bluuebunny/crossref_metadata_2025_split huggingface dataset:
E2F6/KDM5C promotes SF3A3 expression and bladder cancer progression through a specific hypomethylated DNA promoter
Authors: Liu Kai-Long , Yin Yue-Wei , Lu Bao-Sai , Niu Ya-Lin , Wang Dan-Dan , Shi Bei , Zhang Hong , Guo Ping-Ying , Yang Zhan , Li Wei 
Published: March 2022

Abstract
Background
Abnormal expression of splicing factor 3A subunit 3 (SF3A3), a component of the spliceosome, has been confirmed to be related to the occurrence and development of various cancers. However, the expression and function of SF3A3 in bladder cancer (BC) remains unclear.

Methods
The SF3A3 mRNA and protein level were measured in clinical samples and cell lines by quantitative real-time PCR, Western blot and immunofluorescence staining. Evaluate the clinical correlation between SF3A3 expression and clinicopathological characteristics through statistical analysis in BC patients. The function of SF3A3 in BC cells was determined in vitro using MTT and colony analysis. Co-immunoprecipitation (CoIP) assay was used to detected E2F6 and KDM5C interaction. Luciferase reporter and chromatin immunoprecipitation (ChIP) were used to examine the relationship between E2F6/KDM5C and SF3A3 expression.

Results
In the present study, we demonstrated that expression of SF3A3 was elevated in BC tissue compared to the normal bladder tissue. Importantly, the upregulation of SF3A3 in patients was correlated with poor prognosis. Additionally, overexpression of SF3A3 promoted while depletion of SF3A3 reduced the growth of BC cells in vivo and in vitro. Data from the TCGA database and clinical samples revealed that hypomethylation of the DNA promoter leads to high expression of SF3A3 in BC tissue. We found that upregulation of lysine-specific demethylase 5C (KDM5C) promotes SF3A3 expression via hypomethylation of the DNA promoter. The transcription factor E2F6 interacts with KDM5C, recruits KDM5C to the SF3A3 promoter, and demethylates the GpC island of H3K4me2, leading to high SF3A3 expression and BC progression.

Conclusions
The results demonstrated that depletion of the KDM5C/SF3A3 prevents the growth of BC in vivo and in vitro. The E2F6/KDM5C/SF3A3 pathway may be a potential therapeutic target for BC treatment.
The role of Th17 cells in the pathogenesis and treatment of breast cancer
Authors: Karpisheh Vahid , Ahmadi Majid , Abbaszadeh-Goudarzi Kazem , Mohammadpour Saray Mehran , Barshidi Asal , Mohammadi Hamed , Yousefi Mehdi , Jadidi-Niaragh Farhad 
Published: March 2022

AbstractBreast cancer is a severe problem worldwide due to an increase in mortality and prevalence among women. Despite early diagnostic procedures as well as advanced therapies, more investigation is required to find new treatment targets. Various factors and mechanisms, such as inflammatory conditions, can play a crucial role in cancer progression. Among them, Th17 cells are identified as effective CD4+ T cells that play an essential role in autoimmune diseases and inflammation which may be associated with anti-tumor responses. In addition, Th17 cells are one of the main factors involved in cancer, especially breast cancer via the inflammatory process. In tumor immunity, the exact mechanism of Th17 cells is not entirely understood and seems to have a dual function in tumor development. Various studies have reported that cytokines secreted by Th17 cells are in close relation to cancer stem cells and tumor microenvironment. Therefore, they play a critical role in the growth, proliferation, and invasion of tumor cells. On the other hand, most studies have reported that T cells suppress the growth of tumor cells by the induction of immune responses. In patients with breast cancer compared to normal individuals, various studies have been reported that the Th17 population dramatically increases in peripheral blood which results in cancer progression. It seems that Th17 cells by creating inflammatory conditions through the secretion of cytokines, including IL-22, IL-17, TNF-α, IL-21, and IL-6, can significantly enhance breast cancer progression. Therefore, to identify the mechanisms and factors involved in the activation and development of Th17 cells, they can provide an essential role in preventing breast cancer progression. In the present review, the role of Th17 cells in breast cancer progression and its therapeutic potential was investigated.
The importance of miRNA-630 in human diseases with an especial focus on cancers
Authors: Kadkhoda Sepideh , Ghafouri-Fard Soudeh 
Published: March 2022

