Enteropathy and intestinal malabsorption in patients treated with antihypertensive drugs. A retrospective cohort study.

OBJECTIVES: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea. METHODS: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021. RESULTS: Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], p=0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], p=0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; p=0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; p=0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities. CONCLUSION: In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs.

Relationship between Pulse Pressure and Handgrip Strength in the Korean Population: A Nationwide Cross-Sectional Study.

Background: Sarcopenia is defined as the loss of muscle mass and strength and low physical performance, and it is closely related to the risk of cardiovascular disease and mortality. Pulse pressure (PP) is a biomarker of arterial stiffness and compliance. Elevated PP levels increase the risk of cardiovascular diseases and all-cause mortality. Nevertheless, the association between PP and sarcopenia has not yet been clearly established. Methods: Participant data were extracted from the Korea National Health and Nutrition Examination Survey conducted from 2014 to 2020. The study population was classified into three groups (PP < 40 mmHg, 40 mmHg ≤ PP < 60 mmHg, and PP ≥ 60 mmHg). PP was calculated by deducting the diastolic blood pressure from the systolic blood pressure. For handgrip strength, the maximum value measured with a grip dynamometer was adopted (weak handgrip strength: <28 kg for men, <18 kg for woman; normal handgrip strength: ≥28 kg for men, ≥18 kg for women). To determine the relationship between PP and the prevalence of weak handgrip strength, multiple logistic regression analysis was performed after adjusting for possible confounding factors. Results: The higher PP group had a higher age, body mass index; systolic blood pressure, prevalence of hypertension, diabetes, hyperlipidemia, and metabolic syndrome, and maximum handgrip strength. In all models, the prevalence of weak handgrip strength was significantly higher in the group with PP ≥ 60 mmHg compared to the control group (PP < 40 mmHg). Conclusions: Elevated PP was significantly associated with a higher prevalence of weak muscle strength. Thus, PP monitoring may be used to identify individuals at risk of sarcopenia and is helpful in improving health outcomes.

The association between reproductive period and handgrip strength in postmenopausal women: a nationwide cross-sectional study.

OBJECTIVE: Menarche and menopause are associated with muscle loss and strength in women. Handgrip strength (HGS) is a reliable measurement method of muscle strength. However, it is unclear whether the entire reproductive period, which encompasses both menarche and menopause, is associated with HGS in postmenopausal women. METHODS: A total of 2,354 postmenopausal women aged 45-75 years were included for statistical analysis. The reproductive period was divided into tertiles, and HGS was divided into four quartiles. HGS was measured to evaluate muscle strength. Binary logistic regression analysis was used to identify significant predictors with the first quartile HGS, derived from quartile data. Multiple logistic regression analysis was used to assess the relationship between the reproductive period (exposure) and low HGS (outcome). RESULTS: We found that the more extended the reproductive period, the lower the risk of low absolute HGS. This trend persisted even after controlling for other variables. Specifically, the odds ratio for low absolute HGS was 0.752 (95% confidence interval [CI], 0.563-1.000) for the second tertile reproductive period and 0.683 (95% CI, 0.513-0.900) for the third tertile reproductive period, with the first tertile reproductive period as the reference. The odds ratio for low relative HGS was 0.761 (95% CI, 0.551-1.052) for the second tertile reproductive period and 0.732 (95% CI, 0.533-0.972) for the third tertile reproductive period, using first tertile reproductive period as the reference, after covariate adjustment. CONCLUSIONS: A longer reproductive period is associated with a decreased risk of low HGS in postmenopausal women.

Effect of Combination Therapy with Ezetimibe and Statins versus Statin Monotherapy on Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis and a predictor of cardiovascular and cerebral events. The effects of ezetimibe on CIMT have been inconsistently reported. The aim of this meta-analysis is to compare the effects of ezetimibe/statin and statin alone therapies on CIMT reduction. Materials and Methods: The PubMed, Embase, and Cochrane library databases were searched for randomized controlled trials (RCTs) published prior to 26 January 2023 with the MeSH keywords 'Ezetimibe' and 'Carotid Intima-Media Thickness'. The results were presented as standard mean difference (SMD) with 95% confidence intervals using the random-effect model method, and heterogeneity was assessed. Subgroup, meta-regression, and sensitivity analyses were conducted. Results: Five RCTs with 642 participants were included. CIMT reduction was not significantly different between the ezetimibe/statin and statin alone groups. However, in subgroup analyses, CIMT in the ezetimibe/statin group was significantly reduced in patients with non-familial hypercholesterolemia (SMD: -0.34 mm and p = 0.002) and in patients with secondary prevention (SMD: -0.38 mm and p = 0.002). The low-density lipoprotein cholesterol level was significantly reduced in the ezetimibe/statin group (SMD: -0.58 mg/dL and p < 0.001). Conclusions: The effect of ezetimibe on CIMT reduction was shown in non-familial hypercholesterolemia and secondary prevention. These results suggest that the efficacy of ezetimibe may vary with potential CIMT reduction benefits in certain subpopulations.

