In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or ...bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.
Aims
This study examines how career barriers and supports (i.e., perceived discrimination, lack of advancement, human capital, and social capital) impact affective, normative, and continuance aspects ...of professional commitment and thus nurses’ professional turnover intention.
Background
Professional commitment is known to influence professional turnover intention. However, little is known about how career barriers and supports contribute to professional commitment and reduce professional turnover intention.
Methods
This study adopted a cross‐sectional design and a survey to collect representative data in a major hospital in northern Taiwan. We used proportionate random sampling to ensure sample representativeness and obtained 524 responses.
Results
Perceived discrimination and lack of advancement were negatively related to affective professional commitment. Human capital was positively related to affective, normative, and continuance professional commitment. Social capital was positively related to normative professional commitment. All aspects of professional commitment were negatively related to professional turnover intention.
Conclusion
Career barriers and supports have an important influence on professional commitment. Reduced barriers and enhanced support may therefore help reduce nurses’ professional turnover intentions.
Implications for Nursing Management.
Nursing managers could aim to lessen career barriers while increasing career support for nurses, helping strengthen nurses’ professional commitment and retention.
Over the past decades, promising therapies targeting different signaling pathways have emerged. Among these pathways, apoptosis has been well investigated and targeted to design diverse ...chemotherapies. However, some patients are chemoresistant to these therapies due to compromised apoptotic cell death. Hence, exploring alternative treatments aimed at different mechanisms of cell death seems to be a potential strategy for bypassing impaired apoptotic cell death. Emerging evidence has shown that necroptosis, a caspase-independent form of cell death with features between apoptosis and necrosis, can overcome the predicament of drug resistance. Furthermore, previous studies have also indicated that there is a close correlation between necroptosis and reactive oxygen species (ROS); both necroptosis and ROS play significant roles both under human physiological conditions such as the regulation of inflammation and in cancer biology. Several small molecules used in experiments and clinical practice eliminate cancer cells via the modulation of ROS and necroptosis. The molecular mechanisms of these promising therapies are discussed in detail in this review.
Background
Social cognitive career theory (SCCT) can explain the mechanism underlying the formulation of nurse turnover intention. However, little is known about the role of professional commitment ...in such a mechanism.
Aims
The aim of this study was to explore how elements of SCCT have an impact on the three aspects of professional commitment and thus nurses’ intention to leave the profession.
Design
This study used surveys to collect two‐wave data.
Methods
The participants were sampled in all available units of a major medical centre in 2017. By using proportionate random sampling methods, we successfully followed up a representative sample of 524 full‐time nurses. Most participants (98.1%) were female. Items came from Cunningham et al.'s Self‐Efficacy Scale, Outcome Expectations Scale, Human Capital Scale and Vocational Interest Scale; Meyer et al.'s Professional Commitment Scale; and Teng et al.'s Turnover Intention Scale. Structural equation modelling was used to test the hypotheses.
Results
Self‐efficacy was positively related to outcome expectation. Outcome expectation was positively related to career interest. Career interest was positively related to affective professional commitment. Human capital was positively related to normative professional commitment. Affective professional commitment was positively related to intention to improve professional capabilities, which was further negatively related to intention to leave the profession.
Conclusion
Aspects of professional commitment are important process variables in the impact of self‐efficacy and outcome expectation on nurses’ turnover intention.
背景
社会认知职业理论(SCCT)可以阐释护士离职意愿形成的机制。然而,对专业承诺在此类机制中发挥的作用知之甚少。
目的
本研究旨在探讨社会认知职业理论中的因素如何对专业承诺的三个方面以及护士离职意愿产生影响。
设计
本研究通过调查收集两波数据。
方法
对2017年某大型医疗中心所有可用受试者单位进行抽样调查。采用按比例随机抽样方法,我们成功地获得了524名全职护士的代表性样本。大多数参与者(98.1%)为女性。样本项目来自Cunningham等人的自我效能量表、成果预期量表、人力资本量表和职业兴趣量表;Meyer等人的专业承诺量表;Teng等人的离职意向量表,并采用结构方程模型对假设进行验证。
结果
自我效能感与结果预期呈正相关。结果预期与职业兴趣呈正相关。职业兴趣与情感专业承诺呈正相关。人力资本与规范的专业承诺呈正相关。情感专业承诺与提高职业能力的意愿呈正相关,与离职意愿呈负相关。
结论
专业承诺方面是影响护士自我效能感和结果预期对护士离职意愿影响的重要过程变量。
Aims
To examine the impact of burnout on self‐efficacy, outcome expectations, career interest and on nurses’ intentions to leave the profession and to leave the organization.
Background
Burnout is ...associated with nurse turnover. Research clarifying the underlying mechanism may provide a novel means to mitigate the impact of burnout on nurse turnover.
