Background: Interleukin (IL)-17E is a member of the IL-17 family, which induces IL-4, IL-5, IL-13, and eotaxin in experimental animals
via IL-17 receptor B (IL-17RB). The activation of IL-17RB ...amplifies allergic-type inflammatory responses by inducing Jun kinase (or JNK), p38 mitogen-activated protein kinase (or
MAPK), and nuclear factor-κB.
Objectives: We examined the association of polymorphisms in the IL-17RB gene with asthma susceptibility and investigated the effects of those polymorphisms on the transcription of various IL-17RB isoforms.
Methods: In total, 954 asthmatic patients or 265 healthy control subjects were screened for polymorphisms in IL-17RB by single-base extension. The messenger RNA expression IL-17RB in B-cell lines derived from patients was also measured by reverse transcription-polymerase chain reaction.
Results: Direct sequencing of 24 unrelated Korean DNA samples revealed 18 genetic variants, including four insertion/deletions and
14 single-nucleotide polymorphisms (SNPs). Six of the SNPs (â 1465G > A , + 5661G > A , + 6297T > C Y123Y, + 13797C > T , + 18661C > T , and + 18965G > A ) were used to screen a larger group of subjects. Intronic polymorphism + 5661G > A was significantly associated with the development of asthma (p = 0.001); moreover, a minor allele of IL-17RB + 5661G > A appeared at a lower frequency in the asthmatic patients than in the healthy control subjects (0.13 vs 0.19, respectively).
The IL-17RB messenger RNA expression in B cells homozygous for IL-17RB + 5661GG was significantly higher than that in B cells homozygous for IL-17RB + 5661AA (p = 0.002).
Conclusions: A rare allele of IL-17RB + 5661G > A may have a protective role against the development of asthma via regulation at the level of transcription. The SNPs identified
in this study may be used to develop markers to assess the risk of asthma.
Intravenous tissue plasminogen activator (IV-tPA) is pivotal for the treatment of acute ischemic stroke; however, the benefit of IV-tPA treatment declines rapidly soon after stroke onset.1 These ...results support intensive efforts to reduce both onset-totreatment (OTT) time and door-to-treatment (DTT) time and serve as a basis for establishing an in-hospital and prehospital stroke care system. As these efforts require substantial expenditures of labor and capital, more real-world data are needed to assess the effect of golden hour thrombolysis for acute ischemic stroke. Moreover, understanding the current status and secular changes in IV-tPA treatment will be important to establish an appropriate stroke care system in the future. Therefore, we investigated the effect of golden hour thrombolysis and secular changes in time-to-treatment variables for IV-tPA for acute ischemic stroke by analyzing a prospective registry of 16 stroke centers in South Korea. KCI Citation Count: 0
BACKGROUND AND PURPOSEBlood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with ...fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. METHODSThis multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). RESULTSOf 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. CONCLUSIONSFimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
Serum phosphorus concentrations are associated with an increased risk of cardiovascular disease (CVD) and mortality in patients with renal insufficiency. This association has also been reported in ...Western individuals without chronic kidney disease (CKD).
It is unclear, however, whether this correlation occurs in Korean individuals without CKD, who usually ingest less phosphorus than do Western individuals.
We reviewed the findings in 402 healthy Korean adults with a mean (±SD) age of 50.8 ± 8.5 y (n = 257 men and 145 women) and a glomerular filtration rate of 83.5 ± 14.1 mL/min, who underwent health screening with electron-beam computed tomography (EBCT). The study population was separated into 4 groups on the basis of the coronary calcium concentration (Agatston score: 0, >0 to ≤10, >10 to ≤100, and >100). Mean serum phosphorus concentrations, measured ≥10 y before EBCT, were compared.
Multivariate analysis showed that age (P = 0.001), male sex (P = 0.002), family history of CVD (P = 0.006), serum glucose (P = 0.003), and serum phosphorus >3.6 mg/dL (P = 0.008) were significant factors influencing the coronary calcification group with an Agatston score >100, when those with an Agatston score of 0 were considered as the reference group. Compared with the group with a serum phosphorus concentration ≤3.3 mg/dL, the OR of an Agatston score >100 in individuals with a serum phosphorus concentration >3.6 to ≤3.9 mg/dL was 3.89 (95% CI: 1.43, 10.63; P = 0.008) and in those with a serum phosphorus concentration >3.9 mg/dL was 3.17 (95% CI: 1.19, 8.41; P = 0.021).
A lower concentration of serum phosphorus within the normal range could be associated with less calcification of the coronary artery in Koreans with normal renal function.
Objective: FSTL1, an extracellular glycoprotein, is a novel myokine that is secreted by skeletal muscle. However, its functions in metabolism remain unclear, Adipose tissue is one of the important ...organs for maintaining energy homeostasis. FSTL1 is known to induce inflammatory response and inhibit insulin-mediated Akt signaling pathway, we aimed to investigate whether FSTL1 play metabolic roles in human adipose tissue. We hypothesized that FSTL1 increases lipolysis through its putative receptor DIP2A (Disco interacting protein 2 homolog A).
Methods: Human primary adipocytes were treated with recombinant FSTL1 in dose and time dependent manner. To determine its lipolytic activity, pHSL ser563,565,660, perilipin, AMPK, PKA were determined by western blot and the rate of free fatty acid was assessed. Expression of DIP2A was determined by PCR and western blot. DIP2A was knocked-down to examine whether it mediates metabolic effects of FSTL1.
