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Cisplatin is one of the most common therapeutics used in treatments of several types of cancers. To enhance cisplatin lipophilicity and reduce resistance and side effects, a polyfluorinated bipyridine-modified cisplatin analogue, dichloro[4,4'-bis(2,2,3,3-tetrafluoropropoxy)methyl)-2,2'-bipryridine] platinum (TFBPC), was synthesized and therapeutic assessments were performed. TFBPC displayed superior effects in inhibiting the proliferation of several cisplatin-resistant human cancer cell lines, including MDA-MB-231 breast cancers, COLO205 colon cancers and SK-OV-3 ovarian cancers. TFBPC bound to DNA and formed DNA crosslinks that resulted in DNA degradation, triggering the cell death program through the PARP/Bax/Bcl-2 apoptosis and LC3-related autophagy pathway. Moreover, TFBPC significantly inhibited tumor growth in both animal models which include a cell line-derived xenograft model (CDX) of cisplatin-resistant MDA-MB-231, and a patient-derived xenograft (PDX) model of triple-negative breast cancers (TNBCs). Furthermore, the biopsy specimen from TFBPC-treated xenografts revealed decreased expressions of P53, Ki-67 and PD-L1 coupled with higher expression of cleaved caspase 3, suggesting TFBPC treatment was effective and resulted in good prognostic indications. No significant pathological changes were observed in hematological and biochemistry tests in blood and histological examinations from the specimen of major organs. Therefore, TFBPC is a potential candidate for treatments of patients suffering from TNBCs as well as other cisplatin-resistant cancers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Background: Culture influences personal health habits and behavior, and healthcare personnel possess different views of cultural perspectives. Currently, an appropriate instrument to assess cultural competence in clinical practice is limited. The present study aimed to develop and examine the psychometric properties of the Nursing Cultural Competence Scale (NCCS) for clinical nurses. Methods: Developing and assessing the scale was carried out in two phases: Phase I involved a qualitative research to explore the themes of nurses’ cultural competence and instrument development; Phase II established construct validity of the scale using a sample of 246 nurses in Taiwan. Data from the questionnaire were analyzed using exploratory factor analysis, confirmatory factor analysis, internal consistency and test-retest reliability. Analysis results were used to determine the reliability and validity of the developed scale. Results: The results showed four factors including cultural awareness ability, cultural action ability, cultural resources application ability, and self-learning cultural ability were generated by exploratory factor analysis, and these factors explained 62.0% of total variance. Cronbach’s α of the Nursing Cultural Competence Scale was .88, and test-retest reliability correlation was .70. Conclusions: The establishment of the tool will facilitate accurate monitoring of the cultural competence among nurses and nursing managers, which can inform the construction of nursing policies aimed at pledge cultural competence expansion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims and objectives. To examine the psychometric properties of the Menopausal Symptoms Distress Affecting Sleep Quality Scale. Background. Sleep disturbances are an extensive and common problem among menopausal women. However, no unique and specific scale has yet been developed to detect the inductive symptoms distresses that cause poor sleep quality for menopausal women. Design. A cross-sectional design. Methods. The Menopausal Symptoms Distress Affecting Sleep Quality Scale was based on in-depth interviews with menopausal women and literature review. Convenience sampling was employed. One hundred and fifty three women participated in this study. Exploratory factor analysis, concurrent validity and contrasting group validity were used to examine the validity of the Menopausal Symptoms Distress Affecting Sleep Quality Scale. Cronbach's a was conducted to test the reliability. The accuracy of the scale was analysed with the receiver operating characteristic from MED CALC version 10.4.8.0 software. The scale's sensitivity, specificity, positive and negative predictive value were analysed to locate the best cut-off point. Results. One factor was generated by Exploratory factor analysis, and this factor explained 49-07% of total variance. In addition, the Menopausal Symptoms Distress Affecting Sleep Quality Scale had significant positive correlations with the Greene Climacteric Scale and the self-evaluation of menopausal symptoms scale. Cronbach's a of the Menopausal Symptoms Distress Affecting Sleep Quality Scale was 0-89. Moreover, the diagnostic accuracy probability of the scale's receiver operating characteristic curve was 0-85. The best cut-off point was three with a sensitivity of 76% and a specificity of 87%. Conclusions. The Menopausal Symptoms Distress Affecting Sleep Quality Scale had good reliability and validity, as well as refined indicators for assessing the tool's accuracy. Relevance to clinical Practice. The Menopausal Symptoms Distress Affecting Sleep Quality Scale is easy to use, can quickly detect the sleep conditions of menopausal women who suffer from menopausal symptom distress, and provide efficient nursing interventions to relieve menopausal symptom distresses, and then improve sleep quality. [ABSTRACT FROM AUTHOR]

