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1.
Exp Cell Res ; : 114259, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293523

RESUMEN

BACKGROUND: Alopecia areata (AA) is a chronic autoimmune disease. Th1/Th2 and Treg/Th17 cells and their cytokines are implicated in AA, and we explored their clinical significance in AA. METHODS: AA patients and healthy people (controls) were enrolled, with their Th1/Th2/Th17/Treg cell proportion changes and serum Th1 (INF-γ)/Th2 (IL-5, IL-6)/Th17 (IL-17, IL-22)/Treg (IL-35) cytokine levels assessed. AA patients were assigned into mild, moderate and severe alopecia according to Severity of Alopecia Tool (SALT). The relationship between alopecia severity and initial onset age, disease course, family/smoking/drinking history and sleep disorders was explored. Th1/Th2 and Treg/Th17 cells and their cytokine levels in AA patients with different severity levels were compared. The correlation between cytokine levels and SALT scores was analyzed using Spearman. Additionally, the changes of serum cytokine levels in inactive/active AA patients were compared. RESULTS: AA patients differed from controls in family history/smoking history/drinking history/sleep disorders. Peripheral blood Th1/Th2/Th17 cell proportions and INF-γ/IL-5/IL-6/IL-17/IL-22 levels increased, while Treg cell proportions and IL-35 level dropped. With higher alopecia severity, the proportions of Th1, Th2 and Th17 cells increased, and Treg cell proportion decreased. AA patients with mild/moderate alopecia had significant differences in IL-17 level. Serum INF-γ, IL-5, IL-17 and IL-22 levels were elevated, and IL-35 level dropped in severe AA patients versus moderate AA patients. CONCLUSION: Th1/Th2/Th17 cell proportions and serum INF-γ/IL-5/IL-6/IL-17/IL-22 levels in AA patients were up-regulated, while Treg cell proportion and IL-35 level were repressed. SALT scores were positively-correlated with serum IL-5/IL-17 levels. SALT scores were negatively-correlated with serum IL-35.

2.
Prostate ; 83(15): 1446-1457, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37545197

RESUMEN

BACKGROUND: Androgen deprivation therapy (ADT) is one of the main treatment modalities for prostate cancer (PCa); however, almost all patients treated with ADT eventually progress into castration-resistant PCa (CRPC). Although second-generation androgen receptor (AR) antagonists, such as enzalutamide, have been approved for CRPC treatment, AR signaling in CRPC cells is reactivated through multiple mechanisms, resulting in resistance to treatment and tumor progression with a very poor prognosis. The present study aimed to explore the anticancer effect of a treatment combining AR antagonist enzalutamide with AR degrader IU1 on PCa cells. METHODS: The joint effects of enzalutamide and IU1 on PCa cell proliferation and apoptosis and associated cell signaling were evaluated in vitro. Mechanistically, the ubiquitination level and half-life of AR were examined under the combination treatment. The binding of IU1 and enzalutamide to AR was further verified using cellular thermal shift analysis and isothermal dose-response curve fingerprinting. RESULTS: The combination of IU1 and three AR antagonists showed synergistic effects in different prostate cell lines. IU1 and enzalutamide synergistically promoted the degradation of AR and AR-V7 proteins, as well as suppressed the expression levels of AR and AR-V7 downstream target genes at the transcriptional and protein levels. The combination also synergistically blocked the PCa cell cycle and promoted apoptosis in PCa cell lines. Mechanistically, the combination promoted increased levels of AR ubiquitination. In CRPC cell lines and in the presence of increased androgen concentrations, enzalutamide was still able to bind AR competitively with androgens, reducing the stability of AR and thus promoting the degradation effect of IU1 on AR, synergistically producing an inhibitory effect on PCa cells. CONCLUSION: Taken together, our findings suggest that the combination of AR degrader and enzalutamide potentially represents a new therapeutic strategy for CRPC.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/patología , Andrógenos/metabolismo , Antagonistas de Andrógenos/uso terapéutico , Receptores Androgénicos/metabolismo , Benzamidas/uso terapéutico , Nitrilos/uso terapéutico , Antagonistas de Receptores Androgénicos/farmacología , Línea Celular Tumoral , Resistencia a Antineoplásicos
3.
J Nurs Scholarsh ; 54(1): 15-23, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34741408

