• BMB Reports
• /
• 제49권3호
• /
• pp.137-138
• /
• 2016

Satiety cues a feeding animal to cease further ingestion of food, thus protecting it from excessive energy gain. Impaired control of satiety is often associated with feeding-related disorders such as obesity. In our recent study, we reported the identification of a neural pathway that expresses the myoinhibitory peptide (MIP), critical for satiety responses in Drosophila. Targeted silencing of MIP neuron activity strikingly increased the body weight (BW) through elevated food intake. Similarly, genetic disruption of the gene encoding MIP also elevated feeding and BW. Suppressing the MIP pathway behaviorally transformed the satiated flies to feed similar to the starved ones, with augmented sensitivity to food. Conversely, temporal activation of MIP neuron markedly reduced the food intake and BW, and blunted the sensitivity of the starved flies to food as if they have been satiated. Shortly after termination of MIP neuron activation, the reduced BW reverted to the normal level along with a strong feeding rebound. Together our results reveal the switch-like role of the MIP pathway in feeding regulation by controlling satiety.

• Mycobiology
• /
• 제42권2호
• /
• pp.152-157
• /
• 2014

The iron uptake and utilization pathways play a critical role in allowing human pathogens, including Cryptococcus neoformans, the causative agent of fatal meningoencephalitis, to survive within the mammalian body by competing with the host for iron. Here we show that the iron regulon is also required for diverse environmental stress responses and that in C. neoformans, it is regulated by the high-osmolarity glycerol response (HOG) pathway. Between CFO1 and CFO2, two ferroxidase genes in the iron regulon, CFO1 but not CFO2 was induced during oxidative and osmotic stress. Interestingly, we found that the HOG pathway repressed basal expression of both CFO1 and CFO2. Furthermore, when the HOG pathway was blocked, CFO2 also responded to oxidative and osmotic stress and the response of CFO1 was increased. We also established that CFO1 plays a major role in responding and adapting to diverse environmental stresses, including oxidative and genotoxic damage, osmotic fluctuations, heavy metal stress, and stress induced by cell membrane destabilizers. Therefore, our findings indicate that in C. neoformans, the iron uptake and utilization pathways are not only required for iron acquisition and survival, but also play a significant role in the environmental stress response through crosstalk with the HOG pathway.

• Journal of Microbiology
• /
• 제34권2호
• /
• pp.158-165
• /
• 1996

The signal transduction pathways through the RAS gene product and adenyl cyclease play a critical role in regulation of the cell cycle in yeast, Saccharomyces cerevisiae. We examined the genetic relationship between the spt3 gene and ras/cAMP pathway. A mutation in the SPT3 gene suppressed cell cycle arrest at the G1 phase caused by either an inactivation of the RAS or CYR1 gene which encodes a yeast homologue of human ras proto-oncogene or adenyl cyclase, respectively. The phenotypes such as sporulation and heat shock resistancy, that resulted from a partial inactivation of the RAS or CYR1 genes, were also suppressed by the spt3 mutation. Expression of the SSA1 gene encoding one of th heat shock proteins (Hsp70) can be induced by heat shock or nitrogen starvation. Expression of this gene is derepressed in cry1-2 and spt3 mutants. The bcy 1 mutation repressed by the bcy1 mutation, but not in spt3 mutants. These results suggest that the SPT gene is involved in expression of genes that are affected by the RAS/cAMP pathway.

• 대한한방부인과학회지
• /
• 제35권1호
• /
• pp.75-90
• /
• 2022

Objectives: The purpose of this study protocol is firstly to investigate the status of Korean medical treatment of dysmenorrhea, and secondly to investigate effectiveness of the Clinical Pathway (CP) of dysmenorrhea and review the applicability. Methods: This is a multi-center observational study. The data will be prospectively collected from 14 Korean medicine clinics. 45 patients for each of the CP-applied and non-applied groups will be recruited to compare the degree of improvement in menstrual pain. All the diagnosis records, treatment methods, treatment results, adverse events, and medical expenses of patients with dysmenorrhea will be collected. We will investigate the proportion of patients who could be applied with CP, and the actual number of CP applications, and CP completion rate to evaluate the applicability. Additionally, the satisfaction survey will be used to collect feedback from medical staff members and patients. Results: The results of this study will be disseminated through peer-reviewed publications and scientific presentations. Conclusions: This study is expected to provide valuable data for application of standard Korean medicine clinical pathway for dysmenorrhea.