Design
This study uses a cross‐sectional design and proportionate stratified sampling.
Methods
Data were collected from a sample of nurses in one medical centre in northern Taiwan during February ‐ March 2017. This study included nurses employed full‐time at the medical centre. Burnout was measured using Maslach Burnout Inventory—Human Service Survey. Self‐efficacy, outcome expectations and career interest were measured using the scale of Cunningham et al. Intentions to leave were measured using the scales of Teng et al. Structural equation modelling was used to assess the proposed framework.
Results
Burnout was negatively related to self‐efficacy and outcome expectations. Self‐efficacy was positively related to outcome expectations. Outcome expectations were also positively related to career interest. However, self‐efficacy was not related to career interest. Career interest was negatively related to the intention to leave the organization, which was further related to the intention to leave the profession. The model fitted the data acceptably.
Conclusions
When nurses leave the profession, patient outcomes may be affected. Policy makers should evaluate whether the healthcare system can instil expectations for satisfaction, power and adequate compensation in the profession and thus retain nurses.
目标
研究护士倦怠对自我效能、结果期望、职业兴趣及离职和转行意图的影响。
背景
职业倦怠与护士流动有关。对潜在机制进行说明的研究可以提供一种新的方法来缓和职业倦怠对护士流动的影响。
设计
本研究采用了横断面设计和比例分层抽样方法。
方法
这些数据是在2017年2月至3月期间,在台湾北部的一个医疗中心的护士样本中收集的。这项研究包括该中心的全职护士。使用Maslach职业倦怠量表(服务行业版)来衡量职业倦怠。使用坎宁安等人的标准来衡量自我效能、结果期望和职业兴趣。使用Teng等人的标准来衡量离职意图。同时,采用结构方程建模来评估所提出的框架。
结果
职业倦怠与自我效能和结果期望呈负相关。自我效能与结果期望呈正相关。结果期望也与职业兴趣呈正相关。然而,自我效能与职业兴趣无关。职业兴趣与转行意向呈负相关,这与离职意图有进一步的联系。该模型符合数据可接受性要求。
结论
当护士离职时,患者的情况可能会受到影响。政策制定者应该评估医疗保健系统是否能在职业中满足护士对满意度和权力及适当补偿的期望,从而留住护士。
Aims and objectives
This study examines the impacts of mentor–mentee rapport on willingness to mentor/be mentored, self‐efficacy, outcome expectations, career interest and subsequently on nurses’ ...professional turnover intention.
Background
Workplace relationships, whether positive or negative, influence nurse turnover within an organisation. Yet little is known about the effects of mentoring on nurses’ intentions to leave the nursing profession.
Design
A cross‐sectional, survey‐based research design was used to collect data from a large medical centre in Northern Taiwan.
Methods
Study concepts were measured using scales from social capital theory (SCT), social cognitive career theory (SCCT) and the nursing literature. Partial least square structural equation modelling was used to test all study hypotheses. The STROBE statement was chosen as the EQUATOR checklist.
Results
For mentors, rapport was positively related to willingness to mentor, which was positively related to outcome expectations, and further, positively related to career interest and negatively related to professional turnover intention. For mentees, rapport was positively related to willingness to be mentored, which was positively related to self‐efficacy, outcome expectations and ultimately to career interest. Career interest was negatively related to professional turnover intentions.
Conclusions
Rapport between mentors and mentees may be an important means to retain nurses in the profession.
Relevance to clinical practice
Managers should consider taking steps to enhance rapport between mentors and mentees. In doing so, managers improve nurse retention, a critical component of providing high‐quality patient care.
Hepatocellular carcinoma (HCC) is a leading cause of death, resulting in over 700 thousand deaths annually worldwide. Chemotherapy is the primary therapeutic strategy for patients with late-stage ...HCC. Heteronemin is a marine natural product isolated from Hippospongia sp. that has been found to protect against carcinogenesis in cholangiocarcinoma, prostate cancer, and acute myeloid leukemia. In this study, heteronemin was found to inhibit the proliferation of the HCC cell lines HA22T and HA59T and induce apoptosis via the caspase pathway. Heteronemin treatment also induced the formation of reactive oxygen species (ROS), which are associated with heteronemin-induced cell death, and to trigger ROS removal by mitochondrial SOD2 rather than cytosolic SOD1. The mitogen-activated protein kinase (MAPK) signaling pathway was associated with ROS-induced cell death, and heteronemin downregulated the expression of ERK, a MAPK that is associated with cell proliferation. Inhibitors of JNK and p38, which are MAPKs associated with apoptosis, restored heteronemin-induced cell death. In addition, heteronemin treatment reduced the expression of GPX4, a protein that inhibits ferroptosis, which is a novel form of nonapoptotic programmed cell death. Ferroptosis inhibitor treatment also restored heteronemin-induced cell death. Thus, with appropriate structural modification, heteronemin can act as a potent therapeutic against HCC.
