Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
Fibrosis is an exaggerated form of tissue repair that occurs with serious damage or repetitive injury and ultimately leads to organ failure due to the excessive scarring. Increased calcium ion entry ...through the TRPC6 channel has been associated with the pathogenesis of heart and glomerular diseases, but its role in renal interstitial fibrosis is unknown. We studied this by deletion of Trpc6 in mice and found it decreased unilateral ureteral obstruction-induced interstitial fibrosis and blunted increased mRNA expression of fibrosis-related genes in the ureteral obstructed kidney relative to that in the kidney of wild-type mice. Administration of BTP2, a pyrazol derivative known to inhibit function of several TRPC channels, also ameliorated obstruction-induced renal fibrosis and gene expression in wild-type mice. BTP2 inhibited carbachol-activated TRPC3 and TRPC6 channel activities in HEK293 cells. Ureteral obstruction caused over a 10-fold increase in mRNA expression for TRPC3 as well as TRPC6 in the kidneys of obstructed relative to the sham-operated mice. The magnitude of protection against obstruction-induced fibrosis in Trpc3 and Trpc6 double knockout mice was not different from that in Trpc6 knockout mice. Klotho, a membrane and soluble protein predominantly produced in the kidney, is known to confer protection against renal fibrosis. Administration of soluble klotho significantly reduced obstruction-induced renal fibrosis in wild-type mice, but not in Trpc6 knockout mice, indicating that klotho and TRPC6 inhibition act in the same pathway to protect against obstruction-induced renal fibrosis. Thus klotho and TRPC6 may be pharmacologic targets for treating renal fibrosis.
Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer ...(TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.
•Fucoidan from Laminaria japonica exerts antitumor effects.•Fucoidan suppresses proangiogenesis and micrometastasis in TNBC.•Fucoidan blocks MAPK and PI3K signaling in TNBC.
Abstract
The measurement of hypertensive patients’ stroke knowledge is an important stroke prevention indicator of health care service quality. The aim of this study was to develop a Chinese version ...of the Stroke Knowledge Test and examine its psychometric properties, reliability, and validity for hypertensive patients. A sample of 200 hypertensive patients completed the Chinese version of the Stroke Knowledge Test, and 30 of the participants were retested after 2 weeks. The final Chinese version of the Stroke Knowledge Test included 20 items with acceptable content validity (I-CVI = 0.88 ~ 1.00, S-CVI/Ave = 0.97). These items showed satisfactory internal reliability consistency (Kuder Richardson-20 = 0.62) and test–retest reliability was 0.77. The 40% of the difficulty index was in the acceptable range, and 25% was in the difficult range, as well as the 90% items overall values for discrimination were ranged from 0.2 to > 0.4. Known-group validity testing was performed based on the education level, and the result exhibited significant difference (F = 21.21, p < 0.001). The Chinese version of the Stroke Knowledge Test demonstrated acceptable psychometric properties, thus providing a new tool for the future care of hypertensive patients in Taiwan. It also could be as a reference for healthcare providers to educate hypertensive patients on stroke prevention.
Shared decision-making (SDM) is significantly associated with promoting the quality of end-of-life (EOL). The attitude of nurses toward the end of life can affect EOL care, but there are few ...SDM-related clinical learning programs focused on EOL. In this study, therefore, we evaluated the effectiveness of an EOL-simulation education program on attitudes toward SDM among nurses, using an objective structured clinical examination (OSCE). We used a quasi-experimental study design to evaluate nurses working at a medical center in Taiwan. We recruited 100 nurses and assigned them to an experimental group (n = 50) and a control group (n = 50). The experimental group received the SDM attitude (SDMA) cultivation program, and the control group did not. After the intervention, all participants were examined in an OSCE to assess the efficacy of their learning. A p value of.05 was considered statistically significant. The average score of the experimental group was higher than that of the control group in the dimensions "empathic communication" and "mastery learning", but these differences were not significant. SDMA score is significantly and positively correlated with SDMA global score, standardized patient survey (SPS) score, and SPS global score (r = .92, .56, and .50, respectively; p < .01). Simulations concerning EOL care that incorporate SDM components would be effective for training clinical nurses. This study can serve as a reference for nursing-administration managers who may consider designing SDM-related education programs to improve the quality of clinical nursing care.
The quality of nurses' work has a direct effect on patient health, and poor sleep has been positively associated with nurses' medical errors. The aim of this study was to investigate the relationship ...between quality of sleep and heart rate variability (HRV) among female nurses. A descriptive cross-sectional correlational study design was used in January 2014 to study female nurses (
= 393) employed in a medical center in Taiwan. Data were obtained from several questionnaires. HRV was analyzed with five-minute recordings of heart rate signals obtained using a Heart Rater SA-3000P. Approximately 96% of the participants self-reported a poor quality of sleep. Compared to non-shift nurses, significant decreases were found in total power (TP) and low-frequency HRV among shift-work nurses. However, negative correlations were found between sleep quality and HRV, including total power, low frequency, and the low frequency/high frequency ratio (
= -0.425,
< 0.05;
= -0.269, -0.266,
< 0.05). In a stepwise multiple regression analysis, 23.1% of variance in quality of sleep can be explained by TP and heart rate. The sleep quality of female nurses was poor and this affected their autonomic nervous system, which can contribute unfavorable consequences for their health.
