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Ginsenosides in ginseng are known for their potential health benefits, including antioxidant properties and their potential to exhibit anticancer effects. Besides a various range of coding genes, ginsenosides impose their efficacy by targeting noncoding RNAs. Long noncoding RNA (lncRNA) has gained significant attention from both basic and clinical oncology fields due to its involvement in various cancer cell activities such as proliferation, apoptosis, metastasis, and autophagy. These events can be achieved either by lncRNA alone or in association with microRNAs or proteins. This review aims to summarize the diverse activities of lncRNAs that are regulated by ginsenosides, focusing on their role in regulating target genes through signaling pathways in human diseases. We highlight the results of studies on the expression profiles of lncRNAs induced by ginsenosides in efforts to inhibit cancer cell proliferation. Finally, we discuss the potential and challenges of utilizing lncRNAs as diagnostic markers for disease treatment.

Objective To assess the safety and effectiveness of high-density light-emitting diode (LED) irradiation therapy in patients with hand osteoarthritis (OA) and compare the pre- and post-intervention symptoms. Methods Twenty-three patients with hand OA underwent eight sessions of high-density LED irradiation therapy directed at the five most painful areas in the finger joints. Each session lasted for 18 minutes; and the sessions were conducted twice a week, for 4 weeks. We evaluated the degree of pain using the visual analogue scale, ring size, and passive range of motion (flexion+extension) for two most painful joints from the baseline to post-therapy (weeks 4 and 6). Results High-density LED irradiation therapy significantly reduced the pain posttreatment compared with that observed at the baseline (p0.05). No adverse events were observed. Conclusion We examined the safety and effectiveness of high-density LED irradiation therapy in reducing pain and hand swelling and improving joint mobility in patients with hand OA. These results suggest that high-density LED irradiation therapy has the potential to be an important strategy for managing hand OA.

IntroductionIndividuals with gender dysphoria do not identify with their sex assigned at birth and face societal and cultural challenges, leading to increased risk for depression, anxiety, and suicide. Gender dysphoria is a DSM-5 diagnosis but is not necessary for transition therapy. Additionally, individuals with gender dysphoria or who identify as gender diverse/nonconforming may experience “minority stress” from increased discrimination, leading to a greater risk for mental health problems. This study aimed to identify possible health disparities in patients hospitalized for depression with gender dysphoria across the United States. Depression was selected because patients with gender dysphoria are at an increased risk for it. Various patient and hospital-related factors are explored for their association with changes in healthcare utilization for patients hospitalized with depression.MethodsThe National Inpatient Sample was used to identify nationwide patients with depression (n = 378,552, weighted n = 1,892,760) from 2016 to 2019. We then examined the characteristics of the study sample and investigated how individuals’ gender dysphoria was associated with healthcare utilization measured by hospital cost per stay. Multivariate survey regression models were used to identify predictors.ResultsAmong the 1,892,760 total depression inpatient samples, 14,145 (0.7%) patients had gender dysphoria (per ICD-10 codes). Over the study periods, depression inpatients with gender dysphoria increased, but total depression inpatient rates remained stable. Survey regression results suggested that gender dysphoria, minority ethnicity or race, female sex assigned at birth, older ages, and specific hospital regions were associated with higher hospital cost per stay than their reference groups. Sub-group analysis showed that the trend was similar in most racial and regional groups.ConclusionDifferences in hospital cost per stay for depression inpatients with gender dysphoria exemplify how this community has been disproportionally affected by racial and regional biases, insurance denials, and economic disadvantages. Financial concerns can stop individuals from accessing gender-affirming care and risk more significant mental health problems. Increased complexity and comorbidity are associated with hospital cost per stay and add to the cycle.

Objective To evaluate the efficacy of light-emitting diode (LED) and their dual-wavelengths as a treatment strategy for osteoarthritis. Methods We induced osteoarthritis in male Sprague-Dawley rats by intra-articular injection of sodium iodoacetate into the right rear knee joint. The animals with lesions were divided into an untreated group and an LED-treated group (n=7 each). In the LED-treated group, the lesioned knee was irradiated with lasers (850 and 940 nm) and dose (3.15 J/cm2) for 20 minutes per session, twice a week for 4 weeks. Knee joint tissues were stained and scanned using an in vivo micro-computed tomography (CT) scanner. Serum interleukin (IL)-6 and IL-18 levels were determined using enzyme-linked immuno-sorbent assay. Several functional tests (lines crossed, rotational movement, rearing, and latency to remain rotating rod) were performed 24 hours before LED treatment and at 7, 14, 21, and 28 days after treatment. Results LED-treated rats showed improved locomotor function and suppressed matrix-degrading cytokines. Micro-CT images indicated that LED therapy had a preserving effect on cartilage and cortical bone. Conclusion LED treatment using wavelengths of 850 and 940 nm resulted in significant functional, anatomical, and histologic improvements without adverse events in a rat model. Further research is required to determine the optimal wavelength, duration, and combination method, which will maximize treatment effectiveness.

Background Pneumonia is one of the leading causes of hospital admission in the United States with a global health burden of about 6.8 million hospitalizations and 1.1 million deaths in patients over 65 years old in 2015. This study aimed to identify possible patient and hospital-related risk factors for in-hospital pneumonia death across US hospitals.Methods The National Inpatient Sample (NIS) was used to identify nationwide pneumonia patients (n = 374 766, weighted n = 1 873 828) from 2016 to 2019. We examined the characteristics of the study sample and their association with in-hospital death. Multivariate survey logistic regression models were used to identify risk factors.Results During the study periods, in-hospital death rates continuously decreased (2.45% in 2016 to 2.19% in 2019). Descriptive statistics showed that patient and hospital factors had varied in-hospital death rates. Survey logistic regression results suggested that male, very low income, non-Medicare, government hospitals, rural hospitals, and specific hospital regions were associated with higher in-hospital death rates than their reference groups.Conclusion Socioeconomic factors, including income and insurance, are associated with pneumonia mortality. Census region, hospital ownership, and rural location are also related to in-hospital mortality. Such findings in underserved, impoverished, and rural areas to identify possible health disparities.

BackgroundCardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia–reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction. Purinergic signaling, as regulated by CD39 and CD73, has emerged as centrally important in the context of organ-specific IRI. Hence, comprehensive understanding of such purinergic responses may be likewise imperative for improving outcomes in PCAS.MethodsWe have investigated alterations of immune cell populations after CA by utilizing rodent models of PCAS. Blood and spleen were collected after CA and resuscitation and underwent flow cytometry analysis to evaluate shifts in CD3+CD4+ helper T cells, CD3+CD8a+ cytotoxic T cells, and CD4/CD8a ratios. We then examined the expression of CD39 and CD73 across diverse cell types, including myeloid cells, T lymphocytes, and B lymphocytes.ResultsIn both rat and mouse models, there were significant increases in the frequency of CD3+CD4+ T lymphocytes in PCAS (rat, P < 0.01; mouse, P < 0.001), with consequently elevated CD4/CD8a ratios in whole blood (both, P < 0.001). Moreover, CD39 and CD73 expression on blood leukocytes were markedly increased (rat, P < 0.05; mouse, P < 0.01 at 24h). Further analysis in the experimental mouse model revealed that CD11b+ myeloid cells, with significant increase in their population (P < 0.01), had high level of CD39 (88.80 ± 2.05 %) and increased expression of CD73 (P < 0.05). CD19+ B lymphocytes showed slight increases of CD39 (P < 0.05 at 2h) and CD73 (P < 0.05 at 2h), while, CD3+ T lymphocytes had decreased levels of them. These findings suggested a distinct patterns of expression of CD39 and CD73 in these specific immune cell populations after CA.ConclusionsThese data have provided comprehensive insights into the immune response after CA, highlighting high-level expressions of CD39 and CD73 in myeloid cells.

Abstract Background Lung cancer health disparities are related to various patient factors. This study describes regional differences in healthcare utilization and racial characteristics to identify high-risk areas. This study aimed to identify regions and races at greater risk for lung cancer health disparities based on differences in healthcare utilization, measured here by hospital charges and length of stay. Methods The National Inpatient Sample of the United States was used to identify patients with lung cancer (n = 92,159, weighted n = 460,795) from 2016 to 2019. We examined the characteristics of the patient sample and the association between the racial and regional variables and healthcare utilization, measured by hospital charges and length of stay. The multivariate sample weighted linear regression model estimated how racial and regional variables are associated with healthcare utilization. Results Out of 460,795 patients, 76.4% were white, and 40.2% were from the South. The number of lung cancer patients during the study periods was stable. However, hospital charges were somewhat increased, and the length of stay was decreased during the study period. Sample weighted linear regression results showed that Hispanic & Asian patients were associated with 21.1% and 12.3% higher hospital charges than White patients. Compared with the Northeast, Midwest and South were associated with lower hospital charges, however, the West was associated with higher hospital charges. Conclusion Minority groups and regions are at an increased risk for health inequalities because of differences in healthcare utilization. Further differences in utilization by insurance type may exacerbate the situation for some patients with lung cancer. Hospital managers and policymakers working with these patient populations in identified areas should strive to address these disparities through special prevention programs and targeted financial assistance.

Abstract Background Although strengthening coverage has improved cancer care, there are concerns related to medical distortion. Previous studies have only examined whether patients visit a specific hospital, and not the continuum of patients with cancer, resulting in a lack of evidence in South Korea. This study aimed to investigate the patterns in hospital type for cancer care and analyze their association with outcomes. Methods The data for this study were obtained from the National Health Insurance Services Sampled Cohort database. This study included patients with four types of cancer (top four cancer incidence in 2020): gastric (3353), colorectal (2915), lung (1351), and thyroid (5158) cancer. The latent class mixed model was used to investigate cancer care patterns, and multiple regression or survival analysis was performed to examine medical cost, length of stay (LOS), and mortality. Results The patterns in each cancer type were classified into two to four classes, namely, mainly visited clinics or hospitals, mainly visited general hospitals, mainly visited tertiary hospitals (MT), and tertiary to general hospitals through trajectory modeling based on the utilization of cancer care. Compared to the MT pattern, other patterns were generally associated with higher cost, LOS, and mortality. Conclusion The patterns found in this study may be a more realistic way of defining patients with cancer in South Korea compared to previous studies, and its association‐related outcomes may be used as a basis to address problems in the healthcare system and prepare alternatives for patients with cancer. Future studies should review cancer care patterns related to other factors such as regional distribution.

ABSTRACTTamoxifen (Tam) has long been a top treatment option for breast cancer patients, but the challenge of eliminating cancer recurrence remains. Here, we identify a signalling pathway involving ELOVL2, ELOVL2-AS1, and miR-1233-3p, which contributes to drug resistance in Tam-resistant (TamR) breast cancer. ELOVL2-AS1, a long noncoding RNA, was significantly upregulated by its antisense gene, ELOVL2, which is known to be downregulated in TamR cells. Additionally, ELOVL2-AS1 underwent the most hypermethylation in MCF-7/TamR cells. Furthermore, patients with breast cancer who developed TamR during chemotherapy had significantly lower expression of ELOVL2-AS1 compared to those who responded to Tam. Ectopic downregulation of ELOVL2-AS1 by siRNA both stimulated cancer cell growth and deteriorated TamR. We also found that ELOVL2-AS1 sponges miR-1233-3p, which has pro-proliferative activity and elevates TamR, leading to the activation of potential target genes, such as MYEF2, NDST1, and PIK3R1. These findings suggest that ELOVL2-AS1, in association with ELOVL2, may contribute to the suppression of drug resistance by sponging miR-1233-3p in breast cancer.

Abstract There is a lack of research focused on understanding the different characteristics and healthcare utilization of metastatic breast cancer patients by palliative care use. This study aims to investigate trend of in-patient palliative care and its association with healthcare utilization among hospitalized metastatic breast cancer patients in the US. National Inpatient Sample (NIS) was used to identify nationwide metastatic breast cancer patients (n = 5209, weighted n = 25,961) from 2010 to 2014. We examined the characteristics of the study sample by palliative care and its association with healthcare utilization, measured by discounted hospital charges and length of stay. Multivariable survey regression models were used to identify predictors. Among 26,961 breast cancer patients, 19.0% had palliative care. Percentage of receiving palliative care during the period were gradually increased. Social factors including race, insurance types were also associated with a receipt of palliative care. Survey linear regression results showed that patients with palliative care were associated with 31% lower hospital charges, however, length of stays were not significantly associated. This study found evidence of who was associated with the receipt of palliative care and its relationship with healthcare utilization. This study also emphasizes the importance of receiving palliative care in patients with breast cancer, paving the way for future research into ways to improve palliative care in cancer patients. This study also found social differences and gave evidence of programs that could be used to help vulnerable groups in future health policy decisions.