RESUMEN

PURPOSE: To explore the experiences of nurses working in emergency departments in selecting and triaging patients during the COVID-19 pandemic. DESIGN: Descriptive phenomenology was applied in this study. METHODS: Data were collected from nurses working at hospitals in Indonesia using snowball sampling and telephone interviews. A total of 10 emergency nurses participated, and Colaizzi's method of data analysis was applied. FINDINGS: Six themes and 10 subthemes emerged. The main themes were "extreme challenges in triage," "feeling of responsibility under uncontrolled spread and infection," "physical and psychological exhaustion," "discovering strategies under difficult circumstances," "looking for positive reinforcement," and "optimism in togetherness." Nurses had to deal with the challenge of COVID-19 in the ED triage, interestingly so, the nurses they have shown the development of professional responsibility. Nurses are also experienced in finding patient selection and triage strategies and the sense of optimism that may influence strategy and practice during the COVID-19 pandemic. CONCLUSIONS: This findings identify nurses' experiences in dealing with the extreme challenges of emergency department triage as well as their associated strategies and optimism. CLINICAL RELEVANCE: Providing support to emergency nurses, improving emergency department triage, and community empowerment are suggested as strategies to improve nursing care during the COVID-19 pandemic.


Asunto(s)
COVID-19 , Enfermeras y Enfermeros , Servicio de Urgencia en Hospital , Humanos , Indonesia/epidemiología , Pandemias , SARS-CoV-2 , Triaje
4.
J Adv Nurs ; 76(3): 814-823, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31774190

RESUMEN

AIM: To examine female youth's intentions for safe sex with the relationship partners based on the extended theory of planned behaviour (TPB) model and explore the direct and indirect impact of parent-child communication about sex, peer interaction related to sexual issues, and exposure to sexually explicit materials on female youth's safe sexual behaviour intentions. DESIGN: A non-experimental, cross-sectional research design. METHODS: A convenience sampling was employed for data collection and 731 female youth aged 15-24 years old were recruited in 2013-2014. An anonymous, self-report structured questionnaire was used as a research instrument to collect participants' basic information and measure the internal and additional variables in the extended TPB model. RESULTS: The extended TPB model explained 42-45% of the total variance. Perceived behavioural control (PBC) and subjective norms had a positive effect on female youth's intentions for contraceptive use, condom use, and dual use with relationship partner; PBC was found to have the greatest influence. Among the additional variables in the extended TPB model, more parent-child communication about sex was found to lead to more positive dual use intentions. More peer interaction related to sexual issues was found to lead to less dual use intentions. CONCLUSIONS: To improve female youth's sexual health, the priorities are to reinforce their PBC and subjective norms and enhance parent-child communication about sex. Future efforts should strengthen sex education in families and schools and shape a social environment that facilitates safe sex. IMPACT: The extended TPB model can successfully predict female youth's safe sexual behaviour intentions. Empowering female youth to establish a sense of subjectivity and awareness of being a mature individual with physical autonomy, is importance for their sexual health.


Asunto(s)
Intención , Teoría Psicológica , Sexo Seguro , Adolescente , Femenino , Humanos , Parejas Sexuales , Adulto Joven
5.
Eur J Cancer Care (Engl) ; 28(5): e13113, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31180170

