Jun, Jin Hyun;Kim, Jihyun;Kim, Kyung Tae;Sung, Ho Joong
Biomedical Science Letters
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v.20
no.3
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pp.180-184
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2014
Mitochondria play a crucial role in many essential biological events by way of the electron transport chains and intermembrane proteins that they contain. Abnormalities in the mitochondria are strongly correlated with the development of diseases such as atherosclerosis, cancer, and diabetes. However, the study of mitochondria has been referred to as 'labor-intensive' because of the difficulty in isolating the organelles from their various sources, which can include cultured cells and tissues. Multiple companies provide mitochondria isolation kits, and it is possible for investigators to use different kits and apply different protocols depending on the source of the mitochondria. Therefore, we focused on producing an isolation buffer that could be applied to both cultured cells and tissues, and optimized an isolation protocol that could be used with both. Specifically, we adjusted the buffer condition that can be applied to human cervical cancer cells, fibroblasts, and tissues such as mouse liver and spleen. We also optimized the protocol to improve the efficacy and efficiency of the steps involved in the isolation of mitochondria. These methodological improvements may contribute to advanced research by allowing investigators to overcome the difficulties involved in isolation of mitochondria from biological samples.
Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.
This study purports to investigate the determinant of job satisfaction among workers working at Long-term care hospitals. The independent variables contain three groups of determinants: organizational characteristics variables(job autonomy, job variety, distributive justice, role conflict, supervisor support, job suitability, job significance, job security, organizational support, job growth, promotional opportunity), environmental variables(job opportunity), and psychological variables (met expectation, job efficacy, positive affectivity, and negative affectivity). The sample used in this study consisted of 250 workers from 4 Long-term care hospitals nationwide. Data were collected with self-administered questionnaires and analyzed using multiple regression analysis. The results of the study are as follows: 1) the following variables, listed in order of size, have significant effects on job satisfaction: negative affectivity(-), job significance(+), job growth(+), age(+), positive affectivity(+), organizational support(+), job opportunity(-). 2) the variance of job satisfaction explained by the variables used in the study are 53.8%. When demographic variables added to Model I, job satisfaction explained by variables are 55.4%. 3) the results of this study indicate that three variables of negative affectivity, job significance, job growth are especially important for improving the level of job satisfaction among workers at Long-term care hospitals.
DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related kinase family is a well-known player in repairing DNA double-strand break through non-homologous end joining pathway. This mechanism has allowed us to understand its critical role in T and B cell development through V(D)J recombination and class switch recombination, respectively. We have also learned that the defects in these mechanisms lead to the severely combined immunodeficiency (SCID). Here we highlight some of the latest evidence where DNA-PKcs has been shown to localize not only in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. While it is an exciting time to unveil novel functions of DNA-PKcs, one should carefully choose experimental models to study DNA-PKcs as the experimental evidence has been shown to differ between cells of defective DNA-PKcs and those of DNA-PKcs knockout. Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in an attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level.
Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.
A Convergence study was conducted to investigate the factors influencing the burnout in caregivers and to present a strategy for effective program development. The subjects of this study were 185 caregivers who had worked for 6 months in a G city Nursing facility and distributed the self-reported questionnaire in September 2015. Data were analyzed using t-test, one-way ANOVA, $Scheff{\acute{e}}$ test, Pearson's correlation coefficient and Stepwise multiple regression analysis were performed. According to the results, the identified influencing factors were stress of personal role and daily work factors(${\beta}=.307$, p<.001), stress of relationship with supervisors(${\beta}=.186$, p<.021), confidence(${\beta}=.182$, p<.005), passive coping(${\beta}=.140$, p<.035) with burnout in caregivers. The explanatory power($R^2$) by 4 variables was 27.5%. Based on the results of this study, it would be necessary to develop an burnout reduction program that can reduce stress, increase self-confidence, and diversify coping strategies in order to reduce burnout of caregivers.
Shibo Wei;Yan Zhang;Baeki E. Kang;Wonyoung Park;He Guo;Seungyoon Nam;Jong-Sun Kang;Jee-Heon Jeong;Yunju Jo;Dongryeol Ryu;Yikun Jiang;Ki-Tae Ha
BMB Reports
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v.57
no.6
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pp.287-292
/
2024
Hepatocellular Carcinoma (HCC), the predominant primary hepatic malignancy, is the prime contributor to mortality. Despite the availability of multiple surgical interventions, patient outcomes remain suboptimal. Immunotherapies have emerged as effective strategies for HCC treatment with multiple clinical advantages. However, their curative efficacy is not always satisfactory, limited by the dysfunctional T cell status. Thus, there is a pressing need to discover novel potential biomarkers indicative of T cell exhaustion (Tex) for personalized immunotherapies. One promising target is Cyclin-dependent kinase inhibitor 2 (CDKN2) gene, a key cell cycle regulator with aberrant expression in HCC. However, its specific involvement remains unclear. Herein, we assessed the potential of CDKN2 expression as a promising biomarker for HCC progression, particularly for exhausted T cells. Our transcriptome analysis of CDKN2 in HCC revealed its significant role involving in HCC development. Remarkably, single-cell transcriptomic analysis revealed a notable correlation between CDKN2 expression, particularly CDKN2A, and Tex markers, which was further validated by a human cohort study using human HCC tissue microarray, highlighting CDKN2 expression as a potential biomarker for Tex within the intricate landscape of HCC progression. These findings provide novel perspectives that hold promise for addressing the unmet therapeutic need within HCC treatment.