Since the description of age-associated or autoimmune-associated B cells (ABCs), there has been a growing interest in the role of these cells in autoimmunity. ABCs are differently defined depending on the research group and are heterogenous subsets. Here, we sought to characterize ABCs in Sle1/2/3 triple congenic (TC) mice, which is a well accepted mouse model of lupus. Compared to follicular (FO) B cells, ABCs have many distinct functional properties, including antigen presentation. They express key costimulatory molecules for T cell activation and a distinct profile of cytokines. Moreover, they exhibit an increased capacity for antigen uptake. ABCs were also compared with germinal center (GC) B cells, which are antigen activated B cell population. There are several phenotypic similarities between ABCs and GC B cells, but GC B cells do not produce proinflammatory cytokines or take up antigen. While T cell proliferation and activation is induced by both FO B and ABCs in an antigen-dependent manner, ABCs induce stronger T cell receptor signaling in naïve CD4+ T cells and preferentially induce differentiation of T follicular helper (Tfh) cells. We found that ABCs exhibit a distinct transcriptomic profile which is focused on metabolism, cytokine signaling and antigen uptake and processing. ABCs exhibit an increase in both glycolysis and oxidative phosphorylation compared to FO B cells. Treatment of ABCs with metformin suppresses antigen presentation by decreasing antigen uptake, resulting in decreased Tfh differentiation. Taken together, these findings define a fundamental connection between metabolism and function within ABCs.

Objectives: We aimed to investigate the association between fragmented cancer care in the early phase after cancer diagnosis and patient outcomes using national insurance claim data.Methods: We identified National Health Insurance beneficiaries diagnosed with lung cancer in South Korea from 2010 to 2014. We included 1,364 lung cancer patients with reduced immortal time bias and heterogeneity. We performed multiple regression analysis using a generalized estimate equation with a gamma distribution for medical expenditures.Results: Among the 1,364 patients with lung cancer, 12.8% had fragmented cancer care. Healthcare costs were higher in fragmented cancer care for both during diagnosis to 365 days and diagnosis to 1,825 days. Linear regression results showed that fragmented cancer care was associated with 1.162 times higher costs during the period from diagnosis to 365 days and 1.163 times the cost for the period from diagnosis to 1,825 days.Conclusion: We found fragmented cancer care is associated with higher medical expenditure. Future health policy should consider the limitation of patients’ free will when opting for fragmented cancer care, as there are currently no control mechanisms.

Abstract Background We aimed to investigate the association between fragmented cancer care in the early phase after cancer diagnosis and patient outcomes using national insurance claim data. Methods From a nationwide sampled cohort database, we identified National Health Insurance beneficiaries diagnosed with gastric cancer (ICD-10: C16) in South Korea during 2005–2013. We analyzed the results of a multiple logistic regression analysis using the generalized estimated equation model to investigate which patient and institution characteristics affected fragmented cancer care during the first year after diagnosis. Then, survival analysis using the Cox proportional hazard model was conducted to investigate the association between fragmented cancer care and five-year mortality. Results Of 2879 gastric cancer patients, 11.9% received fragmented cancer care by changing their most visited medical institution during the first year after diagnosis. We found that patients with fragmented cancer care had a higher risk of five-year mortality (HR: 1.310, 95% CI: 1.023–1.677). This association was evident among patients who only received chemotherapy or radiotherapy (HR: 1.633, 95% CI: 1.005–2.654). Conclusions Fragmented cancer care was associated with increased risk of five-year mortality. Additionally, changes in the most visited medical institution occurred more frequently in either patients with severe conditions or patients who mainly visited smaller medical institutions. Further study is warranted to confirm these findings and examine a causal relationship between fragmented cancer care and survival.

Abstract Objective The benefits of palliative care for cancer patients were well developed; however, the characteristics of receiving palliative care and the utilization patterns among lung cancer patients have not been explored using a large-scale representative population-based sample. Methods The National Inpatient Sample of the United States was used to identify deceased metastatic lung cancer patients (n = 5,068, weighted n = 25,121) from 2010 to 2014. We examined the characteristics of receiving palliative care use and the association between palliative care and healthcare utilization, measured by discounted hospital charges and LOS (length of stay). The multivariate survey logistic regression model (to identify predictors for receipts of palliative care) and the survey linear regression model (to measure how palliative care is associated with healthcare utilization) were used. Results Among 25,121 patients, 50.1% had palliative care during the study period. Survey logistic results showed that patients with higher household income were more likely to receive palliative care than those in lower-income groups. In addition, during hospitalization, receiving palliative care was associated with11.2% lower LOS and 28.4% lower discounted total charges than the non-receiving group. Conclusion Clinical evidence demonstrates the benefits of palliative care as it is associated with efficient end-of-life healthcare utilization. Health policymakers must become aware of the characteristics of receiving the care and the importance of limited healthcare resource allocation as palliative care continues to grow in cancer treatment.

BackgroundThe focus of this study was to explore the association of patients’ rurality and other patient and hospital-related factors with in-hospital sepsis mortality to identify possible health disparities across United States hospitals.MethodsThe National Inpatient Sample was used to identify nationwide sepsis patients (n = 1,977,537, weighted n = 9,887,682) from 2016 to 2019. We used multivariate survey logistic regression models to identify predictors for how patients’ rurality is associated with in-hospital death.FindingsDuring the study periods, in-hospital death rates among sepsis inpatients continuously decreased (11.3% in 2016 to 9.9% in 2019) for all rurality levels. Rao-Schott Chi-Square tests demonstrated that certain patient and hospital factors had varied in-hospital death rates. Multivariate survey logistic regressions suggested that rural areas, minorities, females, older adults, low-income, and uninsured patients have higher odds of in-hospital mortality. Further, specific census divisions like New England, Middle Atlantic, and East North Central had greater in-hospital sepsis death odds.ConclusionRurality was associated with increased in-hospital sepsis death across multiple patient populations and locations. Further, rurality in New England, Middle Atlantic, and East North Central locations is exceptionally high odds. In addition, minority races in rural areas also have an increased odds of in-hospital death. Therefore, rural healthcare requires a more significant influx of resources and should also include assessing patient-related factors.