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

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.

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

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.

Prevalence and clinical characteristics of low skeletal muscle index among adults visiting a health promotion center: Cross-sectional study.

Sarcopenia causes a variety of functional impairments and is associated with all-cause mortality, but once it occurs, it is difficult to treat and reverse. However, the prevalence of sarcopenia in healthy people has never been investigated due to the low awareness of sarcopenia in healthy people. This cross-sectional study was conducted in a single health promotion center from the January 1st 2020 to the December 31st 2021. Adults aged 18 years and older with an Inbody as part of their health checkup were included, and all data was collected from the EMR. Obesity was defined as a body mass index (BMI) of 23 (kg/m2) or more by Korean standards, and low skeletal muscle mass was defined as a skeletal muscle index (SMI) of <0.789 for men and <0.512 for women. 60.5% of the total participants (n = 5993) had low skeletal muscle mass. The low SMI group had lower BMI, waist circumference, and abdominal skinfold than the normal SMI group (low SMI group vs normal SMI: BMI; 25.47 ±â€…2.96 vs 22.98 ±â€…3.05, P < .001, waist circumference; 90.31 ±â€…8.80 cm vs 82.69 ±â€…9.71 cm, P < .001, abdominal skinfold; 18.78 ±â€…2.44 mm vs 15.99 ±â€…2.12 mm, P < .001). The body fat percentage was higher in the low SMI group than in the normal SMI group 25.30 ±â€…6.23% versus 29.82 ±â€…7.07%, P < .001. Triglyceride and uric acid levels were low in the low SMI group (TG; 147.69 ±â€…97.27 vs 115.86 ±â€…68.31, P < .001, uric acid level; 6.30 ±â€…1.38 vs 5.23 ±â€…1.30, P < .001) and high-density lipid (HDL) was high (HDL; 53.17 ±â€…11.41 vs 59.89 ±â€…14.72, P < .001). The odds ratio of low SMI prevalence for age, sex, BMI, fat body percent, and triglycerides relative to normal SMI was 1.05 (P = .031), 0.14 (P < .001), 0.12 (P < .001), 2.05 (P < .001), and 0.99 (P = .003), respectively. Of those who visited the Health Promotion Center, more than 60% had low SMI identified through Inbody. Low BMI and high body fat percentage increase the risk of low SMI. Compared to normal and low SMI based on obesity, Sex, height, BW, abdominal skinfold, and waist circumflex showed significant P values in both groups. The factors related to low SMI were TG, HDL, and uric acid levels.

Association between weekend catch-up sleep and hyperuricemia with insufficient sleep in postmenopausal Korean women: a nationwide cross-sectional study.

OBJECTIVE: Hyperuricemia is associated with metabolic and cardiovascular diseases and mortality. Efforts to lower the risk of hyperuricemia in various ways are needed as the prevalence of these diseases increases in postmenopausal women. Studies have shown that one of these methods is associated with adequate sleep duration, which is related to a low risk of hyperuricemia. Considering that it is difficult for people to get enough sleep in modern society, this study hypothesized that weekend catch-up sleep could be an alternative. To our knowledge, no past study has investigated the relation between weekend catch-up sleep and hyperuricemia in postmenopausal women. Hence, the aim of this research was to estimate the relation between weekend catch-up sleep and hyperuricemia with insufficient sleep in postmenopausal women during weekday or workday. METHODS: This study included 1,877 participants extracted from the Korea National Health and Nutrition Examination Survey VII. The study population was divided into weekend catch-up sleep and non-weekend catch-up sleep groups. Odds ratios with 95% confidence intervals were derived using multiple logistic regression analysis. RESULTS: Weekend catch-up sleep had a significantly lower prevalence of hyperuricemia after adjusting for confounders (odds ratio, 0.758 [95% confidence interval, 0.576-0.997]). In a subgroup analysis, weekend catch-up sleep of 1 to 2 hours was significantly correlated with a lower prevalence of hyperuricemia after adjusting for confounders (odds ratio: 0.522 [95% confidence interval, 0.323-0.845]). CONCLUSIONS: Weekend catch-up sleep had a decreased prevalence of hyperuricemia in postmenopausal women with sleep deprivation.

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

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 Survey. 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 multivariable 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 severe presbycusis. The incidence of moderate-to-severe, but not mild, presbycusis showed a significant positive correlation with sleep duration. CONCLUSION: Our findings suggest that sleep duration is associated with the prevalence of presbycusis.