Musa, Dickson A.;Aremu, Kolawole H.;Ajayi, Abraham;Smith, Stella I.
Microbiology and Biotechnology Letters
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v.48
no.2
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pp.230-235
/
2020
The global evolution of antibiotic resistance has threatened the efficacy of available treatment options with ravaging impacts observed in developing countries. As a result, investigations into the prevalence of antibiotic resistance and the role of plasmids are crucial. In this study, we investigated the presence and distribution of blaTEM and gyrA genes, plasmid profiles, and the antimicrobial susceptibility pattern of Salmonella strains isolated from raw meat and stool sources across Niger State, Nigeria. Ninety-eight samples, comprising 72 raw meat and 26 stool samples, were screened for Salmonella spp. The antimicrobial susceptibility of Salmonella isolates to 10 commonly used antimicrobial agents was determined using the KirbyBauer disc diffusion method. Isolates were further analyzed for plasmids, in addition to PCR amplification of beta-lactamase (blaTEM) and gyrA genes. A total of 31 Salmonella spp. were isolated, with 22 from raw meat (70.97%) and 9 from stool (29.03%). Salmonella spp. with multiple resistance patterns to ceftazidime, cefuroxime, ceftriaxone, erythromycin, ampicillin, cloxacillin, and gentamicin were detected. Ofloxacin and ciprofloxacin were found to be the most effective among the antibiotics tested, with 67.7% and 93.5% susceptible isolates, respectively. Nine (29.03%) isolates harbored plasmids with molecular sizes ranging between 6557 bp and 23137 bp. PCR amplification of gyrA was detected in 1 (3.23%) of the 31 isolates while 28 isolates (90.32%) were positive for blaTEM. This study shows the incidence of antibiotic resistance in Salmonella isolates and the possible role of plasmids; it also highlights the prevalence of ampicillin resistance in this local population.
The chances of disease pattern increased the importance of Health-promoting Lifestyle and a large part of the Health-promoting Lifestyle is associated with individual's habit. Health-promoting Lifestyle among nurses is very important because nurses could be a role model of patients and possibly influence many patients. The purpose of this study was oat on1y to assess how hospital nurses practice their Health-promoting Lifestyle but also to identify those affecting determinants. The subjects were 392 nurses working at 3 different hospital in Seoul. These data were collected by self administered questionnaire from April 27 to May 20, 2000. This study examined Health-promoting Lifestyle using In Sook Park's model, individual characteristics. Behavior-specific Cognitions and Affect factors using Pender's model and tried to fine out their relationships. The instruments used in this study were Health-promoting Lifestyle Profile developed by In Sock Park(1995). Likert's four-point scale was used also in this research. The percentage, mean standard deviation, AVNOVA, Pearson's correlation coefficient and multiple regression in the SAS package were used to analyze the data. The results of this study were as follows; 1. 52.3% of sample were aged between 25 and 29, 67.1% were single, 55.6% were university graduates, 51.8% earned 1.5 to 2.0 million won, 57.9% slept for d to 8 hours, 74.5% stated they were healthy. 2. 32.7% of sample worked in surgical gird department, 82.4% worked in 3 shift, 26.3% have been working as nurses for 5 to 7 years. Average score of Perceived self-efficacy was 3.63, Perceived benefits of action was 3.25, Social support was 2.75, and Perceived barriers to action was 1.87 which was the lowest score. 3. The average score if the performance in Health-promoting Lifestyle variable was 2.45 which was lower than previous study. The sanitary life Was 3.18 which was the highest score, harmonious relationship 3.13, emotional support 2.90. The variable with the highest degree of performance was the sanitary life, whereas the one with the west degree was the health diet. 4. There were no significant difference in perceived benefits of action with individual's a character, but in Perceived bait his of action there were significant differences with age(p<.01), marital status(p<.05), housing(p<.05), and Perceived health status(p<.05). In Perceived self-efficacy, there were significant differences with educational level(p<05), sleeping hours(p<.05), and BMI(p<.05). In Social support here were significant difference with housing and sleeping hours.
Kim, Dong-Chan;Kim, Seonlin;Hwang, Kyu-Seok;Kim, Cheol-Hee
Biomedical Science Letters
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v.23
no.1
/
pp.8-16
/
2017
p-Coumaric acid is an organic compound that is a hydroxyl derivative of cinnamic acid. Due to its multiple biological activities p-coumaric acid has been widely studied in biochemical and cellular systems and is also considered as a useful therapeutic candidate for various neuronal diseases. However, the efficacy of p-coumaric acid on zebrafish developmental regulation has not been fully explored. In this study, therefore, we first investigated the action mechanism of the p-coumaric acid on the zebrafish development in a whole-organism model. p-Coumaric acid treated group significantly inhibited the pigmentation of the developing zebrafish embryos compared with control embryos without any severe side effects. In addition, p-coumaric acid down-regulated more effectively in a lower concentration than the well-known zebrafish's melanogenic inhibitor, phenylthiourea. We also compared the molecular docking property of p-coumaric acid with phenylthiourea on the tyrosinase's kojic acid binding site, which is the key enzyme of zebrafish embryo pigmentation. Interestingly, p-coumaric acid interacted with higher numbers of the amino acid residues and exhibited a tight binding affinity to the enzyme than phenylthiourea. Taken all together, these results strongly suggest that p-coumaric acid inhibits the activity of tyrosinase, consequently down-regulating zebrafish embryo pigmentation, and might play an important role in the reduction of dermal pigmentation. Thus, p-coumaric acid can be an effective and non-toxic ingredient for anti-melanogenesis functional materials.
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