Roles of zinc-fingers and homeoboxes 1 during the proliferation, migration, and invasion of glioblastoma cells

Kwon, Ryuk-Jun,Han, Myoung-Eun,Kim, Youn-Jae,Kim, Yun Hak,Kim, Ji-young,Liu, Liangwen,Heo, Woong,Oh, Sae-Ock SAGE Publications 2017 TUMOR BIOLOGY Vol.39 No.3

<P>Zinc-fingers and homeoboxes 1 (ZHX1) is a nuclear transcription repressor and known to be involved in cell differentiation and tumorigenesis. However, the pathophysiological roles of ZHX1 have not been characterized in glioblastoma. We examined ZHX1 expression in glioblastoma patients' tissues and analyzed overall survival of the patients based on expression level of ZHX1. We also examined the effects of ZHX1 on proliferation and motility of glioblastoma cells. In silico analysis and immunohistochemical studies showed that the messenger RNA and protein expressions of ZHX1 were higher in the tissues of glioblastoma patients than in normal brain tissues, and that its overexpression was associated with reduced survival. In vitro, the downregulation of ZHX1 decreased the proliferation, migration, and invasion of glioblastoma cells, whereas its upregulation had the opposite effects. In addition, we showed ZHX1 could contribute to glioblastoma progression via the regulations of TWIST1 and SNAI2. Taken together, this study demonstrates that ZHX1 plays crucial roles in the progression of glioblastoma, and its findings suggest that ZHX1 be viewed as a potential prognostic maker and therapeutic target of glioblastoma.</P>

Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection

Jong Pil Ryuk,Gyu-Seog Choi,Jun Seok Park,Hye Jin Kim,Soo Yeun Park,Ghil Suk Yoon,Soo Han Jun,Yong Chul Kwon 대한외과학회 2014 Annals of Surgical Treatment and Research(ASRT) Vol.86 No.3

Purpose: Because predicting recurrence intervals and patterns would allow for appropriate therapeutic strategies, we evaluated the clinical and pathological characteristics of early and late recurrences of colorectal cancer. Methods: Patients who developed recurrence after undergoing curative resection for colorectal cancer stage I?III between January 2000 and May 2006 were identified. Early recurrence was defined as recurrence within 2 years after primary surgery of colorectal cancer. Analyses were performed to compare the clinicopathological characteristics and overall survival rate between the early and late recurrence groups. Results: One hundred fifty-eight patients experienced early recurrence and 64 had late recurrence. Multivariate analysis revealed that the postoperative elevation of carbohydrate antigen 19-9 (CA 19-9), venous invasion, and N stage correlated with the recurrence interval. The liver was the most common site of early recurrence (40.5%), whereas late recurrence was more common locally (28.1%), or in the lung (32.8%). The 5-year overall survival rates for early and late recurrence were significantly different (34.7% vs. 78.8%; P < 0.001). Survival rates after the surgical resection of recurrent lesions were not different between the two groups. Conclusion: Early recurrence within 2 years after surgery was associated with poor survival outcomes after colorectal cancer recurrence. An elevated postoperative CA 19-9 level, venous invasion, and advanced N stage were found to be significant risk factors for early recurrence of colorectal cancer.

STAT3 promotes motor neuron differentiation by collaborating with motor neuron-specific LIM complex

Lee, Seunghee,Shen, Rongkun,Cho, Hyong-Ho,Kwon, Ryuk-Jun,Seo, So Yeon,Lee, Jae W.,Lee, Soo-Kyung National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.28

<P>The motor neuron (MN)–hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN–hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN–hexamer–bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN–hexamer, enhancing the transcriptional activity of the MN–hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN–hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord.</P>

Isl1 Directly Controls a Cholinergic Neuronal Identity in the Developing Forebrain and Spinal Cord by Forming Cell Type-Specific Complexes

Cho, Hyong-Ho,Cargnin, Francesca,Kim, Yujin,Lee, Bora,Kwon, Ryuk-Jun,Nam, Heejin,Shen, Rongkun,Barnes, Anthony P.,Lee, Jae W.,Lee, Seunghee,Lee, Soo-Kyung Public Library of Science 2014 PLoS genetics Vol.10 No.4