Multitarget agents simultaneously trigger molecules in functionally complementary pathways, and are therefore considered to have potential in effectively treating Alzheimer's disease (AD), which has a complex pathogenetic mechanism. In this study, the HDAC inhibitor core is incorporated into the acetylcholine esterase (ACE) inhibitor acridine–derived moiety and resulted in compounds that exhibited higher class IIa HDAC (4, 5, 7, and 9)- and class IIb HDAC6-inhibiting activity when compared to the pan-HDAC inhibitor SAHA in clinical practice. One of these compounds, 11b, displayed greater selectivity toward HDAC6 than other isoform enzymes. In contrast, the activity of compound 6a was selective toward class IIa HDAC and HDAC6. These two compounds exhibited strong activity against Aβ-aggregation as well as significantly disrupted Aβ-oligomer. Additionally, 11b and 6a strongly inhibited AChE. These experimental findings demonstrate that compounds 11b and 6a are HDAC-Aβ-aggregation-AChE inhibitors. Notably, they can enhance neurite outgrowth, but with no significant neurotoxicity. Further biological evaluation revealed the various cellular effects of multitarget compounds 11b and 6a , which have the potential to treat AD. Image 1 • Novel acridine-containing histone deacetylase inhibitors have been developed. • Structure-activity relationship of the resulting compounds has been established. • Several compounds are identified as multiple HDAC-Aβ-aggregation-AChE inhibitors. • Compounds 11b and 6a enhance neurite outgrowth without significant neurotoxicity. • Compound 11b can permeate blood-brain barrier. [ABSTRACT FROM AUTHOR]

Compounds 3j inhibited human placenta steroid sulfatse with IC 50 of 0.13 μM and displayed ireversible kinetic of K I 0.08 μM and K in cat 158 min−1. • Nineteen 3-aminocoumarin-7- O -sulfamates were designed and synthesized. • SAR revealed that modification at 3-position of coumarin resulted in enhancing STS inhibition. • Substitution at benzyl of 3-benzyl-aminocoumarin-7- O -sulfamates was crucial for STS inhibition. • Compound 3j inhibited STS from human placenta (IC 50 130 nM) and MCF-7 (IC 50 1.35 µM). Steroid sulfatase (STS) is a sulfatase enzyme that catalyzes the conversion of sulfated steroid precursors to free steroid. The inhibition of STS could abate estrogenic steroids that stimulate the proliferation and development of breast cancer, and therefore STS is a potential target for adjuvant endocrine therapy. In this study, a series of 3-benzylaminocoumarin-7- O -sulfamate derivatives targeting STS were designed and synthesized. Structure-relationship activities (SAR) analysis revealed that attachment of a benzylamino group at the 3-position of coumarin improved inhibitory activity. Compound 3j was found to have the highest inhibition activity against human placenta isolated STS (IC 50 0.13 μM) and MCF-7 cell lines (IC 50 1.35 µM). Kinetic studies found compound 3j to be an irreversible inhibitor of STS, with K I and k inact value of 86.9 nM and 158.7 min−1, respectively. [ABSTRACT FROM AUTHOR]

A series of C6-substituted N -hydroxy-2-quinolineacrylamides (3 – 15), with four types of bridging groups have been synthesized. Most of these compounds exhibit antiproliferative activity against A549 and HCT116 cells and Western blot analysis revealed that they are able to inhibit HDAC. Measurement of the HDAC isoform activity of ether-containing compounds showed that compound 9 has distinct HDAC6 selectivity, more than 300-fold over other isoforms. This paper describes the development of 6-aryloxy- N -hydroxy-2-quinolineacrylamides as potential HDAC6 inhibitors. [ABSTRACT FROM AUTHOR]