AbstractmiR-630 is encoded by MIR630 gene (NC_000015.10) on 15q24.1. This miRNA is mostly associated with cytokine signaling in immune system. Several neoplastic as well as non-neoplastic conditions have been linked with dysregulation of miR-630. It is an oncogenic miRNA in renal cell carcinoma, multiple myeloma, colorectal cancer, acute lymphoblastic leukemia, ovarian cancer and prostate cancer. On the other hand, it is a putative tumor suppressor miRNA in lung, cervical, breast, thyroid and esophageal tissues. In a number of other tissues, data regarding the role of miR-630 in the carcinogenesis is conflicting. Expression levels of miR-630 can be used as markers for prediction of cancer course. Moreover, miR-630 can influence response to chemoradiotherapy. This miRNA is also involved in the pathoetiology of IgA nephropathy, obstructive sleep apnea, age-related nuclear cataract and vitiligo. In the present review, we discuss the role of miR-630 in these conditions.
DAB2IP predicts treatment response and prognosis of ESCC patients and modulates its radiosensitivity through enhancing IR-induced activation of the ASK1-JNK pathway
Authors: Tong Zhuting , Fang Weiyang , Xu Meng , Xia YeYe , Wang Rui , Li Yue , Zha Tianqi , Xiao Liang , Pan Shuhao , Chai Huiping , Zhao Lei , Wang Hao , Pan Huaguang , Chen Xiangcun 
Published: March 2022

Abstract
Background
Disabled homolog 2 interacting protein (DAB2IP) plays a tumor-suppressive role in several types of human cancers. However, the molecular status and function of the DAB2IP gene in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy is rarely reported.

Methods
We examined the expression dynamics of DAB2IP by immunohistochemistry (IHC) in 140 ESCC patients treated with definitive chemoradiotherapy. A series of in vivo and in vitro experiments were performed to elucidate the effect of DAB2IP on the chemoradiotherapy (CRT) response and its underlying mechanisms in ESCC.

Results
Decreased expression of DAB2IP in ESCCs correlated positively with ESCC resistance to CRT and was a strong and independent predictor for short disease-specific survival (DSS) of ESCC patients. Furthermore, the therapeutic sensitivity of CRT was substantially increased by ectopic overexpression of DAB2IP in ESCC cells. In addition, knockdown of DAB2IP dramatically enhanced resistance to CRT in ESCC. Finally, we demonstrated that DAB2IP regulates ESCC cell radiosensitivity through enhancing ionizing radiation (IR)-induced activation of the ASK1-JNK signaling pathway.

Conclusions
Our data highlight the molecular etiology and clinical significance of DAB2IP in ESCC, which may represent a new therapeutic strategy to improve therapy and survival for ESCC patients.
Continuous ZnO nanoparticle exposure induces melanoma-like skin lesions in epidermal barrier dysfunction model mice through anti-apoptotic effects mediated by the oxidative stress–activated NF-κB pathway
Authors: Wang Ping , Hu Guodong , Zhao Wen , Du Juan , You Menghan , Xv Mengying , Yang Hong , Zhang Min , Yan Fang , Huang Mianbo , Wang Xueer , Zhang Lin , Chen Yinghua 
Published: March 2022

Abstract
Background
Increasing interest in the hazardous properties of zinc oxide nanoparticles (ZnO NPs), commonly used as ultraviolet filters in sunscreen, has driven efforts to study the percutaneous application of ZnO NPs to diseased skin; however, in-depth studies of toxic effects on melanocytes under conditions of epidermal barrier dysfunction remain lacking.

Methods
Epidermal barrier dysfunction model mice were continuously exposed to a ZnO NP-containing suspension for 14 and 49 consecutive days in vivo. Melanoma-like change and molecular mechanisms were also verified in human epidermal melanocytes treated with 5.0 µg/ml ZnO NPs for 72 h in vitro.

