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To confront a disease like Alzheimer's disease having complex pathogenesis, development of multitarget-directed ligands has emerged as a promising drug discovery approach. In our endeavor towards the development of multitarget-directed ligands for Alzheimer's disease, a series of indoloquinoxaline derivatives were designed and synthesized. In vitro cholinesterase inhibition studies revealed that all the synthesized compounds exhibited moderate to good cholinesterase inhibitory activity. 6-(6-(Piperidin-1-yl)hexyl)-6H-indolo[2,3-b]quinoxaline 9f was identified as the most potent and selective BuChE inhibitor (IC50 = 0.96 µM, selectivity index = 0.17) that possessed 2 fold higher BuChE inhibitory activity compared to the commercially approved reference drug donepezil (IC50 = 1.87 µM). Moreover, compound 9f is also endowed with self-induced Aβ1-42 aggregation inhibitory activity (51.24% inhibition at 50 μM concentration). Some of the compounds of the series also displayed moderate anti-oxidant activity. To perceive a putative binding mode of the compound 9f, molecular docking studies were carried out, and the results pointed out significant interactions of compound 9f with the enzymes in the binding sites of cholinesterases as well as Aβ1-42. Additionally, compound 9f exhibited favorable in silico ADMET properties. Put together these findings project compound 9f as a potential multitarget-directed ligand in the direction of developing novel anti-AD drugs. Communicated by Ramaswamy H. Sarma.
Stigma is considered a major barrier to accessing healthcare services by female sex workers. Current knowledge of nurses' attitudes appears to imply a stigma toward female sex workers. But in-depth understanding of their perceptions is scarce. Furthermore, factors that inform a conceptual understanding of how this occurs are lacking.
The study aimed to explore nurses' attitudes toward female sex workers and factors affecting caring for female sex workers.
This was a qualitative study. A content analysis approach was adopted in analyzing the data.
Thirty-three practicing nurses participated in seven semi-structured focus group interviews and three key informants participated in three individual interviews in Hong Kong.
This study was approved by the Ethics Committee of one university in Hong Kong.
The findings revealed three themes (1) accept, stigmatize, or against sex work; (2) reluctance, hesitation, or willingness to care for female sex workers; and (3) factors affecting the care of female sex tude may have affected the provision of quality services, and to enhance the provision of sensitive non-discriminative services to female sex workers.The right to exercise choice is fundamental to the Universal Declaration of Human Rights, and it is assumed that all individuals generally enjoy freedom of choice in managing their health. Yet closer examination of this assumption calls into question its credibility and validity, especially with regard to maternal and child health around the globe. We argue that the concept of individual 'healthy choice,' particularly as applied to those with inadequate support and who are relatively disempowered, is flawed and unhelpful when considering the wider social, economic, and political forces underlying poor health. this website We instead propose that the realistic promotion of healthy choices requires acknowledging that agency lies beyond just the individual, and that individuals need to be supported through education and other structural and policy changes that facilitate a genuine ability to make healthy choices.
Most older people wish to live in the familiar surroundings of their own home until they die. Knowledge concerning dignity and dignity loss of home-dwelling older women living with incurable cancer should be a foundation for quality of care within municipal healthcare services. The informal caregivers of these women can help increase the understanding of sources related to dignity and dignity loss.
The aim of this study was to explore informal caregivers' perceptions of sources related to dignity and dignity loss in end-of-life of older home-dwelling women with incurable cancer.
The study was founded upon Gadamer's philosophical hermeneutics. In-depth interviews with 13 informal caregivers were carried out, and four participant observations were performed during home meetings.
The study was based on voluntary participation, informed consent, confidentiality and the opportunity to withdraw at any time. The Norwegian Social Science Data Services approved the study.
Three main sources important in preshe opportunity to maintain one's self-concept and control in life, preserved dignity, while feelings of existential loneliness led to dignity loss. On the relational level, being confirmed as worthy human beings promoted the women's dignity, whereas dignity loss was related to uncaring behaviours from healthcare professionals. On the societal level, individual decisions concerning travel situations and the place to stay when nearing end-of-life were of crucial importance. Constituting these women's living space, these perspectives should be emphasized in healthcare professionals' educational training and in the municipal end-of-life care of these patients.Plant homeodomain finger protein 8 (PHF8) has been reported to participate in cancer development and metastasis of various types of tumors. However, little is known about the functional mechanism of PHF8 in gastric cancer (GC). This study aimed to explore the PHF8 expression pattern and function, and the role of the MYC/miRNA/PHF8 axis in GC. PHF8 expression was upregulated in GC tissues and cells as measured using quantitative reverse transcription polymerase chain reaction and western blotting. PHF8 knockdown suppressed the proliferation, migration, and invasion of GC cells, as determined using the CCK-8 assay and Transwell assay. MicroRNA-22-3p targeted PHF8, as verified by a dual-luciferase reporter assay. MYC upregulated the protein expression of PHF8 but had no effect on PHF8 mRNA expression. MYC regulates PHF8 by affecting the stability of miR-22-3p. We identified a novel MYC/miR-22-3p/PHF8 regulatory axis in GC. Therefore, PHF8 may provide a new therapeutic target for patients with GC.
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