RESUMEN

OBJECTIVE: Fear of cancer recurrence (FCR) is the most commonly reported problem and unmet need among breast cancer survivors. The aim of this qualitative study was to explore the experience of recurrence fears among Taiwanese breast cancer survivors. METHODS: Three focus groups were included in this study. A purposive sampling technique was used to recruit 11 recurrence-free women at least 20 years of age from southern Taiwan who were diagnosed with breast cancer within the previous 2 years. Data were analysed and interpreted using content analysis. RESULTS: Three themes reflecting the experience of FCR were extracted from the transcript analyses: "Trapped in insecurity," "Suffering in silence," and "Pretending as if nothing happened." Participants endured a complex set of circumstances akin to silently walking the survival tightrope. Breast cancer survivors were still insecure and suffering, rather than celebrating survival, after the completion of treatment. Fear of cancer recurrence silently dominated their lives. CONCLUSIONS: An avoidance mindset and an unspoken FCR leave survivors insecure, resulting in a silent survival journey. These difficult thoughts and feelings that may impact the reconstruction of post-cancer life should be acknowledged. The development of appropriate survivorship care programs and emotional resilience regarding recurrence is needed for Taiwanese breast cancer survivors.


Asunto(s)
Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Miedo/psicología , Recurrencia Local de Neoplasia/psicología , Adulto , Femenino , Grupos Focales , Humanos , Persona de Mediana Edad , Investigación Cualitativa , Taiwán
6.
Mikrochim Acta ; 186(2): 123, 2019 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-30666555

RESUMEN

Colorimetric methods are described for the determination of ascorbic acid (AA) and alkaline phosphatase (ALP). Both assays are based on the inhibition of the peroxidase (POx)-like activity of Prussian Blue nanocubes (PB NCs) capped with citric acid. They catalyze the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) by H2O2 to produce a blue color with an absorption maximum at 652 nm. On addition of AA, the PB NCs are reduced to Prussian White (PW) which does not act as a POx mimic. This results in a decreased rate of the formation of the blue coloration whose intensity decreases with increasing concentration of AA. The assay allows AA to be quantified with a 35 nM detection limit (at 3σ/m). The hydrolysis of AA phosphate by ALP leads to the formation of AA which can be quantified by the above method. Based on this, the activity of ALP can be determined by measurement of the intensity of the blue coloration thus formed. The method can be used to determine the activity of ALP with a detection limit as low as 0.23 U·L-1. Graphical abstract Schematic presentation of a method for colorimetric determination of ALP activity. AA obtained by ALP-catalyzed hydrolysis of ascorbic acid phosphate (AAP) inhibits the intrinsic peroxidase-like activity of PB NCs by reducing Prussian Blue nanocrystals (PB NCs) to form inactive Prussian White (PW).

7.
J Clin Nurs ; 25(3-4): 543-54, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26818379

RESUMEN

AIMS AND OBJECTIVES: To examine the effects of an 8-week strengths-based perspective group intervention on hope, resilience and depression in Taiwanese women who left a violent intimate partner relationship. BACKGROUND: Studies on interventions for abused women have primarily focused on psychological problems. However, the effect of group intervention on the psychological strengths of abused women is still unknown. DESIGN: A two-group, quasi-experimental design using repeated measures was used in this study. METHODS: Twenty-nine Taiwanese women who left violent intimate partner relationships were assigned to two groups and five participants did not complete the study. The experimental group (n = 8) underwent an 8-week strengths-based perspective group intervention developed by the investigators; the control group (n = 16) received no intervention. The effects of the intervention on the participants' hope, resilience and depression levels were evaluated as a pretest, post-test 1 (8th week) and post-test 2 (12th week) and were compared. The Chinese version of the State Hope Scale, the 25-item Resilience Scale, and the Taiwanese Depression Questionnaire were used in this study. RESULTS: On the eighth and twelfth weeks after the strengths-based perspective group intervention, we found significantly lower scores on the depression scale in the experimental group. In the eighth week, participants in the experimental group had significantly lower scores on the pathway of hope subscales than those in the control group. CONCLUSIONS: A strengths-based perspective support group intervention designed specifically for women who left a violent intimate partner relationship significantly reduced the participants' level of depressive symptoms and improved the pathway component of hope. RELEVANCE TO CLINICAL PRACTICE: This research highlights the importance of nurses not only focused on problems but also on the psychological strengths in practice of abused women survivors.


