NUDT5-Determines the fate of head and neck squamous cell carcinoma cells under endoplasmic reticulum stress by catalyzing nuclear ATP production to promote DNA repair.

OBJECTIVES: NUDT5 is the only discovered enzyme that catalyses ATP production in cell nuclei. In this study, we investigate the character of NUDT5 in head and neck squamous cell carcinoma (HNSCC) cells under endoplasmic reticulum (ER) stress. METHODS: The formation of ER stress was confirmed in HNSCC cells using Real-time PCR and Western blot techniques. The expression of NUDT5 was modified by transfecting HNSCC cells with siRNA and plasmids, respectively. The effects of NUDT5 manipulation were assessed using various methods including cell counting kit-8 assay, western blotting, RNA sequencing, Immunofluorescence Microscopy analysis, cell cycle analysis and nucleic ATP measurement, and a xenograft mouse model. RESULTS: In this study, we found that the expression of NUDT5 proteins was upregulated under ER stress conditions in HNSCC cells. Knocking down NUDT5 under ER stress could hinder nuclear ATP generation and thus induce more DNA damage and apoptosis of HNSCC cells. Only the wild-type NUDT5 or ATP catalysis active mutant T45A-NUDT5, rather than the ATP catalysis null mutant T45D-NUDT5, could directly rescue nuclear ATP depletion caused by NUDT5 inhibition and protect HNSCC cells from DNA damage and cell apoptosis. Finally, in vivo studies showed that knocking down NUDT5 in ER-stressed conditions could significantly inhibit tumour growth. CONCLUSION: Our study demonstrated for the first time that NUDT5 guaranteed the integrity of DNA under ER stress-triggered DNA damage by catalysing nuclear ATP production. Our findings offer new insights into how the energy supply in cell nuclei fuels cancer cell survival in stressful microenvironment.

Trends and Hotspots in Nanoparticles for the Targeted Delivery of Nucleic Acids: A Ten-Year Bibliometric Study.

Nanoparticles for the gene therapy field have seen remarkable progress over the last 10 years; however, low delivery efficiency and other reasons impede the clinical translation of nanocarriers. Therefore, a summary of hotspots and trends in this field is needed to promote further research development. In this research, from 2011 to 2021, 1,221 full records and cited references of Web of Science-indexed manuscripts regarding nanoparticle-targeted delivery systems have been analyzed by CiteSpace, VOSviewer, and MapEquation. In these software, keywords co-occurrence networks, alluvial diagram, co-citation networks, and structural variation analysis were carried out to emphasize the scientific community's focus on nanomedicine of targeted delivering of nucleic acids. Keywords such as transfection efficiency, tumor cell, membrane antigen, and siRNA delivery were highlighted in the density map from VOSviewer. In addition, an alluvial flow diagram was constructed to detect changes in concepts. In the co-citation network, cluster 1 (exosomes) and cluster 17 (genome editing) were new research fields, and the efforts in modifying nanoparticles were revealed in the structural variation analysis. Aptamer and SELEX (systematic evolution of ligands by exponential enrichment) represented a helpful system in targeted delivery. These results indicated that the transfection efficiency of nanocarriers required continuous improvements. With the approval of several nucleic acid drugs, a new content of nanoparticle carriers is to introduce gene-editing technology, especially CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9). In addition, exosomes have great potential as targeted nanoparticles. By mapping the knowledge domains of nanomedicine in targeted delivering of nucleic acids, this study analyzed the intellectual structure of this domain in the recent 10 years, highlighting classical modifications on nanoparticles and estimating future trends for researchers and decision-makers interested in this field.

Emerging trends in photodynamic therapy for head and neck cancer: A 10-year bibliometric analysis based on CiteSpace.

BACKGROUND: Head and neck cancer (HNC) was the seventh most common cancer worldwide. Photodynamic therapy (PDT) is a clinically approved, minimally invasive treatment, which was shown to be effective in the treatment of head and neck cancer and potentially malignant disorders. We used a bibliometric analysis to analyze the publications of radiomics in oncology to clearly illustrate the current situation and future trends and encourage more researchers to participate in radiomics research in oncology. METHODS: Publications for Photodynamic therapy in for head and neck cancer and potentially malignant disorders were downloaded from the Web of Science Core Collection (WoSCC). CiteSpace was used for a bibliometric analysis of countries, institutions, journals, authors, keywords, and references pertaining to this field. The state of research and areas of focus were analyzed through burst detection. RESULTS: A total of 1002 studies were used for analysis on CiteSpace. The USA is in first place by number of publications. Hopper C, was the most prolific author, and the author with the most citations was Chen XY. Among the journals and the co-cited journals, "Photodiagnosis and Photodynamic Therapy" was the first. "Nanoparticle" showed the highest burst strength level and materials research is major area of focus in this field. CONCLUSIONS: This bibliometric analysis of photodynamic therapy in head and neck cancer, provides a visual analysis of publications in this field. The conclusion of the current research in this field was that it focused on the research of photosensitizers, particularly nanomaterials and targeted therapies.