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 IC 50 values in nanomolar range with Compound 20 (HDAC IC 50 = 194 nM; HSP90α IC 50 = 153 nM) and compound 26 (HDAC IC 50 = 360 nM; HSP90α IC 50 = 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. Image 1 • 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. [ABSTRACT FROM AUTHOR]

• Quinoline – resorcinol hybrid constructs were designed and synthesized. • Compound 11 displayed potent cell growth inhibitory effects against PC-3 cell lines with GI 50 value of 0.14 µM. • The antiproliferative effects of 11 were mediated through Hsp90 chaperone inhibition. • Compound 11 demonstrated apoptosis inducing ability and caused G2M phase cell cycle arrest. • Docking studies revealed key interactions of 11 with amino acid residues of the HSP90 chaperone protein. The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11 , which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined. [ABSTRACT FROM AUTHOR]

Colon cancer is one of the most lethal cancers worldwide even with the significant progress made in screening techniques and therapeutic agents. Genetic mutations in tumors complicated the treatments, and the survival rate remains low for patients at late or metastatic stages. KRAS gene mutation which leads to failure of the EGFR targeted therapies stands for an example of the challenges in clinical sites. Therefore, development of novel agents for colon cancer treatment is in need. Natural and synthetic coumarin derivatives have been suggested with various biological activities with pharmacologic potential including anti-cancer capacity. Here in this study, five coumarin derivatives, include trifluoromethyl-, dimethoxy-, and/or nitro-substitutions at different positions, were synthesized. Their cancer inhibition potential was investigated in various cancer cell lines. Our data demonstrated that one nitro-coumarin derivate, 5,7-Dimethoxy-4-methyl-6-nitro-chromen-2-one, exhibits cytotoxicity specifically towards colon cancer cells under competitive EC 50. Our results showed that this compound can effectively suppress colon cancer cells harboring either wild type or mutant KRAS genes, and that it could inhibit short-term proliferation, long term proliferation, and migration capacities of cancer cells. Finally, we demonstrated that this coumarin derivate facilitates cancer cell death through activation of apoptosis pathway. Our results suggest that this coumarin derivate is a promising lead drug worth further investigation and development for future cancer treatment. • Coumarin derivatives were synthesized and examined in different human cancer cells. • A novel compound exhibited cytotoxicity specifically towards colon cancer cells. • It can inhibit short-term and long-term cancer cell proliferation. • It can suppress migration capacity of colon cancer cells. • It can facilitate cancer cell death through activation of apoptosis pathway. [ABSTRACT FROM AUTHOR]

Abstract We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC 50 value of 1.1 μM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC 50 value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6). Some key interactions of 9 with the amino acid residues of the active site of tubulin and with amino acid residues of HDAC 1 isoform have been figured out by molecular modeling. Compound 9 also demonstrated significant in vivo efficacy in the human non-small cell lung cancer A549 xenograft model as well as B-cell lymphoma BJAB xenograft tumor model. Graphical abstract Image 1 Highlights • A series of 1-Arylsulfonyl Indoline-Benzamides has been synthesized. • Compound 9 remarkably suppressed the growth of cancer cell lines. • The benzamide 9 displayed striking tubulin inhibition. • Compound 9 exhibited significant inhibitory potential against HDAC 1, 2 and 6. • Compound 9 also demonstrated significant in vivo efficacy. [ABSTRACT FROM AUTHOR]