Asunto(s)
Trastorno Depresivo/psicología , Violencia de Pareja/psicología , Adulto , Pueblo Asiatico , Mujeres Maltratadas/psicología , Trastorno Depresivo/enfermería , Femenino , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Grupos de Autoayuda , Encuestas y Cuestionarios , Taiwán , Salud de la Mujer
8.
AIDS Care ; 26(8): 996-1003, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24423628

RESUMEN

Few empirical studies have evaluated the mediating effects of quality of life (QoL) among people living with HIV/AIDS (PLWHA). The purposes of this study were to identify the predictors of QoL and to test the mediating effects of social support on depression and QoL among patients enrolled in an HIV case-management program in Taiwan. A cross-sectional, descriptive correlation design collected data from 108 HIV-infected individuals. Individuals were assessed using the Beck Depression Inventory II, the short version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF), and the Multidimensional Scale of Perceived Social Support between September 2007 and April 2010. After adjusting for sociodemographic characteristics (including age, gender, and mode of transmission) and clinical information (including CD4 count and time since diagnosis with HIV), the study findings showed that QoL was significantly and positively correlated with both social support and the initiation of highly active antiretroviral therapy (HAART), and was negatively correlated with depression and time since diagnosis with HIV. The strongest predictors for QoL were depression followed by the initiation of HAART and social support, with an R(2) of 0.40. Social support partially mediated the relationship between depression and QoL. Health professionals should enhance HIV-infected individuals' social support to alleviate the level of depression and further increase the QoL among PLWHA.


Asunto(s)
Depresión/epidemiología , Infecciones por VIH/psicología , Calidad de Vida , Apoyo Social , Adulto , Terapia Antirretroviral Altamente Activa/psicología , Estudios Transversales , Depresión/psicología , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estadística como Asunto , Taiwán/epidemiología , Adulto Joven
9.
J Transcult Nurs ; : 10436596241274353, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245932

RESUMEN

INTRODUCTION: The challenges faced by male migrant workers during the pandemic have not been fully understood. This study aimed to explore the experiences of male Indonesian migrant workers during the COVID-19 pandemic in Taiwan. METHODOLOGY: This study used an interpretive phenomenological design. Twenty male Indonesian migrant workers in southern Taiwan were individually interviewed. Data were analyzed using reflective thematic analysis. RESULTS: The migrant workers had conflicting emotions during the pandemic, faced challenges during self-quarantine, lived on board ships, and experienced restrictions on social and religious activities. The workers prioritized maintaining their health to ensure that they would not be easily infected while working. COVID-19 vaccines were made available to migrant workers in Taiwan. The workers had many hopes that they would achieve a better and more prosperous life by working in Taiwan than in their home country. DISCUSSION: Although the 3-year COVID-19 period was difficult for Indonesian migrant workers in Taiwan, Taiwan's policies provided hope for them to endure the pandemic. The results have implications for Taiwan's health care system, labor development, and transcultural health care.

10.
Nanoscale Adv ; 6(2): 524-533, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38235084

RESUMEN

Ferroptosis has attracted much attention for tumor treatment. It has been recently identified that castration-resistant prostate cancer (CRPC) is vulnerable to ferroptosis inducers. Notably, chemodynamic therapy (CDT), triggered by metal ions, could easily induce ferroptosis via a Fenton/Fenton-like reaction, but its efficiency was highly dependent on the intracellular H2O2 concentration, posing significant changes for its clinical translation. Herein, we attached glucose oxidase (GOx) onto the surface of manganese sulfide (MnS) and developed therapeutic nanocomposites (Lpo@MnS-GOx) after encapsulating with liposome. Upon internalization by cancer cells, the released GOx could transform glucose into gluconic acid (GA) and H2O2. Notably, the generated GA stimulates the degradation of MnS, followed by the promotion of the release of H2S and Mn2+, whereas the produced H2O2 can amplify the Fenton-like response initiated by Mn2+. The enhanced CDT combined with the gas therapy effect could simultaneously promote the accumulation of reactive oxygen species and finally induce ferroptosis and exhibit an excellent anti-tumor effect. Consequently, these Lpo@MnS-GOx NPs with enhanced ferroptosis-induced effect will find great potential for CRPC cancer treatment.