Multiarray Biosensor for Diagnosing Lung Cancer Based on Gap Plasmonic Color Films.

Adaptable and sensitive materials are essential for the development of advanced sensor systems such as bio and chemical sensors. Biomaterials can be used to develop multifunctional biosensor applications using genetic engineering. In particular, a plasmonic sensor system using a coupled film nanostructure with tunable gap sizes is a potential candidate in optical sensors because of its simple fabrication, stability, extensive tuning range, and sensitivity to small changes. Although this system has shown a good ability to eliminate humidity as an interferant, its performance in real-world environments is limited by low selectivity. To overcome these issues, we demonstrated the rapid response of gap plasmonic color sensors by utilizing metal nanostructures combined with genetically engineered M13 bacteriophages to detect volatile organic compounds (VOCs) and diagnose lung cancer from breath samples. The M13 bacteriophage was chosen as a recognition element because the structural protein capsid can readily be modified to target the desired analyte. Consequently, the VOCs from various functional groups were distinguished by using a multiarray biosensor based on a gap plasmonic color film observed by hierarchical cluster analysis. Furthermore, the lung cancer breath samples collected from 70 healthy participants and 50 lung cancer patients were successfully classified with a high rate of over 89% through supporting machine learning analysis.

Association between pulse pressure and low muscle mass in Korean adults: A nationwide cross-sectional study.

Sarcopenia is characterized by a loss of muscle mass and strength and is associated with a high risk of cardiovascular events and increased mortality. Pulse pressure (PP) serves as a marker for changes in heart structure and function, as well as arterial stiffness. A high PP also increases the risk of cardiovascular disease and all-cause mortality. However, the relationship between PP and sarcopenia is poorly understood. We used the data of participants of the Korea National Health and Nutrition Examination Survey (KNHANES) of 2008 to 2011. Participants were divided into a control group (PP < 40 mm Hg) and a high-PP group (PP ≥ 40 mm Hg). PP was calculated by subtracting the diastolic blood pressure (DBP) from the systolic blood pressure (SBP), and the low muscle index was assessed using appendicular skeletal muscle mass (ASM) normalized by body mass index (BMI). Multiple logistic regression analyses were performed to examine the association between PP and the prevalence of low muscle mass, adjusting for potential confounders. The high-PP group had a higher age, SBP, DBP, and prevalence of hypertension, diabetes and hyperlipidemia than the control group. The high-PP group had a higher prevalence of low muscle mass than the control group in all models. A high PP is significantly associated with a higher prevalence of low muscle mass. Therefore, PP monitoring may help identify individuals at risk of sarcopenia and guide interventions to improve health outcomes.

MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.

BACKGROUND: The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. METHODS: We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. RESULTS: MHY4571 inhibited PKA activity (> 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. CONCLUSIONS: Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.

Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study.

BACKGROUND: Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown. METHODS: Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann-Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC. RESULTS: The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan-Meier and multivariate regression analyses. CONCLUSIONS: As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.

Prognosis palliative care study, palliative prognostic index, palliative prognostic score and objective prognostic score in advanced cancer: a prospective comparison.

BACKGROUND: Predicting how long a patient with far advanced cancer has to live is a significant part of hospice and palliative care. Various prognostic models have been developed, but have not been fully compared in South Korea. OBJECTIVES: We aimed to compare the accuracy of the Prognosis in Palliative Care Study (PiPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP) and Objective Prognostic Score (OPS) for patients with far advanced cancer in a palliative care unit in South Korea. METHODS: This prospective study included patients with far advanced cancer who were admitted to a single palliative care unit at the National University Hospital. Variables for calculating the prognostic models were recorded by a palliative care physician. The survival rate was estimated using the Kaplan-Meier method. The sensitivity, specificity, positive predictive value and negative predictive value of each model were calculated. RESULTS: A total of 160 patients participated. There was a significant difference in survival rates across all groups, each categorised through the five prognostic models. The overall accuracy (OA) of the prognostic models ranged between 54.5% and 77.6%. The OA of clinicians' predictions of survival ranged between 61.9% and 81.3%. CONCLUSION: The PiPS, PPI, PaP and OPS were successfully validated in a palliative care unit of South Korea. There was no difference in accuracy between the prognostic models, and OA tended to be lower than in previous studies.

Association Between Weekend Catch-Up Sleep and Metabolic Syndrome with Sleep Restriction in Korean Adults: A Cross-Sectional Study Using KNHANES.