• 간호행정학회지
• /
• 제7권2호
• /
• pp.265-284
• /
• 2001

The case management has been applied to improve the quality of care and the cost-effectiveness in the most health care institutions. In a way of case management, the critical pathway(CP) has been executed in many acute care settings, focused on the diagnoses with high cost, high volume, and high risk. This study was conducted to develop a case management program using CP as an intervention of patients with lumbar spinal stenosis for the surgery of posterolateral fusion, and to find out the effects of the critical pathway on the quality of nursing care, patient satisfaction as an outcome of care, length of stay and medical charge, and nurses' job satisfaction. At the same time, patients' functional states were checked with the Oswestry Low Back Pain Index, to show that the CP would not decrease the patients' function compared to the control group. The subjects were 25 control patients with a usual operation of lumbar fusion and 25 experimental patients with CP. They were all female, aged $50s{\sim}70s$, admitted in the Orthopedic surgery ward of a university hospital. Also nurses on the floor using CP were asked to respond to measurement tool of job satisfaction before and after the application of CP, and compared with other nurses on the different wards. Data were analyzed with t-test for continuous variables and chi-square for non-parametric variables in addition to the reliability test of the measurement tools. The results of this study were as followings: 1. Patients' functional states The differences in Oswestry scores of the experimental and control groups assessed at preoperation and at discharge were not statistically significant. The change in scores of the experimental group measured at preoperation and at discharge was larger than that of the control group, however the difference was not statistically significant. The results indicate that the CP did not decrease the patients' functional status. 2. The quality of nursing care The total of quality of nursing care given to the experimental group was better than that of the control group(P=.000). In addition, the experimental group showed better scores of quality of every item of care than the control group(P=.000 -.004). 3. Patient satisfaction Patients of the experimental group were not more satisfied with general care than the control group. But they were more satisfied with discharge care of 'explanation about medication, body posture, and brace application' and 'explanation about the adjustment of daily living and exercise during recovery'(P= .047, P=.028). 4. Nurses' job satisfaction Nurses working with the CP showed more job satisfaction than before the CP introduction(P=.048). But the control group of nurses on a different floor showed no change in job satisfaction at the same period of time. 5. Length of stay and medical charge The mean length of stay of the experimental group was shorter than that of the control group without statistical significance. The charge of medication and treatment of the experimental group were smaller than that of the control group(P=.011, P=.000). The results of the study support that the case management using critical pathway enables to improve the quality of care and job satisfaction, to reduce the medical charge, and consequently to increase satisfaction with care. However, the case management should be instituted focusing on the quality improvement of nursing and the client satisfaction, not just for the purpose of cost-effectiveness of health care facilities.