Abstract Background Although survival based outcomes of lung cancer patients have been well developed, institutional transition of cancer care, that is, when patients transfer from primary visiting hospitals to other hospitals, and mortality have not yet been explored using a large-scale representative population-based sample. Methods Data from the Korean National Elderly Sampled Cohort survey were used to identify patients with lung cancer who were diagnosed during 2005–2013 and followed up with for at least 1 year after diagnosis (3738 patients with lung cancer aged over 60 years). First, the authors examined the distribution of the study population by mortality, and Kaplan-Meier survival curves/log-rank test were used to compare mortality based on institutional transition of cancer care. Survival analysis using the Cox proportional hazard model was conducted after controlling for all other variables. Results Results showed that 1-year mortality was higher in patients who underwent institutional transition of cancer care during 30 days after diagnosis (44.2% vs. 39.7%, p = .027); however, this was not associated with 5-year mortality. The Cox proportional hazard model showed that patients who underwent institutional transition of cancer care during 30 days after diagnosis exhibited statistically significant associations with high mortality for 1 year and 5 years (1-year mortality, Hazard ratio [HR]: 1.279, p = .001; 5-year mortality, HR: 1.158, p = .002). Conclusion This study found that institutional transition of cancer care was associated with higher mortality among elderly patients with lung cancer. Future consideration should also be given to the limitation of patients’ choice when opting for institutional transition of care since there are currently no control mechanisms in this regard. Results of this study merit health policymakers’ attention.

Background: Ginsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anticancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse. Methods: LncRNAs whose promoter DNA methylation level was significantly altered by Rh2 were screened from methylation array data. The effect of STXBP5-AS1, miR-4425, and RNF217 on the proliferation and apoptosis of MCF-7 breast cancer cells was monitored in the presence of Rh2 after deregulating the corresponding gene. The ceRNA relationship between STXBP5-AS1 and miR-4425 was examined by measuring the luciferase activity of a recombinant luciferase/STXBP5-AS1 plasmid construct in the presence of mimic miR-4425. Results: Inhibition of STXBP5-AS1 decreased apoptosis but stimulated growth of the MCF-7 cells, suggesting tumor-suppressive activity of the lncRNA. MiR-4425 was identified to have a binding site on STXBP5-AS1 and proven to be downregulated by STXBP5-AS1 as well as by Rh2. In contrast to STXBP5-AS1, miR-4425 showed pro-proliferation activity by inducing a decrease in apoptosis but increased growth of the MCF-7 cells. MiR-4425 decreased luciferase activity from the luciferase/STXBP5-AS1 construct by 26%. Screening the target genes of miR-4425 and Rh2 revealed that Rh2, STXBP5-AS1, and miR-4425 consistently regulated tumor suppressor RNF217 at both the RNA and protein level. Conclusion: LncRNA STXBP5-AS1 is upregulated by Rh2 via promoter hypomethylation and acts as a ceRNA, sponging the oncogenic miR-4425. Therefore, Rh2 controls the STXBP5-AS1/miR-4425/RNF217 axis to suppress breast cancer cell growth.

This study presents rice husk silica-reinforced elastomer composites fabricated by wet compounding, exhibiting 10% higher dynamic friction coefficients than the reference composites made by conventional dry compounding. Depending on the fabrication method, the filler micro-dispersion was characterized to correlate the measured friction coefficients with the viscoelastic properties with respect to sliding velocity and substrate lubrication. The effect of viscoelastic properties of the elastomer composites on the adhesion and hysteresis friction coefficients was investigated based on the elastomer friction theory. It was found that the constructed friction master curves showed a reasonable correlation with the theory. This study demonstrates that the rice husk silica can be used as a reinforcing filler for sustainable tires. More importantly, the well-dispersed filler microstructures can ensure the higher friction coefficients of the elastomer composites on rough surfaces, improving the tire performances (e.g., wet traction, cornering, and acceleration) of the ever-growing electric vehicles and future mobility.

Abstract Background In Korea, the universal health system offers coverage to all members of society. Despite this, it is unclear whether risk of death from hepatocellular carcinoma (HCC) varies depending on income. We evaluated the impact of low income on HCC mortality. Methods The Korean National Health Insurance sampling cohort was used to identify new HCC cases (n = 7325) diagnosed between 2004 and 2008, and the Korean Community Health Survey data were used to investigate community-level effects. The main outcome was 5-year all-cause mortality risk, and Cox proportional hazard models were applied to investigate the individual- and community-level factors associated with the survival probability of HCC patients. Results From 2004 to 2008, there were 4658 new HCC cases among males and 2667 new cases among females. The 5-year survival proportion of males was 68%, and the incidence per person-year was 0.768; the female survival proportion was 78%, and the incidence per person-year was 0.819. Lower income was associated with higher hazard ratio (HR), and HCC patients with hepatitis B (HBV), alcoholic liver cirrhosis, and other types of liver cirrhosis had higher HRs than those without these conditions. Subgroup analyses showed that middle-aged men were most vulnerable to the effects of low income on 5-year mortality, and community-level characteristics were associated with survival of HCC patients. Conclusion Having a low income significantly affected the overall 5-year mortality of Korean adults who were newly diagnosed with HCC from 2004 to 2008. Middle-aged men were the most vulnerable. We believe our findings will be useful to healthcare policymakers in Korea as well as to healthcare leaders in countries with NHI programs who need to make important decisions about allocation of limited healthcare resources according to a consensually accepted and rational framework.

Follicular Th (Tfh) cells are key CD4+ Th cells involved in regulating B cell differentiation in the germinal center. Mice with conditional KO (CKO) of B lymphocyte-induced maturation protein-1 (BLIMP-1) expression in CD11chi DCs (Prdm1 CKO) spontaneously develop a lupus-like disease. We found an increase in the number of Tfh cells in secondary lymphoid organs in lupus-prone Prdm1-CKO mice. B cells stimulated with Tfh cells become Ab-secreting cells (ASCs); there was an increase in ASC differentiation mediated by Tfh cells from Prdm1-CKO mice compared with Tfh cells from control mice. This was mainly due to the increased expression of molecules within the IL-23/IL-17 pathway in Tfh cells from Prdm1-CKO mice. There was an increased frequency of IL-17A+ Tfh cells in Prdm1-CKO mice. These Tfh cells secrete IL-17A and an increased amount of IL-21. Furthermore, neutralizing IL-17A and IL-21 reduced ASC differentiation induced by Tfh cells. Lastly, we found the expression of IL-1β and IL-6 was increased in BLIMP-1–deficient DCs, which are key for Th17 induction. Altogether, the lack of BLIMP-1 expression in DCs induces not only an increased number of Tfh cells, but also functionally distinct Tfh cells that lead to increased ASC differentiation.