Results
ZnO NP application for 14 and 49 consecutive days induced melanoma-like skin lesions, supported by pigmented appearance, markedly increased number of melanocytes in the epidermis and dermis, increased cells with irregular nuclei in the epidermis, recruited dendritic cells in the dermis and dysregulated expression of melanoma-associated gene Fkbp51, Trim63 and Tsp 1. ZnO NPs increased oxidative injury, inhibited apoptosis, and increased nuclear factor kappa B (NF-κB) p65 and Bcl-2 expression in melanocytes of skin with epidermal barrier dysfunction after continuously treated for 14 and 49 days. Exposure to 5.0 µg/ml ZnO NPs for 72 h increased cell viability, decreased apoptosis, and increased Fkbp51 expression in melanocytes, consistent with histological observations in vivo. The oxidative stress–mediated mechanism underlying the induction of anti-apoptotic effects was verified using the reactive oxygen species scavenger N-acetylcysteine.

Conclusions
The entry of ZnO NPs into the stratum basale of skin with epidermal barrier dysfunction resulted in melanoma-like skin lesions and an anti-apoptotic effect induced by oxidative stress, activating the NF-κB pathway in melanocytes.

Graphical Abstract
A CFH peptide-decorated liposomal oxymatrine inactivates cancer-associated fibroblasts of hepatocellular carcinoma through epithelial–mesenchymal transition reversion
Authors: Guo Jian , Zeng Huating , Shi Xinmeng , Han Tao , Liu Yimin , Liu Yuping , Liu Congyan , Qu Ding , Chen Yan 
Published: March 2022

AbstractCancer-associated fibroblasts (CAFs) deteriorate tumor microenvironment (TME) and hinder intra-tumoral drug delivery. Direct depleting CAFs exists unpredictable risks of tumor metastasis. Epithelial–mesenchymal transition (EMT) is a critical process of CAFs converted from hepatic stellate cells during hepatocellular tumorigenesis; however, until now the feasibility of reversing EMT to battle hepatocellular carcinoma has not been comprehensively explored. In this study, we report a CFH peptide (CFHKHKSPALSPVGGG)-decorated liposomal oxymatrine (CFH/OM-L) with a high affinity to Tenascin-C for targeted inactivating CAFs through reversing EMT, which is verified by the upregulation of E-cadherin and downregulation of vimentin, N-cadherin, and snail protein in vivo and in vitro. After the combination with icaritin-loaded lipid complex, CFH/OM-L obviously boosts the comprehensive anticancer efficacy in both 3D tumor spheroids and stromal-rich tumor xenograft nude mouse models. The combinational therapy not only effectively reversed the in vivo EMT process but also significantly lowered the collagen, creating favorable conditions for deep penetration of nanoparticles. More importantly, CFH/OM-L does not kill but inactivates CAFs, resulting in not only a low risk of tumor metastasis but also a reprogramming TME, such as M1 tumor-associated macrophages polarization and natural killer cells activation. Such strategy paves a moderate way to remold TME without depleting CAFs and provides a powerful tool to design strategies of combinational hepatocellular carcinoma therapy.
Graphical Abstract
Exposure to two-dimensional ultrathin Ti3C2 (MXene) nanosheets during early pregnancy impairs neurodevelopment of offspring in mice
Authors: Wen Yixian , Hu Le , Li Jian , Geng Yanqing , Yang Yang , Wang Jing , Chen Xuemei , Yu Liliang , Tang Hongyu , Han Tingli , Yang Yongxiu , Liu Xueqing 
Published: March 2022

Abstract
Background
Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have been extensively explored for various biomedical applications. However, safety issues and the effects of Ti3C2 on human health remain poorly understood.

Results
To explore the influence on foetal or offspring after exposure to Ti3C2 nanosheets, we established a mouse model exposed to different doses of Ti3C2 nanosheets during early pregnancy in this study. We found that Ti3C2 nanosheets had negligible effect on the reproductive ability of maternal mice, including average pregnancy days, number of new-borns, and neonatal weight, etc. Unexpectedly, abnormal neurobehavior and pathological changes in the cerebral hippocampus and cortex in adult offspring were observed following Ti3C2 nanosheet treatment. In further studies, it was found that Ti3C2 exposure led to developmental and functional defects in the placenta, including reduced area of labyrinth, disordered secretion of placental hormones, and metabolic function derailment. The long-chain unsaturated fatty acids were significantly higher in the placenta after Ti3C2 exposure, especially docosahexaenoic acid (DHA) and linoleic acid. The metabolic pathway analysis showed that biosynthesis of unsaturated fatty acids was upregulated while linoleic acid metabolism was downregulated.