The differences of basic attributes, health promotion behaviors, and quality of life between elderly males and females in Taiwan were compared. Several scales were used to examine the gender differences and the factors associated with quality of life. Regression analysis revealed that gender, education level, depression level, and healthy diet were key factors influencing the overall quality of life. The education level of females was lower, and their depression level was higher; however, females had healthier diets. With regards to their satisfaction in the quality of life, elderly males scored higher than females in both the physical and psychological domains. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Microtubule-targeting agents (MTA) have enjoyed significant clinical success for decades. However, several mechanisms may cause inactivation of such drugs, leading to acquired resistance in patients treated with them. Therefore, drugs containing a stilbene-like skeleton and possessing dual inhibitory activity may provide a new and differentiated treatment for patients to overcome challenging acquired resistance. A new compound (16c) displays promising anticancer activity with GI 50 of 22 ± 2 and 12 ± 0.1 nM in vincristine-resistant nasopharyngeal (KB-Vin) cancer cells and etoposide-resistant nasopharyngeal (KB-7D) cancer cells and is better than vincristine, etoposide, ABT-751, and MS-275. A mechanistic study revealed that 16c interferes with the cell cycle distribution and induces cell cycle arrest at the G2/M phase and severe mitotic spindle defects followed by apoptosis. In addition, it produces much more significant cytotoxicity than vincristine and etoposide in the corresponding resistant cells, indicating that it may be a promising candidate to overcome drug resistance in cancer cells. Compound 16c also displays inhibitory activity against HDAC 1 and HDAC 2 with IC 50 values of 1.07 μM, and 1.47 μM, respectively. These findings may lead to a new type of structural motif for future development of drugs that could overcome acquired resistance to MTAs. Image 1 • N-phenyl-4-(2-phenylsulfonamido)-benzamides act as Microtubule-targeting agents. • 16c displays promising anticancer activity against resistant cancer cells. • 16c induces cell cycle arrest at the G2/M phase. • 16c significantly inhibits microtubule polymerization. • 16c exhibited inhibitory potential against HDAC 1, 2 and 3. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of 21 tricyclic and tetracyclic sulfamates as STS inhibitors. • Design novel nonsteroidal tetracyclic coumarin skeleton for STS inhibition. • Para substitutions at the phenyl ring of tricyclic analogs gave the best STS inhibition. • 9e and 10c had k inact / K I of 28.6 and 19.1 nM−1min−1 on human STS, respectively. • Cytotoxicity of 9e (IC 50 of 0.65 µM) and 10c (IC 50 of 4.7 µM) on T-47D cells. Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin–based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with K I of 0.05 and 0.4 nM, and k inact / K I ratios of 28.6 and 19.1 nM−1min−1 on human placenta STS, respectively. [ABSTRACT FROM AUTHOR]

Aims and objectives: To investigate the distribution and risk factors associated with undiagnosed obstructive sleep apnoea among hypertensive patients. Background: Obstructive sleep Apnoea has been deemed a cardinal risk factor affecting cardiovascular event, and the condition is still frequently overlooked clinically. The lack of advanced diagnosis often causes hypertensive patients with obstructive sleep apnoea to miss opportunities for preventing chronic diseases. Design: A cross‐sectional design. Methods: A total of 215 hypertensive participants were recruited from the cardiovascular outpatients of medical centre in northern and middle Taiwan. The Chinese version of Pittsburgh Sleep Quality Index, the Chinese version of the Epworth Sleep Scale and a portable sleep monitoring device were used for data collection. Logistic regression analysis was conducted to identify the factors affecting hypertensive patients with obstructive sleep apnoea, and a multinomial logistic regression analysis was used to examine the major influence factors for each obstructive sleep apnoea severity level. Results: 81.9% of the hypertensive participants were found having obstructive sleep apnoea. Concerning to the obstructive sleep apnoea severity, 50.0% of participants had mild obstructive sleep apnoea. After controlling the confounding variables, the supine position (odds ratio, 1.04; 95% CI, 1.01–1.07), SO2 (odds ratio, 0.58; 95% CI, 0.38–0.89) and oxygen desaturation index (odds ratio, 2.70; 95% CI, 1.18–6.18) were significantly associated with obstructive sleep apnoea. Furthermore, severe obstructive sleep apnoea was significantly correlated with gender (odds ratio, 0.04; 95% CI, 0.00–0.66), excessive daytime sleepiness (odds ratio, 20.27; 95% CI, 1.58–26.97) and oxygen desaturation index (odds ratio, 4.05; 95% CI, 1.86–8.81). Conclusions: Nearly 82% of the hypertensive participants were found having undiagnosed obstructive sleep apnoea, and 80% of them were mild or moderate severity. Oxygen desaturation index, SO2 and the supine position were found to be major predictors for obstructive sleep apnoea. Remarkably, oxygen desaturation index was the most significant predictor for mild, moderate and severe obstructive sleep apnoea. Relevance to clinical practice: Healthcare providers should enhance their sensitivities to hypertensive patients at a high risk for obstructive sleep apnoea by actively assessing common obstructive sleep apnoea symptoms and providing strategies to alleviate obstructive sleep apnoea symptoms. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of 32 tricyclic sulfamates as STS irreversible inhibitors. • SAR studies revealed that adjacent halogen-bearing phenyl gave the best inhibition. • 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM against STS. • Cellular potency is significant correlated with covalent kinetics (k inact/ K I). Steroid sulfatase inhibitors block the local production of estrogenic steroids and are attractive agents for the treatment of estrogen-dependent cancers. Inspiration of coumarin-based inhibitors, we synthesized thirty-two 5-oxa-1,2,3,4-tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl sulfamates , focusing on the substitution derivatives on the adjacent phenyl ring and evaluated their abilities to block STS from human placenta and MCF-7 cells. SAR analysis revealed that the incorporation of chlorine at either meta and/or para position of the adjacent phenyl ring of the tricyclic skeleton enhanced STS inhibition. Di-substitutions at the adjacent phenyl ring were superior to mono and tri-substitutions. Further kinetic analysis of these compounds revealed that chloride-bearing compounds, such as 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM and k inact / K I ratios of 8.8–17.5 nM-1min-1, a parameter indicated for the efficiency of irreversible inhibition. We also used the docking model to illustrate the difference in STS inhibitory potency of compounds. Finally, the safety and anti-cancer activity of selected compounds 19 m , 19v , and 19w were also studied, showing the results of low cytotoxicity on NHDF cell line and being more potent than irosustat on ZR-75–1 cell, which was a hormone-dependent cancer cell line with high STS expression. [ABSTRACT FROM AUTHOR]

