Development and validation of radiomics nomogram for metastatic status of epithelial ovarian cancer.

To develop and validate an enhanced CT-based radiomics nomogram for evaluating preoperative metastasis risk of epithelial ovarian cancer (EOC). One hundred and nine patients with histologically confirmed EOC were retrospectively enrolled. The volume of interest (VOI) was delineated in preoperative enhanced CT images, and 851 radiomics features were extracted. The radiomics features were selected by the least absolute shrinkage and selection operator (LASSO), and the rad-score was calculated using the formula of the radiomics label. A clinical model, radiomics model, and combined model were constructed using the logistic regression classification algorithm. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the diagnostic performance of the models. Seventy-five patients (68.8%) were histologically confirmed to have metastasis. Eleven optimal radiomics features were retained by the LASSO algorithm to develop the radiomic model. The combined model for evaluating metastasis of EOC achieved area under the curve (AUC) values of 0.929 (95% CI 0.8593-0.9996) in the training cohort and 0.909 (95% CI 0.7921-1.0000) in the test cohort. To facilitate clinical use, a radiomic nomogram was built by combining the clinical characteristics with rad-score. The DCA indicated that the nomogram had the most significant net benefit when the threshold probability exceeded 15%, surpassing the benefits of both the treat-all and treat-none strategies. Compared with clinical model and radiomics model, the radiomics nomogram has the best diagnostic performance in evaluating EOC metastasis. The nomogram is a useful and convenient tool for clinical doctors to develop personalized treatment plans for EOC patients.

Development and external validation of a perioperative clinical model for predicting myocardial injury after major abdominal surgery: A retrospective cohort study.

Purpose: We aimed to develop and validate a predictive model for myocardial injury in individuals undergoing major abdominal surgery. Methods: This multicenter retrospective cohort analysis included 3546 patients aged ≥45 years who underwent major abdominal surgeries at two Chinese tertiary hospitals. The primary outcome was myocardial injury after noncardiac surgery (MINS), defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The LASSO algorithm and logistic regression were used to construct a predictive model for postoperative MINS in the development cohort, and the performance of this prediction model was validated in an external independent cohort. Results: A total of 3546 patients were included in our study. MINS manifested in 338 (9.53 %) patients after surgery. The definitive predictive model for MINS was developed by incorporating age, American Society of Anesthesiologists (ASA) classification, preoperative hemoglobin concentration, preoperative serum ALB concentration, blood loss, total infusion volume, and operation time. The area under the curve (AUC) of our model was 0.838 and 0.821 in the derivation and validation cohorts, respectively. Conclusions: Preoperative hemoglobin levels, preoperative serum ALB concentrations, infusion volume, and blood loss are independent predictors of MINS. Our predictive model can prove valuable in identifying patients at moderate-to-high risk prior to non-cardiac surgery.

SEnSCA: Identifying possible ligand-receptor interactions and its application in cell-cell communication inference.

Multicellular organisms have dense affinity with the coordination of cellular activities, which severely depend on communication across diverse cell types. Cell-cell communication (CCC) is often mediated via ligand-receptor interactions (LRIs). Existing CCC inference methods are limited to known LRIs. To address this problem, we developed a comprehensive CCC analysis tool SEnSCA by integrating single cell RNA sequencing and proteome data. SEnSCA mainly contains potential LRI acquisition and CCC strength evaluation. For acquiring potential LRIs, it first extracts LRI features and reduces the feature dimension, subsequently constructs negative LRI samples through K-means clustering, finally acquires potential LRIs based on Stacking ensemble comprising support vector machine, 1D-convolutional neural networks and multi-head attention mechanism. During CCC strength evaluation, SEnSCA conducts LRI filtering and then infers CCC by combining the three-point estimation approach and single cell RNA sequencing data. SEnSCA computed better precision, recall, accuracy, F1 score, AUC and AUPR under most of conditions when predicting possible LRIs. To better illustrate the inferred CCC network, SEnSCA provided three visualization options: heatmap, bubble diagram and network diagram. Its application on human melanoma tissue demonstrated its reliability in CCC detection. In summary, SEnSCA offers a useful CCC inference tool and is freely available at https://github.com/plhhnu/SEnSCA.

Contrast-enhanced CT radiomics for preoperative prediction of stage in epithelial ovarian cancer: a multicenter study.