Conclusions
These developmental and functional defects, particularly metabolic function derailment in placenta may be the cause for the neuropathology in the offspring. This is the first report about the effects of Ti3C2 nanosheet exposure on pregnancy and offspring. The data provides a better understanding of Ti3C2 nanosheets safety. It is suggested that future studies should pay more attention to the long-term effects of nanomaterials exposure, including the health of offspring in adulthood, rather than only focus on short-term effects, such as pregnancy outcomes. Metabolomics could provide clues for finding the prevention targets of the biological negative effect of Ti3C2 nanosheets.

Graphical Abstract
A novel antibacterial and antifouling nanocomposite coated endotracheal tube to prevent ventilator-associated pneumonia
Authors: Wang Yue , Cai Bingyue , Ni Dalong , Sun Yu , Wang Gang , Jiang Hong 
Published: March 2022

Abstract
Background
The endotracheal tube (ETT) is an essential medical device to secure the airway patency in patients undergoing mechanical ventilation or general anesthesia. However, long-term intubation eventually leads to complete occlusion, ETTs potentiate biofilm-related infections, such as ventilator-associated pneumonia. ETTs are mainly composed of medical polyvinyl chloride (PVC), which adheres to microorganisms to form biofilms. Thus, a simple and efficient method was developed to fabricate CS-AgNPs@PAAm-Gelatin nanocomposite coating to achieve dual antibacterial and antifouling effects.

Results
The PAAm-Gelatin (PAAm = polyacrylamide) molecular chain gel has an interpenetrating network with a good hydrophilicity and formed strong covalent bonds with PVC-ETTs, wherein silver nanoparticles were used as antibacterial agents. The CS-AgNPs@PAAm-Gelatin coating showed great resistance and antibacterial effects against Staphylococcus aureus and Pseudomonas aeruginosa. Its antifouling ability was tested using cell, protein, and platelet adhesion assays. Additionally, both properties were comprehensively evaluated using an artificial broncho-lung model in vitro and a porcine mechanical ventilation model in vivo. These remarkable results were further confirmed that the CS-AgNPs@PAAm-Gelatin coating exhibited an excellent antibacterial capacity, an excellent stain resistance, and a good biocompatibility.

Conclusions
The CS-AgNPs@PAAm-Gelatin nanocomposite coating effectively prevents the occlusion and biofilm-related infection of PVC-ETTs by enhancing the antibacterial and antifouling properties, and so has great potential for future clinical applications.

Graphical Abstract
Psychometric properties of the Depression Stigma Scale in the Portuguese population and its association with gender and depressive symptomatology
Authors: Conceição Virgínia , Rothes Inês , Severo Milton , Griffiths Kathleen , Hegerl Ulrich , Gusmão Ricardo 
Published: March 2022

Abstract
Background
Stigma is one of the most significant constraints on people living with depression. There is a lack of validated scales in Portugal to measure depression stigma; therefore, the Depression Stigma Scale (DSS) is essential to the depression stigma research in Portugal.

Methods
We developed the adaptation process with the ITC Guidelines for Translation and Adapting Tests taken into consideration. We collected the sample as part of the OSPI program—Optimizing suicide prevention programs and their implementation in Europe, specifically within the application in Portugal, and included 1693 participants. Floor-ceiling effects and response ranges were analyzed, and we calculated Cronbach alphas, and Confirmatory Analysis. Validity evidence was tested with two well-documented hypotheses, using data on gender and depression symptoms.

Results
The sample was well comparable with the general Portuguese population, indicating its representativeness. We identified a three-factor structure in each subscale (personal and perceived stigma): weak-not-sick, discrimination, and dangerous/unpredictable, with good model fit results. The Cronbach's alphas were satisfactory, and validity was confirmed.