Background: Ginsenoside Rg3, a derivative of steroidal saponins abundant in ginseng, has a range of effects on cancer cells, including anti-cell proliferation and anti-inflammation activity. Here, we investigate two long noncoding RNAs (lncRNAs), STXBP5-AS1 and RFX3-AS1, which are hypomethylated and hypermethylated in the promoter region by Rg3 in MCF-7 cancer cells. Methods: The lncRNAs epigenetically regulated by Rg3 were mined using methylation array analysis. The effect of the lncRNAs on the apoptosis and proliferation of MCF-7 cells was monitored in the presence of Rg3 or Korean Red Ginseng (KRG) extract after deregulating the lncRNAs. The expression of the lncRNAs and their target genes was examined using qPCR and Western blot analysis. The association between the expression of the target genes and the survival rate of breast cancer patients was analyzed using the Kaplan-Meier Plotter platform. Results: STXBP5-AS1 and RFX3-AS1 exhibited anti- and pro-proliferation effects, respectively, in the cancer cells, and the effects of Rg3 and KRG extract on apoptosis and cell proliferation were weakened after deregulating the lncRNAs. Of the genes located close to STXBP5-AS1 and RFX3-AS1 on the chromosome, STXBP5, GRM1, RFX3, and SLC1A1 were regulated by the lncRNAs on the RNA and protein level. Breast cancer patients that exhibited a higher expression of the target genes of the lncRNAs had a higher metastasis-free survival rate. Conclusion: The current study is the first to identify lncRNAs that are regulated by the presence of Rg3 and KRG extract and that subsequently contribute to inhibiting the proliferation of cancer cells. Keywords: CpG methylation, ginsenoside Rg3, long noncoding RNA, Korean Red Ginseng

Malone antegrade continent enema (ACE) is a procedure in which an appendicostomy is performed to effectively control intractable fecal incontinence. In this procedure, spontaneous knotting of the enema catheter inside the cecum may occur, albeit rarely. In such a situation, the knot of the ACE catheter in the cecum could not be removed easily. Here, we aimed to report two cases of spontaneous knotting of the ACE catheter during routine ACE. Moreover, we aimed to discuss the mechanism of spontaneous knotting of the catheter during ACE, preventive methods, and methods to remove the knotted catheters.

IntroductionMedullary thyroid carcinoma (MTC) is a rare cancer that accounts for 5% of thyroid cancers. Serum calcitonin is a good biomarker for MTC, which is used for diagnosis, prognosis, and monitoring of recurrence. Calcitonin-negative MTC (CNMTC) is rare but confounds diagnostic and prognostic directions. This study introduces 19 cases of CNMTC in a single center.MethodFrom 2002 March to 2020 July, more than 76,500 patients had undergone thyroid surgery due to thyroid cancer at the Severance Hospital, and a total of 320 patients were diagnosed with MTC (0.4%). Serum calcitonin levels were obtained from every patient who was suspected with MTC. These patients had undergone either bilateral total thyroidectomy or unilateral thyroidectomy with central compartment lymph node dissection, and additional modified radical lymph node dissection if lateral lymph node metastasis was positive. Postoperative monitoring and out-patient clinic follow-up were performed with obtaining the serum calcitonin levels.ResultNineteen patients tested negative for calcitonin preoperatively (6%). The mean preoperative calcitonin level was 5.1pg/mL if undetectable level is regarded as 0pg/mL. Only two patients were males, and the female bias was significant (p = 0.017). No one except two patients with modified radical neck dissection showed central compartment lymph node metastasis. Every patient’s postoperative calcitonin level remained low. The median follow-up period was 71 months. There was no recurrence and only one fatality, and the overall survival rate was 95%.ConclusionSince incidence of CNMTC is not negligible, MTC should not be ruled out in the diagnostic phase even if serum calcitonin is negative in preoperative examination. We presented 19 cases of CNMTC whose prognosis in general were favorable. Markers of serum and immunohistochemical samples other than calcitonin should be actively examined.

Background/Aim We aimed to evaluate the efficacy of sending educational video clips via smartphone mobile messenger (SMM) on enhancing bowel preparation before colonoscopy. Methods This was a prospective, endoscopist-blinded, randomized controlled study. Patients in the SMM group received two video clips sent via SMM that explained the diet and regimen for bowel preparation, whereas those in the control group did not receive any video clips. We compared the quality of bowel preparation between the two groups, which was assessed by an endoscopist using the Ottawa scale. Results Between August and November 2014, 140 patients in the SMM group and 141 patients in the control group underwent colonoscopic examination. T he total Ottawa score of the SMM group was significantly lower than that of the control group (5.47±1.74 vs. 5.97±1.78, p=0.018). These results were particularly prominent in the younger age group; the total Ottawa score of patents in the SMM group aged

Background: Ginsenoside Rh2 has been known to enhance the activity of immune cells, as well as to inhibit the growth of tumor cells. Although the repertoire of genes regulated by Rh2 is well-known in many cancer cells, the epigenetic regulation has yet to be determined, especially for comprehensive approaches to detect methylation changes. Methods: The effect of Rh2 on genome-wide DNA methylation changes in breast cancer cells was examined by treating cultured MCF-7 with Rh2. Pyrosequencing analysis was carried out to measure the methylation level of a global methylation marker, LINE1. Genome-wide methylation analysis was carried out to identify epigenetically regulated genes and to elucidate the most prominent signaling pathway affected by Rh2. Apoptosis and proliferation were monitored to examine the cellular effect of Rh2. Results: LINE1 showed induction of hypomethylation at specific CpGs by 1.6–9.1% (p

Epinephrine is a hormone secreted primarily by medullary cells of the adrenal glands which regulates permeability of blood–brain barrier (BBB). Recent studies showed signaling by epinephrine/epinephrine receptor in T cells is involved in autoimmune diseases. Nevertheless, the production of epinephrine by T cells and its pathogenic function in T cells are not well investigated. Our results show that phenylethanol N-methyltransferase (PNMT), a rate-limiting enzyme of epinephrine synthesis, is specifically expressed in vitro in differentiated TH17 cells and in tissue-resident TH17 cells. Indeed, expression levels of enzymes involved in epinephrine production are higher in TH17 cells from animals after EAE induction. The induction of PNMT was not observed in other effector T cell subsets or regulatory T cells. Epinephrine producing TH17 cells exhibit co-expression of GM-CSF, suggesting they are pathogenic TH17 cells. To delineate the function of epinephrine-production in TH17 cells, we generated a TH17-specific knockout of tyrosine hydroxylase (Th) by breeding a Th-flox and a ROR-gt-CRE mouse (Th-CKO). Th-CKO mice are developmentally normal with an equivalent T lymphocyte number in peripheral lymphoid organs. Th-CKO mice also show an equivalent number of TH17 cells in vivo and following in vitro differentiation. To test whether epinephrine-producing TH17 cells are key for breaching the BBB, migration of T cells through mouse brain endothelial cells was investigated in vitro. Both epi+ wild-type and epi- TH17 cells migrate through an endothelial cell barrier. Mice were immunized with MOG peptide to induce experimental autoimmune encephalitis (EAE) and disease progression was monitored. Although there is a reduced infiltration of CD4+ T cells in Th-CKO mice, no difference in clinical score was observed between Th-CKO and wild-type control mice. Increased neutrophils were observed in the central nervous system of Th-CKO mice, suggesting an alternative pathway to EAE progression in the absence of TH17 derived epinephrine.