11.
Clin Nucl Med ; 49(1): e6-e7, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37976533

RESUMEN

ABSTRACT: A 37-year-old man was admitted to our hospital after experiencing syncope. An MRI of his head revealed multiple foci of abnormal signal, which could potentially be metastases. The patient then underwent a 68 Ga-FAPI-04 PET/MRI examination, which revealed multiple FAPI-avid foci in the brain. Upon analyzing the cerebrospinal fluid, it was found that the patient had a Staphylococcus aureus infection. The results suggest that 68 Ga-FAPI-04 PET has the potential to be a valuable tool in the visualization of intracranial infectious lesions.


Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Masculino , Humanos , Adulto , Infecciones Estafilocócicas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Radioisótopos de Galio , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18
12.
Int J Biol Macromol ; 278(Pt 2): 134711, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151847

RESUMEN

Pressure ulcer dressings with different functions can enhance wound healing ability to varying degrees; however, pressure ulcer dressings that integrate various functions and break the resistance of bacteria to traditional antibiotics have not been widely studied. We proposed a self-pumping/super-absorbent/transportable drug dressing (PLD-SLD), polycaprolactone (PCL)/sodium alginate (SA) was used to load platelet-derived growth factor (PDGF) and lidocaine hydrochloride (LID) by Janus electrospinning and self-assembly technology, and Ɛ-polylysine was used as a biological bacteriostatic agent to prepare a multi-layer dressing. SEM showed that the dressing had a fluffy structure. The dressing can pump the exudate to the SA layer away from the skin. The swelling ratio reached 1378.667 ± 44.752 %. Coagulate blood in 5 min. On the 8th day, the unclosed area rate of the PLD-SLD dressing group was 16.112 ± 0.088 % lower than that of the model group. Importantly, the dressing can induce the expression of CD31, VEGF, α-SMA, and reduce the expression of CD68, thereby giving priority to wound healing. There was no scar formation after healing. In this study, a new dressing preparation method was proposed for the problems of exudate management, infection control, pain relief and healing promotion of stage 3-4 pressure ulcer healing.


Asunto(s)
Alginatos , Vendajes , Poliésteres , Úlcera por Presión , Cicatrización de Heridas , Alginatos/química , Úlcera por Presión/tratamiento farmacológico , Úlcera por Presión/terapia , Poliésteres/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Ratas , Masculino , Lidocaína/farmacología , Lidocaína/química
13.
Life Sci ; 336: 122352, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38104863

RESUMEN

BACKGROUND: During aging, excessive ROS production in the kidneys leads to redox imbalance, which contributes to oxidative damage and impaired organ homeostasis. However, whether and how aging-related NOX4-Nrf2 redox imbalance increases susceptibility to cisplatin-induced acute kidney injury remain largely unknown. METHODS: In this study, we used cisplatin-challenged aging mouse models and senescent HK-2 cells to investigate the effects and mechanisms of aging on susceptibility to cisplatin-induced acute kidney injury. RESULTS: In vivo, we found that cisplatin stimulation caused more severe renal damage, oxidative stress, mitochondrial dysfunction and mitophagy impairment in aging mice than in young mice. Moreover, Nrf2 deficiency aggravated cisplatin-induced acute kidney injury by exacerbating NOX4-Nrf2 redox imbalance and defective mitophagy. In vitro experiments on D-gal-treated human renal tubular epithelial cells (HK-2) demonstrated that senescent renal epithelial cells exhibited increased susceptibility to cisplatin-induced apoptosis, NOX4-Nrf2 redox imbalance-mediated oxidative stress and defective mitophagy. Mechanistically, we found that knockdown of Nrf2 in HK2 cells resulted in increased ROS and aggravated mitophagy impairment, whereas these effects were reversed in NOX4-knockdown cells. CONCLUSION: The present study indicates that NOX4-Nrf2 redox imbalance is critical for mitophagy deficiency in aged renal tubular epithelial cells and is a therapeutic target for alleviating cisplatin-induced acute kidney injury in elderly patients.