<▼1><P>The establishment of correct neurotransmitter characteristics is an essential step of neuronal fate specification in CNS development. However, very little is known about how a battery of genes involved in the determination of a specific type of chemical-driven neurotransmission is coordinately regulated during vertebrate development. Here, we investigated the gene regulatory networks that specify the cholinergic neuronal fates in the spinal cord and forebrain, specifically, spinal motor neurons (MNs) and forebrain cholinergic neurons (FCNs). Conditional inactivation of <I>Isl1</I>, a LIM homeodomain factor expressed in both differentiating MNs and FCNs, led to a drastic loss of cholinergic neurons in the developing spinal cord and forebrain. We found that Isl1 forms two related, but distinct types of complexes, the Isl1-Lhx3-hexamer in MNs and the Isl1-Lhx8-hexamer in FCNs. Interestingly, our genome-wide ChIP-seq analysis revealed that the Isl1-Lhx3-hexamer binds to a suite of cholinergic pathway genes encoding the core constituents of the cholinergic neurotransmission system, such as acetylcholine synthesizing enzymes and transporters. Consistently, the Isl1-Lhx3-hexamer directly coordinated upregulation of cholinergic pathways genes in embryonic spinal cord. Similarly, in the developing forebrain, the Isl1-Lhx8-hexamer was recruited to the cholinergic gene battery and promoted cholinergic gene expression. Furthermore, the expression of the Isl1-Lhx8-complex enabled the acquisition of cholinergic fate in embryonic stem cell-derived neurons. Together, our studies show a shared molecular mechanism that determines the cholinergic neuronal fate in the spinal cord and forebrain, and uncover an important gene regulatory mechanism that directs a specific neurotransmitter identity in vertebrate CNS development.</P></▼1><▼2><P><B>Author Summary</B></P><P>Neurons utilize various chemicals to transmit signals to a target cell. Distinct types of neurons in the spinal cord and forebrain, collectively termed cholinergic neurons, utilize the same chemical, acetylcholine, for signal transmission. These neurons play critical roles in controlling locomotion and cognition. In this study, we have found that the <I>Isl1</I> gene orchestrates the process to generate cholinergic neurons in the spinal cord and forebrain. Isl1 forms two different types of multi-protein complexes in the spinal cord and forebrain. Both complexes bind the same genomic regions in a group of genes critical for cholinergic signal transmission, and promote their simultaneous expression. These cholinergic genes include enzymes that synthesize acetylcholine and proteins required to package acetylcholine into vesicles. The Isl1-containing multi-protein complexes were able to trigger the generation of cholinergic neurons in embryonic stem cells and neural stem cells. Our study reveals crucial mechanisms to coordinate the expression of genes in the same biological pathway in different cell types. Furthermore, it suggests a new strategy to produce cholinergic neurons from stem cells.</P></▼2>

Glucocorticoids Impair the 7α-Hydroxycholesterol-Enhanced Innate Immune Response

Son Yonghae,Kim Bo-Young,Kim Miran,Kim Jaesung,Kwon Ryuk Jun,김관회 대한면역학회 2023 Immune Network Vol.23 No.5

Glucocorticoids suppress the vascular inflammation that occurs under hypercholesterolemia, as demonstrated in an animal model fed a high-cholesterol diet. However, the molecular mechanisms underlying these beneficial effects remain poorly understood. Because cholesterol is oxidized to form cholesterol oxides (oxysterols) that are capable of inducing inflammation, we investigated whether glucocorticoids affect the immune responses evoked by 7α-hydroxycholesterol (7αOHChol). The treatment of human THP-1 monocytic cells with dexamethasone (Dex) and prednisolone (Pdn) downregulated the expression of pattern recognition receptors (PRRs), such as TLR6 and CD14, and diminished 7αOHChol-enhanced response to FSL-1, a TLR2/6 ligand, and lipopolysaccharide, which interacts with CD14 to initiate immune responses, as determined by the reduced secretion of IL-23 and CCL2, respectively. Glucocorticoids weakened the 7αOHChol-induced production of CCL2 and CCR5 ligands, which was accompanied by decreased migration of monocytic cells and CCR5-expressing Jurkat T cells. Treatment with Dex or Pdn also reduced the phosphorylation of the Akt-1 Src, ERK1/2, and p65 subunits. These results indicate that both Dex and Pdn impair the expression of PRRs and their downstream products, chemokine production, and phosphorylation of signaling molecules. Collectively, glucocorticoids suppress the innate immune response and activation of monocytic cells to an inflammatory phenotype enhanced or induced by 7αOHChol, which may contribute to the anti-inflammatory effects in hypercholesterolemic conditions.