Background: Tamoxifen (tam) is widely used to treat estrogen-positive breast cancer. However, cancer recurrence after chemotherapy remains a major obstacle to achieve good patient prognoses. In this study, we aimed to identify genes responsible for epigenetic regulation of tam resistance in breast cancer. Methods: Methylation microarray data were analyzed to screen highly hypomethylated genes in tam resistant (tamR) breast cancer cells. Quantitative RT-PCR, Western blot analysis, and immunohistochemical staining were used to quantify expression levels of genes in cultured cells and cancer tissues. Effects of matrix metalloproteinase-1 (MMP1) expression on cancer cell growth and drug resistance were examined through colony formation assays and flow cytometry. Xenografted mice were generated to investigate the effects of MMP1 on drug resistance in vivo. Results: MMP1 was found to be hypomethylated and overexpressed in tamR MCF-7 (MCF-7/tamR) cells and in tamR breast cancer tissues. Methylation was found to be inversely associated with MMP1 expression level in breast cancer tissues, and patients with lower MMP1 expression exhibited a better prognosis for survival. Downregulating MMP1 using shRNA induced tam sensitivity in MCF-7/tamR cells along with increased apoptosis. The xenografted MCF-7/tamR cells that stably expressed short hairpin RNA (shRNA) against MMP1 exhibited retarded tumor growth compared to that in cells expressing the control shRNA, which was further suppressed by tam. Conclusions: MMP1 can be upregulated through promoter hypomethylation in tamR breast cancer, functioning as a resistance driver gene. MMP1 can be a potential target to suppress tamR to achieve better prognoses of breast cancer patients.

Proper expression of the transcription factor, Positive regulatory domain 1 (PRDM1), is required for maintaining homeostasis of human monocyte derived-dendritic cells (MO-DCs). The molecular mechanisms and gene targets of PRDM1 in B and T lymphocytes have been identified. However, the function of PRDM1 in dendritic cells (DCs) remains unclear. We investigate co-regulators of PRDM1 in MO-DCs identified by mass spectrometry (MS) and co-immunoprecipitation (Co-IP). Notably, non-POU domain-containing octamer-binding protein (NonO) was found to be a PRDM1 binding protein in the nucleus of MO-DCs. NonO is recruited to the PRDM1 binding site in the promoter region of IL-6. Knockdown of NonO expression by siRNA lessened suppression of IL-6 promoter activity by PRMD1 following LPS stimulation. While NonO binding to PRDM1 was observed in human myeloma cell lines, an effect of NonO on IL-6 expression was not observed. Thus, loss of NonO interrupted the inhibitory effect of PRDM1 on IL-6 expression in MO-DCs, but not plasma cells. Moreover, MO-DCs with low expression of PRDM1 or NonO induce an increased number of IL-21-producing TFH-like cells in vitro. These data suggest that low level of PRDM1 and NonO lead to enhanced activation of MO-DCs and the regulation of MO-DC function by PRDM1 is mediated through cell lineage-specific mechanisms.

Abstract To identify dysregulated genes by abnormal methylation and expression in breast cancer, we genome-wide analyzed methylation and expression microarray data from the Gene Expression Omnibus and the Cancer Genome Atlas database. One of the genes screened in silico, FLRT2, showed hypermethylation and downregulation in the cancer dataset and the association was verified both in cultured cell lines and cancer patients’ tissue. To investigate the role of FLRT2 in breast cancer, its expression was knocked down and upregulated in mammary cell lines, and the effect was examined through three levels of approach: pathway analysis; cell activities such as proliferation, colony formation, migration, and adhesion; target gene expression. The top pathway was “Cellular growth and proliferation”, or “Cancer”-related function, with the majority of the genes deregulated in a direction pointing to FLRT2 as a potential tumor suppressor. Concordantly, downregulation of FLRT2 increased cell proliferation and cell migration, while overexpression of FLRT2 had the opposite effect. Notably, cell adhesion was significantly decreased by FLRT2 in the collagen I-coated plate. Taken together, our results provide insights into the role of FLRT2 as a novel tumor suppressor in the breast, which is inactivated by hypermethylation during tumor development.

Purpose: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity in many countries, and it has high rate of hospital readmissions due to recurrent exacerbations of the disease. Many previous studies have suggested further examination of the factors that contribute to hospital readmissions of COPD patients. However, evidence on the effects of nurse staffing by registered nurses (RNs) on the readmission of COPD patients is lacking in Korea. The aim of our study was to evaluate the effects of nurse staffing on hospital readmissions of COPD patients. Methods: We used National Health Insurance claim data from 2002 to 2012. A total of 1,070 hospitals and 339,379 hospitalization cases were included in the analysis. We divided the number of RNs per 100 beds and the proportion of RNs on staff to one of three groups (Q1: low; Q2: moderate; Q3: high). A generalized estimating equation model was used to evaluate the associations between readmission and nurse staffing. Results: A higher number of RNs was associated with lower readmission rates of 8.9% (Q2) and 7.9% (Q3) respectively. A similar effect was observed as the proportion of RNs among the total nursing staff gradually increased, resulting in lower readmission rates of 7.7% (Q2) and 8.3% (Q3). Conclusions: Our results suggest notable positive effects of nurse staffing by RNs on patient outcomes. In addition, the magnitude of impact differed between different sizes of hospitals. Thus, human resource planning to solve staffing shortages should carefully consider the qualitative aspects of the nursing staff composition.