This study reports the synthesis of a series of 2-aroylisoindoline hydroxamic acids employing N-benzyl, long alkyl chain and acrylamide units as diverse linkers. In-vitro studies led to the ...identification of N-benzyl linker-bearing compound (10) and long chain linker-containing compound (17) as dual selective HDAC6/HSP90 inhibitors. Compound 17 displays potent inhibition of HDAC6 isoform (IC50 = 4.3 nM) and HSP90a inhibition (IC50 = 46.8 nM) along with substantial cell growth inhibitory effects with GI50 = 0.76 μM (lung A549) and GI50 = 0.52 μM (lung EGFR resistant H1975). Compound 10 displays potent antiproliferative activity against lung A549 (GI50 = 0.37 μM) and lung H1975 cell lines (GI50 = 0.13 μM) mediated through selective HDAC6 inhibition (IC50 = 33.3 nM) and HSP90 inhibition (IC50 = 66 nM). In addition, compound 17 also modulated the expression of signatory biomarkers associated with HDAC6 and HSP90 inhibition. In the in vivo efficacy evaluation in human H1975 xenografts, 17 induced slightly remarkable suppression of tumor growth both in monotherapy as well as the combination therapy with afatinib (20 mg/kg). Moreover, compound 17 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-γ treated lung H1975 cells in a dose dependent manner suggesting that dual inhibition of HDAC6 and HSP90 can modulate immunosuppressive ability of tumor area.
Compound 17 downregulated PD-L1 expression in INF-γ treated H1975 lung cancer cells. Compound 17 in combination with afatinib enhanced antitumor efficacy. Display omitted
•1-Aroylisoindoline-hydroxamic acids as dual HDAC6/HSP90 inhibitors have been synthesized.•Compound 17 displays potent inhibition of HDAC6 isoform and HSP90a inhibition.•Compound 17 induced suppression of tumor growth in human H1975 xenografts.•Compound 17 downregulated PD-L1 expression in INF-γ treated H1975 lung cancer cells.•Compound 17 in combination with T cell immunotherapy might be worth investigating for treatment of cancer.
Abstract
Background
Shared decision making (SDM) is a patient-centered nursing concept that emphasizes the autonomy of patients. SDM is a co-operative process that involves information exchange and ...communication between medical staff and patients for making treatment decisions. In this study, we explored the experiences of clinical nursing staff participating in SDM.
Methods
This study adopted a qualitative research design. Semistructured interviews were conducted with 21 nurses at a medical center in northern Taiwan. All interview recordings were transcribed verbatim. Content analysis was performed to analyze the data.
Results
The findings yielded the following three themes covering seven categories: knowledge regarding SDM, trigger discussion and coordination, and respect of sociocultural factors.
Conclusions
The results of this study describe the experiences of clinical nursing staff participating in SDM and can be used as a reference for nursing education and nursing administrative supervisors wishing to plan and enhance professional nursing SDM in nursing education.
ObjectiveShared decision-making (SDM) enhances medical care, but an appropriate tool for evaluating nursing staff’s attitudes towards SDM in clinical practice is lacking. The objective of this study ...is to develop the Nursing Shared Decision-Making Attitude (NSDMA) scale and verify its psychometric properties.DesignInstrument design study.ParticipantsA sample of 451 nursing staff.InterventionThis study comprised two phases. In phase 1, qualitative research and expert content validity were adopted to develop the first draft of the scale. In phase 2, Taiwanese nursing staff were recruited through convenience sampling, and the sample was divided into a calibration sample and a validation sample. An objective structured clinical examination of SDM attitudes was administered to 100 nursing staff to determine the scale’s cut-off score.Main outcome measurementsExploratory factor analysis and confirmatory factor analysis were used to obtain the underlying factors of the NSDMA scale; McDonald’s omega value was used to determine the reliability; known-group validity was used to test the construct validity; and the receiver operating characteristic curve was adopted to determine the scale’s cut-off score.ResultsIn total, two factors were identified from the instrument results, which were termed ‘empathic communication’ and ‘mastery learning’. The McDonald’s omega value of the overall scale was 0.92. Known-group validity testing was performed based on the staff’s participation in SDM courses and experience of SDM, and the results exhibited significant differences (t=5.49, p<0.001; t=2.43, p<0.05). Based on the receiver operating characteristic curve, the optimal cut-off for SDM attitudes was determined as 48.5 points.ConclusionsThe NSDMA scale enables the evaluation of SDM attitudes among clinical nursing staff and nursing managers; the results may serve as a reference for incorporation of SDM into nursing policy formulation.
Elevated soluble (s) CD163 and free hemoglobin (Hb) levels predict fatty liver progression; however, the molecular mechanisms underlying Hb metabolism and liver injury remain undefined. We ...investigated the effects of endoplasmic reticular (ER) stress on red blood cell (RBC) rheology and free Hb recycling pathways. ER stress was induced in Sprague-Dawley rats by an intraperitoneal injection of tunicamycin (TM) (50, 100, and 200 μg/100 g body weight (BW)) or an intravenous injection of Hb (5 mg/100 g BW). A TM injection increased sCD163 levels, attenuated free Hb uptake, and maintained RBC aggregability. An Hb injection increased serum LVV-hemorphin-7 and total bilirubin levels, but this effect was suppressed by TM. A Western blot analysis showed that ER stress suppressed Hb degradation in the liver through downregulation of globin degradation proteins cathepsin D and glyoxalase-1, as well as heme degradation protein heme oxyganase-1 and keap-1 expression. An ER stress activator also increased the translocation of nuclear factor (NF)-κB (p65) and nuclear factor-erythroid 2-related factor 2 (Nrf2) to nuclei. In conclusion, ER stress triggers ineffective Hb metabolism via altering globin and heme iron degradation pathways. Inability to recycle and metabolize free Hb may underlie the association between iron dysfunction and liver injury.
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