Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis

Background@#The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/ Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). @*Methods@#In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. @*Results@#The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. @*Conclusion@#CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance.The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

Restoration of Immune Privilege in Human Dermal Papillae Controlling Epithelial-Mesenchymal Interactions in Hair Formation

BACKGROUND@#Hair follicles are among a handful of organs that exhibit immune privilege. Dysfunction of the hair follicle immune system underlies the development of inflammatory diseases, such as alopecia areata. @*METHODS@#Quantitative reverse transcription PCR and immunostaining was used to confirm the expression of major histocompatibility complex class I in human dermal papilla cells. Through transcriptomic analyses of human keratinocyte stem cells, major histocompatibility complex class I was identified as differentially expressed genes. Organ culture and patch assay were performed to assess the ability of WNT3a conditioned media to rescue immune privilege. Lastly, CD8? T cells were detected near the hair bulb in alopecia areata patients through immunohistochemistry. @*RESULTS@#Inflammatory factors such as tumor necrosis factor alpha and interferon gamma were verified to induce the expression of major histocompatibility complex class I proteins in dermal papilla cells. Additionally, loss of immune privilege of hair follicles was rescued following treatment with conditioned media from outer root sheath cells. Transcriptomic analyses found 58 up-regulated genes and 183 down-regulated genes related in MHC class I? cells. Using newborn hair patch assay, we demonstrated that WNT3a conditioned media with epidermal growth factor can restore hair growth. In alopecia areata patients, CD8? T cells were increased during the transition from mid-anagen to late catagen. @*CONCLUSION@#Identification of mechanisms governing epithelial and mesenchymal interactions of the hair follicle facilitates an improved understanding of the regulation of hair follicle immune privilege.

Predictions of Sampling Site Based on Microbial Compositions Using a Decision Tree-based Method

The nose and throat are sites commonly used to obtain swab specimens to diagnose upper respiratory tract infections, and some studies have shown differences between the diagnostic accuracies of nose and throat swabs for upper respiratory infections. However, current sampling methods for the diagnosis of upper respiratory tract infections do not differentiate between nose and throat samples. The present study was undertaken to devise a means of determining whether samples were obtained from the nose or throat.Microbiome abundance data of 576 upper respiratory swab samples were obtained from the human microbiome project website. Predictive models were generated to determine sampling sites based on microbiomes using the random forest and regression tree with recursive partitioning methods. The final prediction model showed a near-perfect prediction for sampling sites using only the abundances of Staphylococcaceae and Streptococcaceae. The devised model can be used to predict sampling sites for upper respiratory specimens.

Predictions of Sampling Site Based on Microbial Compositions Using a Decision Tree-based Method

The nose and throat are sites commonly used to obtain swab specimens to diagnose upper respiratory tract infections, and some studies have shown differences between the diagnostic accuracies of nose and throat swabs for upper respiratory infections. However, current sampling methods for the diagnosis of upper respiratory tract infections do not differentiate between nose and throat samples. The present study was undertaken to devise a means of determining whether samples were obtained from the nose or throat.Microbiome abundance data of 576 upper respiratory swab samples were obtained from the human microbiome project website. Predictive models were generated to determine sampling sites based on microbiomes using the random forest and regression tree with recursive partitioning methods. The final prediction model showed a near-perfect prediction for sampling sites using only the abundances of Staphylococcaceae and Streptococcaceae. The devised model can be used to predict sampling sites for upper respiratory specimens.

Analysis of Intestinal Mucosal Microbiome Changes before and after Chemoradiation in Locally Advanced Rectal Cancer Patients

PURPOSE: Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.MATERIALS AND METHODS: We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.RESULTS: At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.CONCLUSION: This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.

Developing a new index to assess varicella outbreak / 영남의대학술지

BACKGROUND: Varicella is the most common infectious disease reported despite the high vaccination rate. Interventions that target humans are particularly effective for varicella because humans are its only natural host. On the other hand, the existing national varicella surveillance systems lack the information to identify an outbreak. Therefore, a new index to assess varicella outbreaks was developed.METHODS: The residential addresses of 2,718 varicella cases reported in Daegu in 2016 were converted to geographic coordinates and the distances between new varicella case and previous cases within 21 days were calculated from the date analyzed. Two cases were considered to be adjacent if the distance between them was less than 1 km. Finally, a proximity index was introduced by dividing the number of adjacent cases by the number of new cases on the date analyzed.RESULTS: First, time-series charts and scatter plots were used to verify that the proximity index reflected the spatial closeness of the different varicella cases. The proximity index is helpful in identifying outbreaks from a list of single varicella cases. In addition, in this study, a new epidemic characteristic of varicella based on the proximity index was shown.CONCLUSION: The proximity index introduced in this study can be used to determine the likelihood of an outbreak from a single case of varicella, and it can be embedded in a web-based national varicella surveillance system that is currently in operation.