Conclusions
This study established the validity and demonstrated good psychometric properties of the DSS in the Portuguese population. The validation of the DSS can be beneficial in exploring stigma predictors and evaluating the effectiveness of stigma reduction interventions.
Psychometric assessment of scales for measuring loneliness and social isolation: an analysis of the household, income and labour dynamics in Australia (HILDA) survey
Authors: Manera Karine E. , Smith Ben J. , Owen Katherine B. , Phongsavan Philayrath , Lim Michelle H. 
Published: March 2022

Abstract
Background
Loneliness and social isolation are increasingly recognised as global public health threats, meaning that reliable and valid measures are needed to monitor these conditions at a population level. We aimed to determine if robust and practical scales could be derived for conditions such as loneliness and social isolation using items from a national survey.

Methods
We conducted psychometric analyses of ten items in two waves of the Household, Income and Labour Dynamics in Australia Survey, which included over 15,000 participants. We used the Hull method, exploratory structural equation modelling, and multidimensional item response theory analysis in a calibration sample to determine the number of factors and items within each factor. We cross-validated the factor structure using confirmatory factor analysis in a validation sample. We assessed construct validity by comparing the resulting sub-scales with measures for psychological distress and mental well-being.

Results
Calibration and cross-validation consistently revealed a three-factor model, with sub-scales reflecting constructs of loneliness and social isolation. Sub-scales showed high reliability and measurement invariance across waves, gender, and age. Construct validity was supported by significant correlations between the sub-scales and measures of psychological distress and mental health. Individuals who met threshold criteria for loneliness and social isolation had consistently greater odds of being psychologically distressed and having poor mental health than those who did not.

Conclusions
These derived scales provide robust and practical measures of loneliness and social isolation for population-based research.
Inequal distribution of nursing personnel: a subnational analysis of the distribution of nurses across 58 countries
Authors: Boniol Mathieu , McCarthy Carey , Lawani Deen , Guillot Gilles , McIsaac Michelle , Diallo Khassoum 
Published: March 2022

Abstract
Background
Nursing personnel are critical for enabling access to health service in primary health care. However, the State of the World’s Nursing 2020 report showed important inequalities in nurse availability between countries.

Methods
The purpose of this study/analysis was to describe the differences in nurse-to-population density in 58 countries from six regional areas and the relationship between differences in access to nurses and other indicators of health equity.

Results
All countries and income groups showed subnational inequalities in the distribution of nursing personnel with Gini coefficients ranging from 1 to 39. The latter indicated situation such as 13% of the population having access to 45% of nurses in a country. The average max-to-min ratio was on average of 11-fold. In our sample, the African region had the highest level of subnational inequalities with the average Gini coefficient of 19.6. The European Region had the lowest level of within-country inequalities with the average Gini coefficient being 5.6. A multivariate analysis showed a clustering of countries in three groups: (1) high Gini coefficients comprised mainly African countries; (2) moderate Gini coefficients comprised mainly South-East Asian, Central and South American countries; (3) low Gini coefficients comprised mainly Western countries, Japan, and Korea. The analysis also showed that inequality in distribution of nurses was correlated with other indices of health and inequality such as the Human Development Index, maternal mortality, and life expectancy.

Conclusions
This study showed that there is a high level of geographic inequality in the distribution of nurses at subnational level. Inequalities in nursing distribution are multifactorial, to improve access to nurses, policies should be bundled, tailored to the local context and tackle the various root causes for inequalities.
Health communication in and out of public health emergencies: to persuade or to inform?
Authors: Oxman Andrew D. , Fretheim Atle , Lewin Simon , Flottorp Signe , Glenton Claire , Helleve Arnfinn , Vestrheim Didrik Frimann , Iversen Bjørn Gunnar , Rosenbaum Sarah E. 
Published: March 2022

AbstractMuch health communication during the COVID-19 pandemic has been designed to persuade people more than to inform them. For example, messages like “masks save lives” are intended to compel people to wear face masks, not to enable them to make an informed decision about whether to wear a face mask or to understand the justification for a mask mandate. Both persuading people and informing them are reasonable goals for health communication. However, those goals can sometimes be in conflict. In this article, we discuss potential conflicts between seeking to persuade or to inform people, the use of spin to persuade people, the ethics of persuasion, and implications for health communication in the context of the pandemic and generally. Decisions to persuade people rather than enable them to make an informed choice may be justified, but the basis for those decisions should be transparent and the evidence should not be distorted. We suggest nine principles to guide decisions by health authorities about whether to try to persuade people.