Oral cancer cells affect pancreatic ß-cell function through transmissible endoplasmic reticulum stress.

OBJECTIVES: In this study, we aimed to investigate whether oral cancer cells affect pancreatic ß-cells function through transmissible endoplasmic reticulum stress (TERS). METHODS: Tunicamycin (TM) was selected as the endoplasmic reticulum stress (ERS) inducer. The human oral cancer cell lines CAl-27 and SCC-25 were selected as the donor cells, and mouse insulinoma 6 (MIN6) cell lines were chosen as the recipient cells. Quantitative real-time polymerase chain reaction (qPCR) and Western blot (WB) analysis were used to detect ERS markers and insulin expression. The TdT-mediated dUTP nick-end labeling (TUNEL) method was applied to detect apoptosis levels. The clone formation method was utilized to detect cell proliferation capability. The secretory function of pancreatic ß-cells was detected with an enzyme linked immunosorbent assay (ELISA) kit and a bicinchoninic acid (BCA) kit. RESULTS: The MIN6 cells were subjected to TM stimulation. qPCR and WB analysis revealed that ERS markers were upregulated. This result implied that the MIN6 cells can induce ERS. The supernatant of oral cancer cells under ERS was added to the MIN6 cells. qPCR and WB analysis showed that the oral cancer cells that had been subjected to ERS could induce ERS in the MIN6 cells, that is, the phenomenon of TERS occurred. The TUNEL assay indicated that the apoptosis of the MIN6 cells increased under TERS. The clone formation assay demonstrated that the proliferation capability of the MIN6 cells decreased under TERS. qPCR and WB analysis revealed that under TERS, insulin synthesis by the MIN6 cells decreased and insulin synthesis was inhibited at the translation level. The ELISA and BCA kits demonstrated that insulin secretion by the MIN6 cells was reduced under TERS. CONCLUSIONS: Oral cancer cells can affect pancreatic ß-cells through TERS, resulting in increased apoptosis, decreased viability, and reduced insulin secretion and synthesis capability.

Radiomics in Oncology: A 10-Year Bibliometric Analysis.

OBJECTIVES: To date, radiomics has been applied in oncology for over a decade and has shown great progress. We used a bibliometric analysis to analyze the publications of radiomics in oncology to clearly illustrate the current situation and future trends and encourage more researchers to participate in radiomics research in oncology. METHODS: Publications for radiomics in oncology were downloaded from the Web of Science Core Collection (WoSCC). WoSCC data were collected, and CiteSpace was used for a bibliometric analysis of countries, institutions, journals, authors, keywords, and references pertaining to this field. The state of research and areas of focus were analyzed through burst detection. RESULTS: A total of 7,199 pieces of literature concerning radiomics in oncology were analyzed on CiteSpace. The number of publications has undergone rapid growth and continues to increase. The USA and Chinese Academy of Sciences are found to be the most prolific country and institution, respectively. In terms of journals and co-cited journals, Scientific Reports is ranked highest with respect to the number of publications, and Radiology is ranked highest among co-cited journals. Moreover, Jie Tian has published the most publications, and Phillipe Lambin is the most cited author. A paper published by Gillies et al. presents the highest citation counts. Artificial intelligence (AI), segmentation methods, and the use of radiomics for classification and diagnosis in oncology are major areas of focus in this field. Test-retest statistics, including reproducibility and statistical methods of radiomics research, the relation between genomics and radiomics, and applications of radiomics to sarcoma and intensity-modulated radiotherapy, are frontier areas of this field. CONCLUSION: To our knowledge, this is the first study to provide an overview of the literature related to radiomics in oncology and may inspire researchers from multiple disciplines to engage in radiomics-related research.

Research on neck dissection for oral squamous-cell carcinoma: a bibliometric analysis.

Neck dissection for oral squamous-cell carcinoma (OSCC) is a clinically controversial issue and has therefore been the subject of abundant research. However, no one has performed a bibliometric study on this topic to date. The aim of this study was to assess the development of research on neck dissection for OSCC in terms of the historical evolution, current hotspots and future directions, particularly including research trends and frontiers from 2010 to 2019. Literature records related to research on neck dissection for OSCC were retrieved from the Web of Science Core Collection (WoSCC). CiteSpace was used as a tool to perform a bibliometric analysis of this topic. The survey included 2 096 papers. "Otorhinolaryngology" was the most popular research area. The most active institutions and countries were Memorial Sloan Kettering Cancer Center and the USA, respectively. Shah J.P. was the most cited author. Among the six identified "core journals", Head & Neck ranked first. The top three trending keywords were 'invasion', 'upper aerodigestive' and 'negative neck'. 'D'Cruz AK (2015)' was the most cited and the strongest burst reference in the last decade. The study evaluated the effect on survival of elective versus therapeutic neck dissection in patients with lateralized early-stage OSCC. The depth of invasion and the management of N0 OSCC were research frontiers in this field. The present study provides a comprehensive bibliometric analysis of research on neck dissection for OSCC, which will assist investigators in exploring potential research directions.