BACKGROUND: Many researchers have identified that adequate sleep duration is linked to the quality of life and metabolic diseases. Nowadays, it is hard to take enough sleep, so weekend catch-up sleep (CUS) may be an alternative option in modern society. To our knowledge, no previous studies reported the association between weekend CUS and metabolic syndrome, especially in the Korean population. OBJECTIVE: We investigated the association between weekend CUS and the prevalence of metabolic syndrome in Korean adults (≥20 years old) with less than 6 hours of average weekday sleep. PATIENTS AND METHODS: A total of 1,453 individuals were selected from the Korean National Health and Nutrition Examination Survey. Weekend CUS was divided into four categories: ≤0 hour, 0-1 hour, 1-2 hours, and ≥2 hours. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived by univariate and multivariate logistic regression analyses. RESULTS: Participants with weekend CUS ≥1 hour had decreased risk of metabolic syndrome in univariate analysis (CUS 1-2 hours: OR: 0.413, 95% CI: 0.301-0.568; CUS ≥2 hours: OR: 0.382, 95% CI 0.296-0.493). Weekend CUS 1-2 hours reduced the risk of metabolic syndrome in multivariate logistic regression analysis (OR: 0.552, 95% CI: 0.369-0.823). Based on the age group analysis, weekend CUS ≥1 hour reduced the metabolic syndrome among those aged 20-39 and 40-65 (20-39: CUS 1-2 hours OR: 0.248, 95% CI: 0.078-0.783, CUS ≥2 hours OR: 0.374, 95% CI: 0.141-0.991; 40-65: CUS 1-2 hours OR: 0.507, 95% CI 0.309-0.832 CUS ≥2 hours OR: 0.638, 95% CI: 0.415-0.981). CONCLUSION: Weekend CUS was associated with a low risk of metabolic syndrome among Korean adults with sleep restriction.

Receptor-interacting protein kinase 3 as a predictive adjuvant chemotherapy marker after lung adenocarcinoma resection.

BACKGROUND: This study assessed the predictive value of receptor-interacting protein kinase 3 (RIPK3) expression and its correlation with clinicopathological characteristics, disease-free survival, and overall survival of patients with cisplatin-based adjuvant chemotherapy after lung adenocarcinoma resection. METHODS: This study included 50 patients who underwent cisplatin-based adjuvant chemotherapy after lung adenocarcinoma (stage IB-IIIA) resection. Immunohistochemical analysis was performed by probing tumor tissue microarrays with anti-RIPK3 antibody. RESULTS: High RIPK3 expression was detected in 24 (48.0%) of the 50 patients. Moreover, high RIPK3 expression was associated with a prolonged disease-free survival (P=0.015) but not with a prolonged overall survival (P=0.109) of the patients who underwent cisplatin doublet therapy after lung adenocarcinoma resection. We also examined whether RIPK3 expression was associated with prognosis based on chemotherapeutic response and found that patients with low RIPK3 expression showed a higher tendency of developing a progressive disease [14/26 (53.8%) patients] than patients with high RIPK3 expression [6/24 (25.0%) patients] (P=0.03). Results of Cox univariate proportional hazards regression model showed that age, N stage, and high RIPK3 expression (P=0.04) were associated with the prolonged disease-free survival of the patients who underwent cisplatin-based adjuvant chemotherapy after lung adenocarcinoma resection. CONCLUSIONS: These results suggest that RIPK3 overexpression is a potential biomarker to identify patients with lung adenocarcinoma who can benefit the most from cisplatin-based adjuvant chemotherapy after complete adenocarcinoma resection.

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

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.

Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma.

Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage. Furthermore, Kaplan-Meier and multivariate regression analysis showed that reduction in the mRNA expression of ZHX1 was associated with poorer survival. Taken together, the present study shows loss of ZHX1 is correlated with ccRCC progression and suggests it is an independent prognostic marker in ccRCC.

ZHX1 Promotes the Proliferation, Migration and Invasion of Cholangiocarcinoma Cells.

Zinc-fingers and homeoboxes 1 (ZHX1) is a transcription repressor that has been associated with the progressions of hepatocellular carcinoma, gastric cancer, and breast cancer. However, the functional roles of ZHX1 in cholangiocarcinoma (CCA) have not been determined. We investigated the expression and roles of ZHX1 during the proliferation, migration, and invasion of CCA cells. In silico analysis and immunohistochemical studies showed amplification and overexpression of ZHX1 in CCA tissues. Furthermore, ZHX1 knockdown using specific siRNAs decreased CCA cell proliferation, migration, and invasion, whereas ZHX1 overexpression promoted all three characteristics. In addition, results suggested EGR1 might partially mediate the effect of ZHX1 on the proliferation of CCA cells. Taken together, these results show ZHX1 promotes CCA cell proliferation, migration, and invasion, and present ZHX1 as a potential target for the treatment of CCA.

Isl1 directly controls a cholinergic neuronal identity in the developing forebrain and spinal cord by forming cell type-specific complexes.

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 Isl1, 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.