Induction of apoptosis by endoplasmic reticulum (ER) stress is implicated as the major factor in the development of multiple diseases. ER stress also appears to be a potentially useful major response ...to many chemotherapeutic drugs and environmental chemical compounds. A previous study has indicated that one major apoptotic regulator, p53, is significantly increased in response to ER stress, and participates in ER stress-induced apoptosis. However, the regulators of p53 expression during ER stress are still not fully understood.
In this report, we demonstrate that induction of p53 expression is mediated through NF-κB signaling pathways during ER stress in MCF-7 cells. Tunicamycin or brefeldin A, two ER stress inducers, increased p53 expression in MCF-7 and Hela cells. We found p53 nuclear localization, activity, and phosphorylation at serine 15 on p53 increased during ER stress. Nuclear translocation of NF-κB and activity of NF-κB were also observed during ER stress. ER stress-induced p53 expression was significantly inhibited by coincubation with the NF-κB inhibitor, Bay 11-7082 and downregulation of NF-κB p65 expression. The role of p53 in mediating Brefeldin A-induced apoptosis was also investigated. Induction of p53 expression by Brefeldin A was correlated to Brefeldin A-induced apoptosis. Furthermore, downregulation of p53 expression by p53 siRNA significantly reduced Brefeldin A-induced apoptosis in MCF-7 cells.
Taken together, NF-κB activation and induction of p53 expression is essential for ER stress-induced cell death which is important for therapeutic effects of clinical cancer drugs. Our results may provide insight into the mechanism of cancer chemotherapy efficacy that is associated with induction of ER stress.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the leading cause of cancer-related mortality worldwide. Chemotherapy is the major treatment modality for advanced or ...unresectable HCC; unfortunately, chemoresistance results in a poor prognosis for HCC patients. Exogenous ceramide, a sphingolipid, has been well documented to exert anticancer effects. However, recent reports suggest that sphingolipid metabolism in ceramide-resistant cancer cells favors the conversion of exogenous ceramides to prosurvival sphingolipids, conferring ceramide resistance to cancer cells. However, the mechanism underlying ceramide resistance remains unclear. We previously demonstrated that diTFPP, a novel phenoxyphenol compound, enhances the anti-HCC effect of C2-ceramide. Here, we further clarified that treatment with C2-ceramide alone increases the protein level of CERS2, which modulates sphingolipid metabolism to favor the conversion of C2-ceramide to prosurvival sphingolipids in HCC cells, thus activating the unfolded protein response (UPR), which further initiates autophagy and the reversible senescence-like phenotype (SLP), ultimately contributing to C2-ceramide resistance in these cells. However, cotreatment with diTFPP and ceramide downregulated the protein level of CERS2 and increased oxidative and endoplasmic reticulum (ER) stress. Furthermore, insufficient LAMP2 glycosylation induced by diTFPP/ceramide cotreatment may cause the failure of autophagosome–lysosome fusion, eventually lowering the threshold for triggering cell death in response to C2-ceramide. Our study may shed light on the mechanism of ceramide resistance and help in the development of adjuvants for ceramide-based cancer therapeutics.
Etoposide (ETO) has been used in treating adrenocortical tumor (ACT) cells. Our previous study showed that ETO inhibits ACT cell growth. In the present study, we show that ETO treatment at IC50 (10 ...μM) inhibited ACT cell growth by inducing cellular senescence rather than apoptosis. Several markers of cellular senescence, including enlarged nuclei, activated senescence-associated β-galactosidase activity, elevated levels of p53 and p21, and down-regulation of Lamin B1, were observed. We further found that ETO induced multiple centrosomes. The inhibition of multiple centrosomes accomplished by treating cells with either roscovitine or centrinone or through the overexpression of NR5A1/SF-1 alleviated ETO-induced senescence, suggesting that ETO triggered senescence via multiple centrosomes. Primary cilia also played a role in ETO-induced senescence. In the mechanism, DNA-PK-Chk2 signaling was activated by ETO treatment; inhibition of this signaling cascade alleviated multiple ETO-induced centrosomes and primary cilia followed by reducing cellular senescence. In addition to DNA damage signaling, autophagy was also triggered by ETO treatment for centrosomal events and senescence. Importantly, the inactivation of DNA-PK-Chk2 signaling reduced ETO-triggered autophagy; however, the inhibition of autophagy did not affect DNA-PK-Chk2 activation. Thus, ETO activated the DNA-PK-Chk2 cascade to facilitate autophagy. The activated autophagy further induced multiple centrosomes and primary cilia followed by triggering senescence.
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