss was found to be used 1.434 times more often (P=0.002), interdental brushes were used 1.464 times more times (P<0.001), and oral rinses were found to be used 1.457 times more times (P=0.002), which was statistically significant.
Kim, You-Sun;Kim, Ji-Young;Huh, Jin Won;Lee, Sei Won;Choi, Soo Jin;Oh, Yeon-Mok
Tuberculosis and Respiratory Diseases
/
v.78
no.3
/
pp.239-245
/
2015
Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only $5{\times}10^4$ MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.
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