NRF2, a redox sensitive transcription factor, is up-regulated in head and neck squamous cell carcinoma (HNSCC), however, the associated impact and regulatory mechanisms remain unclear.
The protein ...expression of NRF2 in HNSCC specimens was examined by IHC. The regulatory effect of c-MYC on NRF2 was validated by ChIP-qPCR, RT-qPCR and western blot. The impacts of NRF2 on malignant progression of HNSCC were determined through genetic manipulation and pharmacological inhibition
and
. The gene-set enrichment analysis (GSEA) on expression data of cDNA microarray combined with ChIP-qPCR, RT-qPCR, western blot, transwell migration/ invasion, cell proliferation and soft agar colony formation assays were used to investigate the regulatory mechanisms of NRF2.
NRF2 expression is positively correlated with malignant features of HNSCC. In addition, carcinogens, such as nicotine and arecoline, trigger c-MYC-directed NRF2 activation in HNSCC cells. NRF2 reprograms a wide range of cancer metabolic pathways and the most notable is the pentose phosphate pathway (PPP). Furthermore, glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) are critical downstream effectors of NRF2 that drive malignant progression of HNSCC; the coherently expressed signature NRF2/G6PD/TKT gene set is a potential prognostic biomarker for prediction of patient overall survival. Notably, G6PD- and TKT-regulated nucleotide biosynthesis is more important than redox regulation in determining malignant progression of HNSCC.
Carcinogens trigger c-MYC-directed NRF2 activation. Over-activation of NRF2 promotes malignant progression of HNSCC through reprogramming G6PD- and TKT-mediated nucleotide biosynthesis. Targeting NRF2-directed cellular metabolism is an effective strategy for development of novel treatments for head and neck cancer.
Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays ...a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMT-related circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.
This work presents polymer photovoltaic devices based on poly(3-hexylthiophene) (P3HT) and TiO2 nanorod hybrid bulk heterojunctions. Interface modification of a TiO2 nanorod surface is conducted to ...yield a very promising device performance of 2.20% with a short circuit current density (J sc) of 4.33 mA/cm2, an open circuit voltage (V oc) of 0.78 V, and a fill factor (FF) of 0.65 under simulated A.M. 1.5 illumination (100 mW/cm2). The suppression of recombination at P3HT/TiO2 nanorod interfaces by the attachment of effective ligand molecules substantially improves device performance. The correlation between surface photovoltage and hybrid morphology is revealed by scanning Kelvin probe microscopy. The proposed method provides a new route for fabricating low-cost, environmentally friendly polymer/inorganic hybrid bulk heterojunction photovoltaic devices.
The type 2 transmembrane serine protease matriptase is involved in many pathophysiological processes probably via its enzymatic activity, which depends on the dynamic relationship between zymogen ...activation and protease inhibition. Matriptase shedding can prolong the life of enzymatically active matriptase and increase accessibility to substrates. We show here that matriptase shedding occurs via a de novo proteolytic cleavage at sites located between the SEA domain and the CUB domain. Point or combined mutations at the four positively charged amino acid residues in the region following the SEA domain allowed Arg-186 to be identified as the primary cleavage site responsible for matriptase shedding. Kinetic studies further demonstrate that matriptase shedding is temporally coupled with matriptase zymogen activation. The onset of matriptase shedding lags one minute behind matriptase zymogen activation. Studies with active site triad Ser-805 point mutated matriptase, which no longer undergoes zymogen activation or shedding, further suggests that matriptase shedding depends on matriptase zymogen activation, and that matriptase proteolytic activity may be involved in its own shedding. Our studies uncover an autonomous mechanism coupling matriptase zymogen activation, proteolytic activity, and shedding such that a proportion of newly generated active matriptase escapes HAI-1-mediated rapid inhibition by shedding into the extracellular milieu.
Mental health is a major public health issue that affects social development. This study aims to explore the psychological state of residents of Hainan Island and its influencing factors during the ...COVID-19 pandemic and to provide a scientific basis for the formulation of psychological counseling measures to be used after the pandemic. We used the nonprobability snowball sampling method to conduct an online survey from February 21 to February 28, 2020, and collected a sample of 533 respondents. Using a binary logistic regression model and network analysis, the psychological state of residents and the main factors were analyzed during the concentrated outbreak of COVID-19 (from January 20 to February 16, 2020). The study found that during the pandemic, 92.7% of the respondents were in a poor state of mind, and 54.2% experienced severe psychological stress. The mental state is spatially expressed as a pattern of "high in the middle and low in the surroundings." Second, within the four-week sample, the overall psychological tension showed an inverted U-shaped trend. Respondents feeling stressed were most common in the second week, when they accounted for 87.99% of the total. Third, individual characteristics such as gender, age, fixed expenditure, and family size significantly affect the mental state. Women, the elderly, residents with fixed expenditures, and residents with large families are at greater risk of psychological stress. Finally, external factors such as the distance between residents and the location of cases and the node degree of the pandemic transmission network have a significant impact on the psychological state. However, residents in the least developed areas of Hainan Island, which are far away from active cases and have a low node degree, are more prone to psychological pressure. The government needs to pay special attention to these groups when constructing a long-term mechanism of psychological crisis intervention and increase public health resource investment in underdeveloped areas.