• Journal of Trauma and Injury
• /
• 제25권4호
• /
• pp.159-165
• /
• 2012

Purpose: For trauma patients, an early-transport and an organized process which are not delayed in hospital stage are necessary. Our hospital developed a procedure, the trauma Critical Pathway (CP), through which a traumatic patient has the priority over other patients, which makes the diagnostic and the therapeutic processes faster than they are for other patients. Methods: The records of patients to whom Trauma CP were applied from January 1, 2011 through April 15. 2012. were reviewed. We checked several time intervals from ER visiting to decision of admission-department, to performing first CT, to applying angio-embolization, to starting emergency operation and to discharging from ER. In addition, outcomes such as duration of ICU stay, hospital stay and mortality were checked and analyzed. Results: The trauma CP was applied to a total of 143 patients, of whom, 48 patients were excluded due to pre-hospital death, ER death, transferring to other hospital and not severe injury. Thus 95 patients (male 64, 67.3%) were enrolled in this study. Fifty-nine patients(62.1%) were injured by the traffic accident. The mortality rate was 10.5% and the mean Revised Trauma Score (RTS) of the patients was $6.4{\pm}2.0$. After visiting ER, decision making for admission was completed, on average, in 3 hours 10 seconds. The mean time intervals for the first CT, angio-embolization, surgery and discharge were 1 hour 20 minutes, 5 hours 16 minutes, 7 hours 26 minutes and 6 hours 13 minutes, respectively. Conclusion: The trauma CP did not show the improvement of time interval outcome, as well as mortality rate. However, this test did show that the trauma CP might be able to reduce delays in procedures for managing trauma patients at the university-based hospitals. To find out the benefit of CP protocol, a large scaled data is required.

• The Korean Journal of Physiology and Pharmacology
• /
• 제26권4호
• /
• pp.239-253
• /
• 2022

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

• Molecules and Cells
• /
• 제41권4호
• /
• pp.282-289
• /
• 2018

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T helper 17 cells and is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as a primary risk factor of COPD. However, the interaction between CS and IL-17A and the underlying molecular mechanisms have not been clarified. In the current study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A-induced IL-8 production in human bronchial epithelial cells, and sought to identify the underlying molecular mechanisms. IL-8 production was significantly enhanced following treatment with both IL-17A and CSE, while treatment with either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE increased the transcription of IL-17RA/RC and surface membrane expression of IL-17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$) via the PI3K/Akt pathway. Blockade of $GSK-3{\beta}$ inactivation by overexpression of constitutively active $GSK-3{\beta}$ (S9A) completely suppressed the CSE-induced up-regulation of IL-17R expression and the CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of $GSK-3{\beta}$ via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R, which contributes to the enhancement of IL-17A-induced IL-8 production.

• Genomics & Informatics
• /
• 제7권4호
• /
• pp.203-207
• /
• 2009

The target of rapamycin (TOR) signaling pathway conserved from yeast to human plays critical roles in regulation of eukaryotic cell growth. It has been shown that TOR pathway is involved in several cellular processes, including ribosome biogenesis, nutrient response, autophagy and aging. However, due to the functional diversity of TOR pathway, we do not know yet some key effectors of the pathway. To find unknown effectors of TOR signaling pathway, we took advantage of a green fluorescent protein (GFP)-tagged collection of budding yeast Saccharomyces cerevisiae. We analyzed protein abundance changes by measuring the GFP fluorescence intensity of 4156 GFP-tagged yeast strains under inhibition of TOR pathway. Our proteomic analysis argues that 83 proteins are decreased whereas 32 proteins are increased by treatment of rapamycin, a specific inhibitor of TOR complex 1 (TORC1). We found that, among the 115 proteins that show significant changes in protein abundance under rapamycin treatment, 37 proteins also show expression changes in the mRNA levels by more than 2-fold under the same condition. We suggest that the 115 proteins indentified in this study may be directly or indirectly involved in TOR signaling and can serve as candidates for further investigation of the effectors of TOR pathway.

• Molecules and Cells
• /
• 제41권8호
• /
• pp.762-770
• /
• 2018

Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced $I{\kappa}B{\alpha}$ degradation, $NF-{\kappa}B$ nuclear translocation, and $TNF-{\alpha}$ production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced $I{\kappa}B{\alpha}$ degradation, and heated gAd was unable to degrade $I{\kappa}B{\alpha}$, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative $IKK{\beta}$ ($DN-IKK{\beta}$) or DN-Akt overexpression blocked gAd-induced $I{\kappa}B{\alpha}$ degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the $I{\kappa}B/NF-{\kappa}B$ and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the $I{\kappa}B/NF-{\kappa}B$ pathway, and IRAK-1 downregulation, respectively.