Asunto(s)
Lesión Renal Aguda , Cisplatino , Humanos , Ratones , Animales , Anciano , Cisplatino/toxicidad , Cisplatino/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Mitofagia , Especies Reactivas de Oxígeno/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Envejecimiento , Riñón/metabolismo , Estrés Oxidativo , Oxidación-Reducción , NADPH Oxidasa 4/metabolismo
14.
Int J Biol Macromol ; 256(Pt 2): 128533, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38042313

RESUMEN

In this study, a multifunctional nanofiber dressing that can promote antibacterial, analgesic and healing was prepared by electrospinning technology. Hydrophobic polycaprolactone (PCL)/chitosan (CS)/lidocaine hydrochloride (LID) and epidermal growth factor (EGF) were used as scaffold materials and dissolved in trifluoroacetic acid to prepare spinning solution. The morphology of PCEL dressing was observed by scanning electron microscopy. The fiber structure was dense and the average diameter was 297.0 nm. The water absorption capacity test and water contact angle measurement showed that the fiber had good water absorption and hydrophilicity (1302 %, 139.258°). Drug release was 84 % within 60 h. In the results of antibacterial experiment, the dressing showed certain antibacterial properties. The results of cell experiments show that the dressing can promote cell proliferation. In addition, coagulation experiments showed that the dressing could quickly coagulate the blood within 4 min. In addition, PCEL dressing promoted collagen deposition and vascularization through animal models of pressure sores. Therefore, multifunctional dressing can be used as an ideal auxiliary means for the treatment of pressure sores, and it is a promising alternative to chronic wound healing.


Asunto(s)
Quitosano , Nanofibras , Úlcera por Presión , Animales , Quitosano/química , Lidocaína/farmacología , Lidocaína/uso terapéutico , Úlcera por Presión/tratamiento farmacológico , Nanofibras/química , Antibacterianos/química , Poliésteres/química , Agua/química
15.
Clin Transl Med ; 14(5): e1678, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38736108

RESUMEN

BACKGROUND: Cyclin-dependent kinase 12 (CDK12)-deficient prostate cancer defines a subtype of castration-resistant prostate cancer (CRPC) with a poor prognosis. Current therapy, including PARP inhibitors, shows minimal treatment efficacy for this subtype of CRPC, and the underlying mechanism remains elusive. METHODS: Based on bioinformatics analysis, we evaluated the relationship between CDK12 deficiency and prostate cancer patient's prognosis and treatment resistance. Furthermore, we used CRISPR-Cas9 technology and mass spectrometry-based metabolomic profiling to reveal the metabolic characteristics of CDK12-deficient CRPC. To elucidate the specific mechanisms of CDK12 deficiency-mediated CRPC metabolic reprogramming, we utilized cell RNA-seq profiling and other molecular biology techniques, including cellular reactive oxygen species probes, mitochondrial function assays, ChIP-qPCR and RNA stability analyses, to clarify the role of CDK12 in regulating mitochondrial function and its contribution to ferroptosis. Finally, through in vitro drug sensitivity testing and in vivo experiments in mice, we identified the therapeutic effects of the electron transport chain (ETC) inhibitor IACS-010759 on CDK12-deficient CRPC. RESULTS: CDK12-deficient prostate cancers reprogramme cellular energy metabolism to support their aggressive progression. In particular, CDK12 deficiency enhanced the mitochondrial respiratory chain for electronic transfer and ATP synthesis to create a ferroptosis potential in CRPC cells. However, CDK12 deficiency downregulated ACSL4 expression, which counteracts the lipid oxidation stress, leading to the escape of CRPC cells from ferroptosis. Furthermore, targeting the ETC substantially inhibited the proliferation of CDK12-deficient CRPC cells in vitro and in vivo, suggesting a potential new target for the therapy of CDK12-deficient prostate cancer. CONCLUSIONS: Our findings show that energy and lipid metabolism in CDK12-deficient CRPC work together to drive CRPC progression and provide a metabolic insight into the worse prognosis of CDK12-deficient prostate cancer patients. KEY POINTS: CDK12 deficiency promotes castration-resistant prostate cancer (CRPC) progression by reprogramming cellular metabolism. CDK12 deficiency in CRPC leads to a more active mitochondrial electron transport chain (ETC), ensuring efficient cell energy supply. CDK12 phosphorylates RNA Pol II to ensure the transcription of ACSL4 to regulate ferroptosis. Mitochondrial ETC inhibitors exhibit better selectivity for CDK12-deficient CRPC cells, offering a promising new therapeutic approach for this subtype of CRPC patients.