Ginsenoside Rg3 exerts antiproliferation activity on cancer cells by regulating diverse noncoding RNAs. However, little is known about the role of long noncoding RNAs (lncRNAs) or their relationship with competitive endogenous RNA (ceRNA) in Rg3-treated cancer cells. Here, a lncRNA (ATXN8OS) was found to be downregulated via Rg3-mediated promoter hypermethylation in MCF-7 breast cancer cells. SiRNA-induced downregulation of ATXN8OS decreased cell proliferation but increased apoptosis, suggesting that the noncoding RNA possessed proproliferation activity. An in silico search for potential ATXN8OS-targeting microRNAs (miRs) identified a promising candidate (miR-424-5p) based on its high binding score. As expected, miR-424-5p suppressed proliferation and stimulated apoptosis of the MCF-7 cells. The in silico miR-target-gene prediction identified 200 potential target genes of miR-424-5p, which were subsequently narrowed down to seven that underwent hypermethylation at their promoter by Rg3. Among them, three genes (EYA1, DACH1, and CHRM3) were previously known oncogenes and were proven to be oppositely regulated by ATXN8OS and miR-424-5p. When taken together, Rg3 downregulated ATXN8OS that inhibited the tumor-suppressive miR-424-5p, leading to the downregulation of the oncogenic target genes.

Purpose: The purpose of this study was to explain the health promotion behavior of Chinese international students in Korea using a structural equation model including acculturation factors. Method: A survey using self-administered questionnaires was employed. Data were collected from 272 Chinese students who have resided in Korea for longer than 6 months. The data were analyzed using structural equation modeling. Results: The p value of final model is .31. The fitness parameters of the final model such as goodness of fit index, adjusted goodness of fit index, normed fit index, non-normed fit index, and comparative fit index were more than .95. Root mean square of residual and root mean square error of approximation also met the criteria. Self-esteem, perceived health status, acculturative stress and acculturation level had direct effects on health promotion behavior of the participants and the model explained 30.0% of variance. Conlcusions: The Chinese students in Korea with higher self-esteem, perceived health status, acculturation level, and lower acculturative stress reported higher health promotion behavior. The findings can be applied to develop health promotion strategies for this population.

Se abordan las diferencias de género como clave para la reducción de la brecha desalud. Este estudio se plantea describir las diferencias de género en salud autoinformada enCorea del Sur y Estados Unidos. Un total de 33.240 participantes de los KNHNES y 39.646 de laNHNES se incluyeron en el estudio. Se realizó un análisis de regresión logística múltiple paraidentificar las diferencias de género en salud autoinformada. Ésta fue calificada como pobre por el 18,8% y 16,3% de los participantes en Corea del Sur y en los Estados Unidos, respectivamente.Los resultados indicaron que las mujeres de Corea del Sur tienen mayor riesgo de mala saludautoinformada, difiriendo de las mujeres estadounidenses. El grupo de edad 20-39 a˜nos tuvoun mayor riesgo de mala salud autoinformada, tanto en Corea del Sur como en Estados Unidos.Se sugiere que los roles de género tradicionales de Corea del Sur afectan negativamente alas mujeres. Por lo tanto, el bienestar de Corea del Sur debe ser mejorado para reducir estasbrechas de salud entre países mediante la aplicación de leyes que tengan en cuenta el géneroy el grupo de edad de los beneficiarios.

Cold atmospheric plasma (CAP) can induce cancer cell death. The majority of gene regulation studies have been biased towards reactive oxygen species (ROS) among the physicochemical components of CAP. The current study aimed to systemically determine the distribution of target genes regulated by the ROS and non-ROS constituents of CAP. Genome-wide expression data from a public database, which were obtained after treating U937 leukemia and SK-mel-147 melanoma cells with CAP or H2O2, were analyzed, and gene sets regulated by either or both of them were identified. The results showed 252 and 762 genes in H2O2-treated U937 and SK-mel-147 cells, respectively, and 112 and 843 genes in CAP-treated U937 and SK-mel-147 cells, respectively, with expression changes higher than two-fold. Notably, only four and two genes were regulated by H2O2 and CAP in common, respectively, indicating that non-ROS constituents were responsible for the regulation of the majority of CAP-regulated genes. Experiments using ROS and nitrogen oxide synthase (NOS) inhibitors demonstrated the ROS- and reactive nitrogen species (RNS)-independent regulation of PTGER3 and HSPA6 when U937 cancer cells were treated with CAP. Taken together, this study identified CAP-specific genes regulated by constituents other than ROS or RNS and could contribute to the annotation of the target genes of specific constituents in CAP.

CD4+ follicular helper T (Tfh) cells constitute a subset of effector T cells that participate in the generation of high-affinity humoral responses. They express the chemokine receptor CXCR5 and produce the cytokine IL-21, both of which are required for their contribution to germinal center formation. Uncontrolled expansion of Tfh cells is observed in various mouse models of systemic autoimmune diseases and in patients with these diseases. In particular, the frequency of circulating Tfh is correlated with disease activity and anti-DNA antibody titer in patients with systemic lupus erythematosus. Recent studies reveal functional diversity within the Tfh population in both humans and mice. We will summarize here the molecular mechanisms for Tfh cell generation, survival and function in both humans and mice, and the relationship between Tfh cells and autoimmune disease in animal models and in patients.

Since 2011, specialty hospitals in South Korea have been known for providing high- quality care in specific clinical areas. Much research related to specialty hospitals and their performance in many such areas has been performed, but investigations about their performance in obstetrics and gynecology are lacking. Thus, we aimed to compare specialty vs. non-specialty hospitals with respect to mode of obstetric delivery, especially the costs and length of stay related to Cesarean section (CS) procedures, and to provide evidence to policy-makers for evaluating the success of hospitals that specialize in obstetric and gynecological (OBGYN) care.We obtained National Health Insurance claim data from 2012 to 2014, which included information from 418,141 OBGYN cases at 214 hospitals. We used a generalized estimating equation model to identify a potential association between the likelihood of CS at specialty hospitals compared with other hospitals. We also evaluated medical costs and length of stay in specialty hospitals according to type of delivery.We found that 150,256 (35.9%) total deliveries were performed by CS. The odds ratio of CS was significantly lower in specialty hospitals (OR: 0.95, 95% CI: 0.93-0.96compared to other hospitals Medical costs (0.74%) and length of stay (1%) in CS cases increased in specialty hospitals, although length of stay following vaginal delivery was lower (0.57%) in specialty hospitals compared with other hospitals.We determined that specialty hospitals are significantly associated with a lower likelihood of CS delivery and shorter length of stay after vaginal delivery. Although they are also associated with higher costs for delivery, the increased cost could be due to the high level of intensive care provided, which leads to improve quality of care. Policy-makers should consider incentive programs to maintain performance of specialty hospitals and promote efficiency that could reduce medical costs accrued by patients.