Malpractice claims place heavy economic and emotional burdens on both dentists and patients. Recently, medical malpractice lawsuits are decreasing in prevalence but increasing in severity. The ...percentage of dental malpractice payments is also growing among the health profession. The present study aimed to explore criminal convictions in dental malpractice litigation and to analyze the factors affecting the judgment in dental disputes in Taiwan.
The keywords “dentist,” “professional negligence,” “medical malpractice,” and “professional liability” were used to search Taiwan's Law and Regulations Retrieving System for criminal dental malpractice cases in all district courts from January 1, 2000 to June 30, 2021. The eligible judgments were summarized and analyzed.
Overall, 425 cases were identified, with 28 dental disputes included in the final analysis. The dentists lost in 10 cases (35.7%). The average claim time was 36.75 ± 16.34 months. Taipei and Taichung dealt with more lawsuit cases (n = 8). Local clinics were the most common institution of the defendants (75%) and had the highest number of convictions (n = 9). Implant dentistry was the most common specialty involved. Expert testimony of the Medical Review Committee (MRC) had a high K coefficient of agreement with court judgments regarding professional negligence (p < 0.001).
The overall criminal conviction rate was 35.7%. Implant therapy and local clinics had the highest rate of lawsuits and a considerably higher conviction rate. All guilty dentists were fined or given probation. The court judgments were highly consistent with the expert testimony of the MRC.
The kidney is vital in maintaining fluid, electrolyte, and acid-base balance. Kidney-related diseases, which are an increasing public health issue, can happen to people of any age and at any time. ...Circular RNAs (circRNAs) are endogenous RNA that are produced by selective RNA splicing and are involved in progression of various diseases. Studies have shown that various kidney diseases, including renal cell carcinoma, acute kidney injury, and chronic kidney disease, are linked to circRNAs. This review outlines the characteristics and biological functions of circRNAs and discusses specific studies that provide insights into the function and potential of circRNAs for application in the diagnosis and treatment of kidney-related diseases.
The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The ...aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME.
Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs
and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics.
patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs.
The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity
and
, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs.
The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.
We assessed the quality of life (QoL) and pregnancy outcomes of in vitro fertilization (IVF) treatment among infertile women with endometriosis, as compared to infertile women without endometriosis.
...Eighty-one (81) endometriosis women (with 142 embryo transfer ET cycles) and 605 non-endometriosis women (with 1063 ET cycles) were included. QoL was measured by FertiQoL at the date before ET. Pregnancy outcomes included biochemical pregnancy, ongoing pregnancy and live birth. Generalized estimating equation analyses were performed to assess the association between QoL and IVF pregnancy.
Endometriosis-affected women had significantly lower QoL, as indicated by mind/body, treatment environment and total treatment scores, and total scores of FertiQoL (p < .05), compared to those without endometriosis. Among non-endometriosis women, QoL scores were significantly associated with successful IVF pregnancy; with one unit increase in QoL scores as measured by emotional domain of FertiQoL, the probabilities of ongoing pregnancy and live birth significantly increased by 2.5% and 2.8%, respectively (p < .05). This association was also observed among endometriosis women but it did not reach statistical significance.
Lower QoL among women with endometriosis versus non-endometriosis during IVF treatment highlights the importance of developing strategies to improve their QoL, which may enhance following pregnancy rates in this population.
Renal cell carcinoma (RCC) is one of the most prevalent cancers diseases in the worldwide. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. LINC00460 has ...been reported to participate in many kinds of malignancies and promotes cancer progressions. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to explore the potential function and regulation mechanism of LINC00460 in RCC. We analysed the LINC00460 expression and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases. LINC00460 level in normal renal cell line and RCC cell lines were examined by qRT-PCR. We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression of LINC00460 both in RCC tissues and cell. RCC patients with elevated LINC00460 expression have shorter survival. Up-expression of LINC00460 promoted cell proliferation, invasion and migration, meanwhile down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study showed that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT.
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