Various acidic anhydrides including cantharidin were converted into corresponding aminobenzylcantharidinimide 3a and analogous imides 3b∼k (at the ortho, meta, and para positions) with 35%∼87% yields by reacting with aminobenzylamines and triethylamine. The two methyl side chains of cantharidinimides 3ao, 3am, and 3ap, and related imides had more than two chiral centers; the lone pair of electrons of nitrogen displayed a different chemical shift and coupling constant in H-NMR spectra when the amino group of benzylamine was in the ortho position. These cantharidinimides had parent aniline, pyridine, and naphthalene plane structures, and the primary amine nucleophilicity and basicity might reflect the inductive electron's negative effect on chemical shifts. We prepared cantharidinimides by heating the reactants cantharidin 1a, aliphatic and aromatic acid anhydrides, primary benzylic amines, and aniline derivatives to ca. 200 °C with 3 mL of dry toluene, and 1∼2 mL of triethylamine in high-pressure sealed tubes (Buchi glasuster 0032) to produce cantharidinimides and their analogues in good yields. The para-aminobenzylic imides showed greater inhibition of nitric oxide (NO) synthesis by NO synthase (NOS) than did ortho- and meta-aminobenzylic imides. Compound 3fp, para-aminobenzylic norbonane-imide, had the most potent effect on inducible NOS among the tested compounds and showed 35% inhibition. [ABSTRACT FROM AUTHOR]

Background: Culture serves as an adhesive to bind the lives of people. There are no objective, useful tools to assess cultural competence and practice. In this study, we evaluated whether the cultural competence of nurses was strengthened through the Cultural Competence Cultivation Programme. Methods: A quasi-experimental research design was used to evaluate nurses working at a medical centre in Taiwan. They were randomly allocated into an experimental group (n = 47), which received the Cultural Competence Cultivation Programme, or a control group (n = 50), which did not receive the educational programme. After the intervention, learning efficacy of the participants was assessed using an Objective Structured Clinical Examination (OSCE). The research data were statistically analysed on SPSS. Results: The average score of the experimental group was significantly higher in the 'communication ability and skill' category. Furthermore, OSCE scores and Standardised Patient Survey assessment and total scores were significantly and positively correlated. Conclusion: The findings of this study can serve as a reference for designing future clinical education programmes. [ABSTRACT FROM AUTHOR]