Developing a new index to assess varicella outbreak / 영남의대학술지

BACKGROUND: Varicella is the most common infectious disease reported despite the high vaccination rate. Interventions that target humans are particularly effective for varicella because humans are its only natural host. On the other hand, the existing national varicella surveillance systems lack the information to identify an outbreak. Therefore, a new index to assess varicella outbreaks was developed. METHODS: The residential addresses of 2,718 varicella cases reported in Daegu in 2016 were converted to geographic coordinates and the distances between new varicella case and previous cases within 21 days were calculated from the date analyzed. Two cases were considered to be adjacent if the distance between them was less than 1 km. Finally, a proximity index was introduced by dividing the number of adjacent cases by the number of new cases on the date analyzed. RESULTS: First, time-series charts and scatter plots were used to verify that the proximity index reflected the spatial closeness of the different varicella cases. The proximity index is helpful in identifying outbreaks from a list of single varicella cases. In addition, in this study, a new epidemic characteristic of varicella based on the proximity index was shown. CONCLUSION: The proximity index introduced in this study can be used to determine the likelihood of an outbreak from a single case of varicella, and it can be embedded in a web-based national varicella surveillance system that is currently in operation.

Discovery of a New DNA Gyrase A Inhibitor, 4-(1-methyl-6-nitroquinolin-1-ium-4-yl)amino-N-4-(1-methylpyridin-1-ium-4-yl)aminophenylbenzamide

Escherichia coli (E. coli) is a clinically important causative organism that can lead to urinary tract infections. Quinolone antibiotics are among the first-line treatments for urinary tract infections. However, the frequency of resistance to quinolone in E. coli has been increasing. Therefore, new antimicrobial agents that can be used for treatment in lieu of quinolone antibiotics are needed. In this study, thirty-six compounds with higher scores in a virtual screening based on the three-dimensional structure of E. coli DNA gyrase were selected for in vitro antimicrobial activity testing. An in vitro test confirmed the antimicrobial activity of 4-[(1-methyl-6-nitroquinolin-1-ium-4-yl)amino]-N-[4-[(1-methylpyridin-1-ium-4-yl)amino]phenyl]benzamide (ZINC18057104) against E. coli among the 36 compounds. The minimum inhibitory concentration (MIC) of ZINC18057104 against E. coli ATCC® 25922™ was 2 μg/ml, and the MIC₅₀ and MIC₉₀ for the 72 quinolone-resistant E. coli clinical isolates were 4 and 64 μg/ml, respectively. ZINC18057104, which has a quinoline structure which is similar to the quinolone antibiotics, is predicted to exhibit antimicrobial activity in quinolone-resistant E. coli because it has different molecular interactions with the DNA gyrase than that of existing quinolone antibiotics.

Microbial Profile of the Stomach: Comparison between Normal Mucosa and Cancer Tissue in the Same Patient

Gastric cancer is the third most common cancer and the third most frequent cause of cancer mortality in Asia. It is predicted that gastric cancer will remain an important cause of death at least during the next half century because of the increasing number of new cases in an aging population. However, little has been revealed about the role of gastric microbes and their reaction to gastric cancer. In this study, we identified differences in the microbial communities between gastric cancer and normal gastric mucosa by comparing the microbiomes of tissues from the same patients. The clustering analysis results showed different bacterial communities between normal gastric mucosa and gastric cancer. A comparison of bacterial communities at the species level revealed that Helicobacter pylori was significantly reduced in cancer tissue compared to that in normal gastric mucosa in the same patient. A comparison at the genus level showed that Propionibacterium spp., Staphylococcus spp., and Corynebacterium spp. had significantly reduced populations in cancer tissue, whereas Clostridium spp. and Prevotella spp. had significantly increased populations in cancer tissue.

Sonication Induces Apoptosis in HL-60 Cells / 계명의대학술지

To investigate a specific mechanism of apoptosis induced by sonication, we applied 20 kHz ultrasound to leukemia cell line HL-60 with different intensities (0-60 W/cm2) and time durations (0-100 sec). In accordance with previous reports, ultrasound treatment in HL-60 cells induced immediate cell death and delayed cell death which are associated with cell lysis and apoptosis, respectively. Delayed cell death of HL-60 was also detected 5 hours after sonication in our experiment. Detection of caspase activation by Western blot and sub-G1 accumulation by flow cytometry confirmed that apoptosis plays a role in delayed cell death induced by sonication in HL-60 cells. In addition, we found that decrease in lysosomes of HL-60 cells after sonication suggesting lysosomal rupture is involved in the mechanism of cell death induced by sonication.

Genome-Wide Association Study of Medication Adherence in Chronic Diseases in the Korean Population

Medication adherence is generally defined as the extent of voluntary cooperation of a patient in taking medicine as prescribed. Adherence to long-term treatment with chronic disease is essential for reducing disease comorbidity and mortality. However, medication non-adherence in chronic disease averages 50%. This study was conducted a genome-wide association study to identify the genetic basis of medication adherence. A total of 235 medication non-adherents and 1,067 medication adherents with hypertension or diabetes were used from the Korean Association Resource project data according to the self-reported treatment status of each chronic disease, respectively. We identified four single nucleotide polymorphisms with suggestive genome-wide association. The most significant single nucleotide polymorphism was rs6978712 (chromosome 7, p = 4.87 x 10-7), which is located proximal to the GCC1 gene, which was previously implicated in decision-making capability in drug abusers. Two suggestive single nucleotide polymorphisms were in strong linkage disequilibrium (r2 > 0.8) with rs6978712. Thus, in the aspect of decision-making in adherence behavior, the association between medication adherence and three loci proximal to the GCC1 gene seems worthy of further research. However, to overcome a few limitations in this study, defining the standardized phenotype criteria for self-reported adherence should be performed before replicating association studies.