Results: FSTL1 did not affect catecholamine-induced lipolysis via PKA. FSTL1, however, increased lipolysis through AMPK activation and, subsequently, HSL ser565 phosphorylation in dose dependent manner. It was found that DIP2A expression did not change during differentiation of human primary adipocyte, suggesting that it is not involved in adipocyte maturation.
Conclusion: FSTL1 increased basal lipolysis through AMPK activation. AMPK is well known sensor of the intracellular energy state and serves to regulate various signals. Its activation provides ATP by FA oxidation. Therefore, FSTL1 may play an important in the regulation of energy homeostasis. FSTL1 also has effect through DIP2A. These findings suggest that DIP2A plays important roles in FSTL1 mediated lipolysis.
Disclosure
C. Ahn: None. A. Choi: None. J. Kim: None. K. Park: None. S. Lee: None. J. Nam: None. S. Park: None. M. Kim: None. Y. Kim: None. J. Nam: None. S. Kang: None. J. Park: None.
Highlights • Direct access of stroke patients to hospitals offering intravenous thrombolytic therapy is compared to transfer of patients from non-thrombolysis centers. • Shorter onset-to-door time ...and better outcome in patients with acute ischemic stroke is demonstrated. • Implementation of regional stroke care programmings transporting stroke patients is recommended.
Several reports demonstrated that ethanol administration impairs the DNA synthesis in rat hepatocytes. Also, it has been demonstrated that prostaglandin (PG) helps prevent membrane damage by ...hepatotoxic chemicals. In this study, the authors examined PG's effects on the toxicity of ethanol in the primary culture of rat regenerations.
We examined two kinds of parameters, i.e., DNA synthesis and lipid peroxidation in the primary culture of rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method. The rate of DNA synthesis was determined by pulse-labelling cultured cells with 3H-thymidine. Incorporation of (3H)-thymidine was determined by liquid scintillation spectrophotometer. DNA content was measured by the fluorescence spectrophotometer. The lipid peroxidation was assayed with spectrophotometer.
The results were as follows: 1) PG family (PGA1, PGD2, PGE1, PGE2, PGG2a, PGI2 & Thromboxane B2) stimulated the DNA synthesis of hepatocytes (especially PGD2 and PGE1), 2) ethanol decreased DNA synthesis by clear dose-dependent manner, 3) the combined treatment of PGD2 or PGE1, prevents the decreasing of DNA synthesis, which was induced by ethanol, 4) in ethanol treatment, lipid peroxidation was decreased significantly, but PGD2, PGE1 and PGA1 were not affected, and 5) PGD2, PGE1 and PGA1 decreased lipid peroxidation with ethanol, significantly.
From these results, we concluded that PG could be useful for the treatment of degenerative liver disease and alcohol-induced liver disease in the assumption that further studies on the action mechanisms of PG will continue.
Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease with variable outcomes that are challenging to predict. A better understanding of the biology of ESCC recurrence is needed to ...improve patient care. Our goal was to identify small non-coding RNAs (sncRNAs) that could predict the likelihood of recurrence after surgical resection and to uncover potential molecular mechanisms that dictate clinical heterogeneity.
We developed a robust prediction model for recurrence based on the analysis of the expression profile data of sncRNAs from 108 fresh frozen ESCC specimens as a discovery set and assessment of the associations between sncRNAs and recurrence-free survival (RFS). We also evaluated the mechanistic and therapeutic implications of sncRNA obtained through integrated analysis from multiple datasets.
We developed a risk assessment score (RAS) for recurrence with three sncRNAs (microRNA (miR)-223, miR-1269a and nc886) whose expression was significantly associated with RFS in the discovery cohort (n=108). RAS was validated in an independent cohort of 512 patients. In multivariable analysis, RAS was an independent predictor of recurrence (HR, 2.27; 95% CI, 1.26 to 4.09; p=0.007). This signature implies the expression of ΔNp63 and multiple alterations of driver genes like PIK3CA. We suggested therapeutic potentials of immune checkpoint inhibitors in low-risk patients, and Polo-like kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase inhibitors in high-risk patients.
We developed an easy-to-use prognostic model with three sncRNAs as robust prognostic markers for postoperative recurrence of ESCC. We anticipate that such a stratified and systematic, tumour-specific biological approach will potentially contribute to significant improvement in ESCC treatment.
Post-treatment survivorship has not been extensively studied, despite long-standing evidence that after breast cancer treatment, women need continuing support to deal with their physical and ...psychosocial concerns.
The purpose of this experimental pilot study was to examine the quality of life (QOL) and symptom outcomes of a psychoeducational support program for women in the first year of post-breast cancer treatment survivorship.
: The sample consisted of 48 female breast cancer survivors randomly assigned to an intervention group (n = 25) and control group (n = 23). The psychoeducational support program consisted of individual face-to-face education, telephone-delivered health-coaching sessions, and small-group meetings. Study instruments were the Memorial Symptom Assessment Scale-Short Form and Functional Assessment of Cancer Therapy-Breast questionnaire.
Compared with the control group, survivors in the intervention group reported higher QOL overall and higher emotional well-being. The intervention group reported lower psychological symptom distress than the control group.
A psychoeducational support program may promote a better overall QOL and symptom experience in transition to survivorship among female breast cancer survivors.
Oncology nurses are in a position to provide education and support to assist breast cancer survivors in managing their symptoms and adjusting to life after primary treatment. Research to determine optimal strategies to improve breast cancer survivors' overall health and QOL is needed.
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