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 (IC 50 = 4.3 nM) and HSP90a inhibition (IC 50 = 46.8 nM) along with substantial cell growth inhibitory effects with GI 50 = 0.76 μM (lung A549) and GI 50 = 0.52 μM (lung EGFR resistant H1975). Compound 10 displays potent antiproliferative activity against lung A549 (GI 50 = 0.37 μM) and lung H1975 cell lines (GI 50 = 0.13 μM) mediated through selective HDAC6 inhibition (IC 50 = 33.3 nM) and HSP90 inhibition (IC 50 = 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. Image 1 • 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 FROM AUTHOR]

A series of thiochromeno[2,3- c ]quinolin-12-one derivatives with various substitutions were synthesized and evaluated as topoisomerase (Topo) inhibitors. Six (8 , 10 , 12 , 14 , 19 , and 26) of 23 compounds showed strong inhibitory activities against Topo-mediated DNA relaxation and proliferation of five human cell lines including breast (MDA-MB-231, MDA-MB-468 and MCF7), colorectal (HCT116) and non-small cell lung (H1299) cancers. Among these, compounds 14 and 26 exhibited full inhibitory activities against Topo I at 3 μM and Topo IIα at 1 μM. Cancer cells treated with 26 accumulated DNA damage and were arrested at the G 2 /M phase. With time, cells proceeded to apoptosis, as revealed by increased amounts of cells with fragmented DNA and cleavage of caspase-8 and -9. In contrast, normal breast epithelial cells showed low sensitivity to 26. Taken together, our study identifies 26 as a potent Topo dual-inhibitor with low toxicity to normal cells, and elucidates that the terminal amino group of N -2-aminoethylamino or N -3-aminopropylamino at the 6th position and 8,10-di-halogen substituents on thiochromeno[2,3- c ]quinolin-12-one are critical for the Topo-inhibiting and cancer-killing activities. Image 1 • Six compounds identified as dual Topo inhibitors. • 26 exhibits the highest toxicity in five cancer cell lines but is less toxic in normal breast epithelial cells. • 26 traps Topo I and IIα on chromatin and suppresses their activities. • 26 triggers DNA damage, cell-cycle arrest at the G 2 /M phase, followed by apoptosis. [ABSTRACT FROM AUTHOR]

A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4–15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5 H -dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment. Image 1 • A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates has been synthesized. • The synthesized adducts were evaluated for their effects on vascular cognitive impairment. • Compound 13 increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy. • Compound 13 also increases the level of histone acetylation (H3K14 or H4K5). • Compound 13 could emerge as a potential HDAC inhibitor for the treatment of vascular cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: There are some limitations of standard chemotherapy for acute leukemia. Vincristine and doxorubicin are commonly used for acute leukemia, but they may induce serious side effects such as cardiomyopathy and neurotoxicity. Furthermore, chemotherapy resistance occurs more and more frequently. Therefore, effective treatment strategies are needed. Histone deacetylase 6 inhibition is considered as a potential therapeutic strategy for acute leukemia, since it is observed that HDAC6 is overexpressed in acute leukemia and regulates tumor survival. Combination therapy for cancer is used to minimize adverse drug effects, reduce drug dosage, enhance efficacy, and prevent drug resistance. In order to improve efficacy of chemotherapy agents of acute leukemia, this study will investigate the effects of combination MPT0G211, a novel histone deacetylase 6 inhibitor, with doxorubicin or vincristine on human acute leukemia cells. Results: MPT0G211 combined with doxorubicin induces DNA damage response on human acute myeloid leukemia cells. MPT0G211 can additionally increase Ku70 acetylation and release BAX to mitochondria. Ectopic expression of HDAC6 successively reversed the apoptosis triggered by the combined treatment. Moreover, co-treatment of MPT0G211 and vincristine may alter microtubule dynamics, triggering acute lymphoblastic leukemia cells arrest in mitotic phase followed by induction of the apoptotic pathway. Finally, MPT0G211 plus doxorubicin or vincristine can significantly improve the tumor growth delay in a tumor xenograft model. Conclusions: Collectively, our data highlighted that MPT0G211 in combination with chemotherapy drugs has significant anticancer activity, suggesting a novel strategy for the treatment of acute leukemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]