Asunto(s)
Quinasas Ciclina-Dependientes , Ferroptosis , Neoplasias de la Próstata Resistentes a la Castración , Animales , Humanos , Masculino , Ratones , Línea Celular Tumoral , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/genética , Progresión de la Enfermedad , Ferroptosis/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Oxadiazoles/farmacología , Piperidinas/farmacología
16.
Healthcare (Basel) ; 11(12)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37372788

RESUMEN

Long-acting antipsychotic injections require that psychiatric nurses choose the proper injection site and technique to avoid harming patients. This research conducted a mixed-method study to examine the long-acting injectable antipsychotic (LAI) knowledge, practice, and administrative barriers in a sample of 269 psychiatric nurses from 3 public psychiatric hospitals in Taiwan. Self-report questionnaires showed female nurses exhibiting higher scores and older nurses demonstrating more knowledge. The dorsogluteal (DG) site was the most widely used for injections, with 57.6% of nurses using the Z-track method. Qualitative data analysis was performed on 20 psychiatric nurses who chose the DG site as their preferred injection site. There were two key themes. The first was a gap between the nurses' knowledge of LAI administration and their actual practice. The second needed more confidence and training in using the ventrogluteal injection site. These results highlight the need for continued education and training to improve LAI practice among psychiatric nurses.

17.
Biomed Pharmacother ; 165: 115097, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37406514

RESUMEN

OBJECTIVE: Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on acetaminophen-induced hepatotoxicity remains unclear. METHODS: The hepatoprotective effects of xanthohumol were studied using APAP-induced HepG2 cells and acute liver injury of mouse, seperately. RESULTS: In vitro, xanthohumol inhibited H2O2- and acetaminophen-induced cytotoxicity and oxidative stress. Xanthohumol up-regulated the expression of Nrf2. Further mechanistic studies showed that xanthohumol triggered Nrf2 activation via the AMPK/Akt/GSK3ß pathway to exert a cytoprotective effect. In vivo, xanthohumol significantly ameliorated acetaminophen-induced mortality, the elevation of ALT and AST, GSH depletion, MDA formation and histopathological changes. Xanthohumol effectively suppressed the phosphorylation and mitochondrial translocation of JNK, mitochondrial translocation of Bax, the activation o cytochrome c, AIF secretion and Caspase-3. In vivo, xanthohumol increased Nrf2 nuclear transcription and AMPK, Akt and GSK3ß phosphorylation in vivo. In addition, whether xanthohumol protected against acetaminophen-induced liver injury in Nrf2 knockout mice has not been illustated. CONCLUSION: Thus, xanthohumol exerted a hepatoprotective effect by inhibiting oxidative stress and mitochondrial dysfunction through the AMPK/Akt/GSK3ß/Nrf2 antioxidant pathway.


Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Ratones , Acetaminofén/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Transducción de Señal , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo , Hígado , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo
18.
Heliyon ; 9(9): e19706, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809557