Objectives: A rapid increase in the population of migrant workers in Korea has brought new challenges regarding the possible effects of acculturation on health. The purpose of this study was to examine the influence of acculturation- and work-related psychosocial factors on work-related musculoskeletal disorders among migrant female workers living in Korea. Methods: A cross-sectional survey design was used. A translated, structured questionnaire was administrated to 156 southeastern Asian female full-time workers living in Korea. Results: About 35% of the participants experienced some type(s) of work-related musculoskeletal disorder(s), which were more prevalent in Vietnamese women than in Thai and Filipino women. Women who preferred to maintain their own heritage and to reject the host country heritage were at risk for work-related musculoskeletal disorders. Conclusion: Acculturation strategy and nationality were found to be significant factors associated with work-related musculoskeletal disorders. Health professionals need to accommodate acculturation contexts into risk assessment and intervention development for work-related musculoskeletal disorders separately for different nationalities.

Despite the concern of replacement disease, notably by serotype 19A after 7-valent conjugate vaccine (PCV7) use, serotype 19A was increasingly recognized in Korean children before the introduction of PCV7. To understand the dynamics of serogroup 19 prevalence from 1991–2006, we serotyped 538 pediatric pneumococcal isolates. Serogroup 19 isolates (n = 126) were characterized by antimicrobial drug susceptibility, presence of mefA/ermB, and multilocus sequence typing. Overall, the proportion of serotype 19A isolates increased but serotype 19F decreased. Among children

The disease burden is increasing for chronic obstructive pulmonary disease (COPD) due to increasing of the growth rate of prevalence and mortality. But the empirical researches are a little for COPD that studied the association between continuity of care and death and about predictors effect on mortality.To investigate the association between continuity of care (COC) and chronic obstructive pulmonary disease (COPD) mortality and to identify other mortality-related factors in COPD patients.We conducted a longitudinal, population-based retrospective cohort study in adult patients with COPD from 2002 to 2012 using a nationwide health insurance claims database. The study sample included individuals aged 40 years and over who developed COPD in 2005 and survived until 2006. We performed a Cox proportional hazard regression analysis with COC analyzed as a time-dependent covariate.Of the 3,090 participants, 60.8% died before the end of study (N = 1,879). The median years of survival for individuals with high COC (COC index≥0.75) was 3.92, and that for patients with low COC (COC index

Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05) by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

Aberrant methylation of specific CpG sites at the promoter is widely responsible for genesis and development of various cancer types. Even though the microarray-based methylome analyzing techniques have contributed to the elucidation of the methylation change at the genome-wide level, the identification of key methylation markers or top regulatory networks appearing common in highly incident cancers through comparison analysis is still limited. In this study, we in silico performed the genome-wide methylation analysis on each 10 sets of normal and cancer pairs of five tissues: breast, colon, liver, lung, and stomach. The methylation array covers 27,578 CpG sites, corresponding to 14,495 genes, and significantly hypermethylated or hypomethylated genes in the cancer were collected (FDR adjusted p-value 0.3). Analysis of the dataset confirmed the methylation of previously known methylation markers and further identified novel methylation markers, such as GPX2, CLDN15, and KL. Cluster analysis using the methylome dataset resulted in a diagram with a bipartite mode distinguishing cancer cells from normal cells regardless of tissue types. The analysis further revealed that breast cancer was closest with lung cancer, whereas it was farthest from colon cancer. Pathway analysis identified that either the "cancer" related network or the "cancer" related bio-function appeared as the highest confidence in all the five cancers, whereas each cancer type represents its tissue-specific gene sets. Our results contribute toward understanding the essential abnormal epigenetic pathways involved in carcinogenesis. Further, the novel methylation markers could be applied to establish markers for cancer prognosis.

Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3'UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.

Human lactoferrin (LF) is a multifunctional protein involved in immunomodulation, cellular growth, and differentiation. In addition to its secreted form (sLF), an alternative form (ΔLF) lacking the signal sequence has been found to be downregulated in cancer. Although the signaling pathways mediated by LF have been studied in a few cell models, there have been no relevant systemic approaches. Therefore, this study was carried out to identify and compare signaling networks provoked by the two LF isoforms. For this, the two forms were overexpressed in HEK293 cells using the Flp-In T-Rex system, after which genome-wide expression analysis of 18,367 genes was conducted. Pathway analysis of the genes showing altered expression identified pathways which are responsible for cell survival and apoptosis. In addition, the pathways mediated by the two LF forms were within distantly related networks. GPCR, PI3K complex, and POU5F1, which are involved in receptor-mediated pathways, were centered in the sLF network, whereas RIF1, NOS3, and RNPS1, which are involved in intracellular signaling, were centered in the ΔLF network. These results suggest that structural differences between the LF isoforms, mainly glycosylation, determine the fate of LF signaling. Furthermore, these findings provide information relating to the role of ΔLF which is downregulated during carcinogenesis.

MicroRNAs (miRNAs), 18-24 nt non-coding RNAs, are thought to play important roles in cell proliferation, differentiation, apoptosis, and development. Recent studies suggest that some of the known microRNAs map to a single genomic locale within a single polycistronic transcript. But the roles of the cluster remain to be known. In order to understand the role and mechanism of a cluster of miR-143 and miR-145 in esophageal squamous cell carcinoma (ESCC), the association of mature miR-143 and miR-145 expression with the risk for esophageal cancer was evaluated in ESCC patients with a case-control study, and target protein regulated by mature miRNA was analyzed in ESCC cell lines with 3'UTR luciferase reporter assay. The expression levels of miR-143 and miR-145 were determined in 110 pairs of esophageal cancer tissues and adjacent normal tissues using real-time reverse transcription PCR. The relative expression of miR-143 and miR-145 were statistically different between cancer tissues and matched controls. The combined expression of miR-143 and miR-145 was significantly associated with the risk for esophageal cancer. Meanwhile, the reduced expression of two miRNAs in tumor patient was supposed to have a trend of lymph node metastases. The co-expression pattern of miR-143 and miR-145 was analyzed with Pearson correlation. It showed a significant correlation between these two miRNAs expression both in tissues and tumor cell lines. 3'UTR luciferase reporter assay indicated that Fascin Homolog 1 (FSCN1) could be co-regulated by miR-143 and miR-145. The protein level of FSCN1 showed no significant linear correlation with miR-143 and miR-145 expression in ESCC cell lines with Western blotting analysis. In conclusion, since miR-143 and miR-145 could regulate oncogenic FSCN1 and take part in the modulation of metastases, the result suggested the combination variable of miR-143 and miR-145 as a potential biomarker for earlier diagnosis and prognosis of esophageal cancer.