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.
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.
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.
Background 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). Methods 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. Results 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). Conclusions 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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Musculoskeletal disorder (MSD) is currently recognized as one of the most common occupational injuries for which nursing personnel in the medical service industry have been identified as a high-risk ...group. In this study, we explore the prevalence of MSD in various body parts as well as their risk factors among hospital nurses.
A cross-sectional descriptive design with stratified cluster sampling was used to collect data from 1,803 nurses. The survey included a demographic questionnaire, and Nordic Musculoskeletal Questionnaire.
The results showed that the greatest prevalence of MSD symptoms by body regions were in the right shoulder (85.8%), the left shoulder (80.9%), the neck (62.4%), the right wrist (62.2%) and the lower back (60.4%). Risk factors for shoulder discomfort includes department type, exercise habits, and age (p < .05). Risk factors for neck discomfort includes seniority in the current unit, "job title, and "history of MDS (p < .05). Risk factors for upper back discomfort includes age and seniority in the current unit (p < .05). Risk factors for lower back discomfort including seniority in the current unit, department type, and number of days worked per week (p < .05).
The results of this study can serve as a reference for nursing administration managers and decision-makers for reducing musculoskeletal discomfort among nurses and thereby achieving superior quality in clinical care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To compare the test-retest reliability and random measurement errors of the Barthel Index (BI) and modified Barthel Index (MBI) in patients with chronic stroke.
The intraclass correlation coefficient ...(ICC) and the minimal detectable change (MDC) were applied respectively to examine the test-retest reliability (about 2 weeks apart) and the random measurement errors. The MDC% was used to adjust the cut-off score for determining whether a real change had been achieved, if heteroscedasticity existed.
A total of 60 patients participated. The BI and MBI both had high ICCs (0.94 and 0.94, respectively) with small MDCs (16.2 and 15.4, respectively) and MDC%s (21.2% and 19.0%, respectively), indicating that both measures have comparable reliability in repeated assessments. However, moderate associations (r = −0.47 for the BI and −0.59 for the MBI) were found between the means of tests and retests and the absolute values of change scores, indicating heteroscedasticity. These findings suggest that a fixed MDC value is not appropriate for determining the real change in both measures because the amount of random measurement error varies with the patients' ADL function.
The MBI, which showed excellent test-retest reliability and relatively lower random measurement error than the BI, appears to be a better ADL measure. The MDC% adjusted value is recommended to determine whether the change scores are beyond random measurement error.
IMPLICATIONS FOR REHABILITATION
The MBI is recommended for clinical and research applications because it has better test-retest reliability and relatively lower random measurement error than those of the original BI.
The MDC% adjusted value is recommended to determine whether the change scores are beyond random measurement error when the MBI or the BI is used.
Novel dual inhibitors of histone deacetylase (HDAC) and heat-shock protein 90 (HSP90) are synthesized and evaluated. These compounds are endowed with potent HDAC and HSP90 inhibitory activities with ...IC50 values in nanomolar range with Compound 20 (HDAC IC50 = 194 nM; HSP90α IC50 = 153 nM) and compound 26 (HDAC IC50 = 360 nM; HSP90α IC50 = 77 nM) displaying most potent HDAC and HSP90α inhibitory activities. Both of these compounds induce HSP70 expression and down regulate HSP90 client proteins which play important roles in the regulation of survival and invasiveness in cancer cells. In addition, compounds 20 and 26 induce acetylation of α-tubulin and histone H3. Significantly, compounds 20 and 26 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-γ treated lung H1975 cells in a dose dependent manner. These findings suggest that dual inhibition of HDAC and HSP90 that can modulate immunosuppressive ability of tumor area may provide a better therapeutic strategy for cancer treatment in the future.
Display omitted
•N-alkyl-hydroxybenzoyl anilide hydroxamates show potent dual inhibition of HDAC and HSP90a.•Lead compounds 20 and 26 induce HSP70 expression and down regulate HSP90 client proteins.•Compounds 20 and 26 displayed their HDAC inhibitory effects due to increased acetylated α-tubulin and histone H3 levels.•Compounds 20 and 26 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-γ treated lung H1975 cells.
The cultural competence education programme for health professionals aimed to ensure that all people receive effective health care, particularly those from culturally diverse backgrounds.
The purpose ...of this study was to investigate the effect of a cultural competence educational course on nurses' self-assessment of their cultural competence.
A single-blind, randomised control trial design was employed.
Eligible nurses were recruited from a northern Taiwan medical centre with 2089 beds.
A permuted block of four was used to randomly assign participants to the experimental (n = 47) and control groups (n = 50). The educational course comprised four units and was conducted once weekly for four weeks, with each session lasting 3 h.
A significant group-time interaction was identified regarding self-learning cultural ability, verifying the education intervention's effect on self-learning cultural ability after a two-month intervention. In addition, a significant main effect over time was discovered for total cultural competence; there was no significant interaction effect.
The study provided evidence that an educational programme effectively improved cultural competence in clinical nurses. The results provide a reference for health care providers to design in-service cultural competence education for improving quality of care.
•Cultural competence in healthcare services caters to the patients' cultural needs.•Cultural competence is not an innate characteristic; it requires education.•Continuing education is crucial to foster cultural competence among nurses.
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