Association between Sleep Duration and Presbycusis in Korean Adults: Korea National Health and Nutrition Examination Survey

Min Ju Kang,Youngin Lee,Yun Jin Kim,Sang Yeoup Lee,Jeong Gyu Lee,Yu Hyeon Yi,Young Hye Cho,Young Jin Tak,Eun Ju Park,Seung Hun Lee,Gyu Lee Kim,Jung In Choi,Young Jin Ra,Sae Rom Lee,Ryuk Jun Kwon,Soo M 대한가정의학회 2023 Korean Journal of Family Medicine Vol.44 No.2

Background: Sleep duration is associated with hearing loss, especially presbycusis, which is the most common type of hearing loss; however, there is limited evidence regarding this association among the Korean population. We aimed to determine the relationship between sleep duration and high-frequency hearing loss in Korean adults aged ≥40 years.Methods: We examined 5,547 Korean adults aged ≥40 years who completed audiometric tests and questionnaires regarding sleep duration during the 2010–2012 cycle of the Korea National Health and Nutrition Examination Sur-vey. Mild presbycusis was defined as >25 decibels (dB) and <40 dB, whereas moderate-to-severe presbycusis was defined as >40 dB pure tone averages at high frequencies (3,000, 4,000, and 6,000 Hz) for both ears. Additionally, the sleep duration was divided into quartiles. Odds ratios and 95% confidence intervals were estimated using mul-tivariable logistic regression after adjusting for covariates.Results: The prevalence of presbycusis in South Korean adults was 62.1%, of which 61.4% showed moderate to se-vere presbycusis. The incidence of moderate-to-severe, but not mild, presbycusis showed a significant positive cor-relation with sleep duration.Conclusion: Our findings suggest that sleep duration is associated with the prevalence of presbycusis.

Utilization of End-of-Life Care Rooms by Patients Who Died in a Single Hospice Unit at a National University Hospital in South Korea

Gyu Lee Kim,Seung Hun Lee,Yun Jin Kim,Jeong Gyu Lee,Yu Hyeon Yi,Young Jin Tak,Young Jin Ra,Sang Yeoup Lee,Young Hye Cho,Eun Ju Park,Young In Lee,Jung In Choi,Sae Rom Lee,Ryuk Jun Kwon,Soo Min Son Korean Society for Hospice and Palliative Care 2023 한국호스피스.완화의료학회지 Vol.26 No.2

Purpose: For the dignity of patients nearing the end of their lives, it is essential to provide end-of-life (EoL) care in a separate, dedicated space. This study investigated the utilization of specialized rooms for dying patients within a hospice unit. Methods: This retrospective study examined patients who died in a single hospice unit between January 1, 2017, and December 31, 2021. Utilizing medical records, we analyzed the circumstances surrounding death, the employment of specialized rooms for terminally ill patients, and the characteristics of those who received EoL care in a shared room. Results: During the 1,825-day survey period, deaths occurred on 632 days, and 799 patients died. Of these patients, 496 (62.1%) received EoL care in a dedicated room. The average duration of using this dedicated space was 1.08 days. Meanwhile, 188 patients (23.5%) died in a shared room. Logistic regression analysis revealed that a longer stay in the hospice unit was associated with a lower risk of receiving EoL care in a shared room (odds ratio [OR]=0.98, 95% confidence interval [CI] 0.97~0.99; P=0.002). Furthermore, a higher number of deaths on the day a patient died was associated with a greater risk of receiving EoL care in a shared room (OR=1.66, 95% CI 1.33~2.08; P<0.001). Conclusion: To ensure that more patients receive EoL care for an adequate duration in a private setting, additional research is necessary to increase the number of dedicated rooms and incorporate them into the hospice unit at an early stage.