RESUMEN

The present study aimed to develop and psychometrically test a scale by using the Theory of Planned Behavior (TPB) comprising two types of measurement (direct and belief-based [indirect]) to assess bystander help-giving intention to victims of dating violence among youth. A two-phase, mixed-method design was adopted. The primary source of the samples was five universities, each in the northern, central, southern, eastern, and outer islands regions of Taiwan. Phase I involved developing an instrument based on the TPB (n = 10) and pilot testing (n = 220). Phase II conducted the psychometric evaluation (n = 622). The study used item analysis, explanatory factor analysis, confirmatory factor analysis, internal consistency, and cross-validation to examine the psychometric properties of the Dating Violence Bystander Help-giving Intention Questionnaire (DVBHIQ) with two types of measure (direct and belief-based). Explanatory factor analysis resulted in a four-factor solution (attitude/behavioral beliefs, subjective norms/normative beliefs, perceived behavioral control/control belief, and intention) of the direct and belief-based measures of the DVBHIQ, accounting for 72.67% and 76.62% of total variance respectively. Confirmatory factor analysis and cross-validation confirmed the proposed four-factor model and demonstrated good internal consistency reliability. The two types of DVBHIQ had good validity, reliability, and measurement invariance which may help address the core cognitive determinants for bystander help-giving intention. Healthcare providers (e.g., school nurses) could use the DVBHIQ to evaluate how bystander education programs affect youth and conduct related research in the future.

19.
Eur J Oncol Nurs ; 62: 102254, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36621263

RESUMEN

PURPOSE: This study aimed to investigate the correlations and identify the relationships between the resilience, perception of illness and body image of women with breast cancer in the 5-year-or-above survivorship. METHODS: We used convenient sampling to recruit from an outpatient department 106 women with breast cancer. The inclusion criteria were participants aged >20 years currently in a stable condition and were able to understand the Chinese language. Those women with mental health illness were excluded. All participants completed questionnaires on the following: demographic information, revision of illness perception (IPQ-R), body image scale (BIS), Eysenck personality questionnaire (EPQ), and resilience scale (RS). We conducted the structural equation modeling (SEM) to explore the factor structure. RESULTS: SEM results showed a good fit to the data (comparative fit index = 0.97, Tucker-Lewis index = 0.94). Findings F indicated the existence of significant relationships between resilience and either illness perception or body image. Personality had a direct association with illness perception (ß = 0.73, P < 0.05). Body image had an indirect effect on the relationship between resilience and illness perception (coefficient = -2.52; 95% bootstrapping CI = -31.36, -0.62). CONCLUSIONS: Results indicated that illness perception is a crucial predictor for better resilience as mediated through body image. To provide adequate information to women with breast cancer can improve their perception of breast cancer more positively. Hence, their body image and their way of coping with survival life turn better.


Asunto(s)
Imagen Corporal , Neoplasias de la Mama , Humanos , Femenino , Imagen Corporal/psicología , Neoplasias de la Mama/psicología , Adaptación Psicológica , Encuestas y Cuestionarios , Salud Mental
20.
Biology (Basel) ; 12(5)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37237481

RESUMEN

To investigate a safe and effective approach for enhancing the in vivo expression of recombinant genes and improving the systemic immunity of animals against infectious diseases, we employed the interleukin-7 (IL-7) gene from Tibetan pigs to construct a recombinant eukaryotic plasmid (VRTPIL-7). We first examined VRTPIL-7's bioactivity on porcine lymphocytes in vitro and then encapsulated it with polyethylenimine (PEI), chitosan copolymer (CS), PEG-modified galactosylated chitosan (CS-PEG-GAL) and methoxy poly (ethylene glycol) (PEG) and PEI-modified CS (CS-PEG-PEI) nanoparticles using the ionotropic gelation technique. Next, we intramuscularly or intraperitoneally injected mice with various nanoparticles containing VRTPIL-7 to evaluate their immunoregulatory effects in vivo. We observed a significant increase in neutralizing antibodies and specific IgG levels in response to the rabies vaccine in the treated mice compared to the controls. Treated mice also exhibited increased leukocytes, CD8+ and CD4+ T lymphocytes, and elevated mRNA levels of toll-like receptors (TLR1/4/6/9), IL-1, IL-2, IL-4, IL-6, IL-7, IL-23, and transforming growth factor-beta (TGF-ß). Notably, the recombinant IL-7 gene encapsulated in CS-PEG-PEI induced the highest levels of immunoglobulins, CD4+ and CD8+ T cells, TLRs, and cytokines in the mice's blood, suggesting that chitosan-PEG-PEI may be a promising carrier for in vivo IL-7 gene expression and enhanced innate and adaptive immunity for the prevention of animal diseases.

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