BACKGROUND: Preoperative prediction of International Federation of Gynecology and Obstetrics (FIGO) stage in patients with epithelial ovarian cancer (EOC) is crucial for determining appropriate treatment strategy. This study aimed to explore the value of contrast-enhanced CT (CECT) radiomics in predicting preoperative FIGO staging of EOC, and to validate the stability of the model through an independent external dataset. METHODS: A total of 201 EOC patients from three centers, divided into a training cohort (n = 106), internal (n = 46) and external (n = 49) validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening radiomics features. Five machine learning algorithms, namely logistic regression, support vector machine, random forest, light gradient boosting machine (LightGBM), and decision tree, were utilized in developing the radiomics model. The optimal performing algorithm was selected to establish the radiomics model, clinical model, and the combined model. The diagnostic performances of the models were evaluated through receiver operating characteristic analysis, and the comparison of the area under curves (AUCs) were conducted using the Delong test or F-test. RESULTS: Seven optimal radiomics features were retained by the LASSO algorithm. The five radiomics models demonstrate that the LightGBM model exhibits notable prediction efficiency and robustness, as evidenced by AUCs of 0.83 in the training cohort, 0.80 in the internal validation cohort, and 0.68 in the external validation cohort. The multivariate logistic regression analysis indicated that carcinoma antigen 125 and tumor location were identified as independent predictors for the FIGO staging of EOC. The combined model exhibited best diagnostic efficiency, with AUCs of 0.95 in the training cohort, 0.83 in the internal validation cohort, and 0.79 in the external validation cohort. The F-test indicated that the combined model exhibited a significantly superior AUC value compared to the radiomics model in the training cohort (P < 0.001). CONCLUSIONS: The combined model integrating clinical characteristics and radiomics features shows potential as a non-invasive adjunctive diagnostic modality for preoperative evaluation of the FIGO staging status of EOC, thereby facilitating clinical decision-making and enhancing patient outcomes.

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis.

Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta-analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P < 0.00001] and stroke volume [MD = 6.59, 95% CI (3.22, 9.96), P = 0.0001] and significantly reduced left ventricular end-systolic volume [standard mean difference (SMD) = -0.52, 95% CI (-0.67, -0.37), P < 0.00001], left ventricular end-diastolic volume index [SMD = -1.24, 95% CI (-1.61, -0.86), P < 0.00001], and left ventricular end-systolic volume index [SMD = -1.06, 95% CI (-1.43, -0.70), P < 0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD = -1.08, 95% CI (-1.60, -0.56), P < 0.0001], N-terminal pro-brain natriuretic peptide [SMD = -0.99, 95% CI (-1.41, -0.56), P < 0.00001], and interleukin-6 [SMD = -0.61, 95% CI (-0.86, -0.35), P < 0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR) = 1.24, 95% CI (1.12, 1.39), P < 0.0001], hypokalaemia [RR = 1.57, 95% CI (1.08, 2.28), P = 0.02], headache [RR = 1.89, 95% CI (1.50, 2.39), P < 0.00001], atrial fibrillation [RR = 1.31, 95% CI (1.12, 1.52), P = 0.0005], and premature ventricular complexes [RR = 1.86, 95% CI (1.27, 2.72), P = 0.001]. In addition, levosimendan reduced all-cause mortality [RR = 0.83, 95% CI (0.74, 0.94), P = 0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

Feasibility of using 8 mL of iodinated contrast media in cerebral computed tomographic angiography with a dual-layer spectral detector.

Background: Virtual monoenergetic images (VMIs) at a low energy level can improve image quality when the amount of iodinated contrast media (CM) is reduced. The purpose was to evaluate the feasibility of using an extremely low CM volume and injection rate in cerebral computed tomography angiography (CTA) on a dual-layer spectral detector computed tomography (CT). Methods: Patients who were clinically suspected of intracranial aneurysm or cerebrovascular diseases were included in our study (from June to November 2022). In this prospective study, 80 patients were randomly enrolled into group A (8 mL of CM with a 1-mL/s flow rate) or group B (40 mL of CM with 4-mL/s flow rate). The VMIs at 40-70 keV in group A and polychromatic conventional images in the 2 groups were reconstructed. CT attenuation, image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were evaluated via the t-test or Mann-Whitney test (2 groups), while analysis of variance or Kruskal-Wallis test (multiple groups). Subjective image quality was assessed on a 5-point scale. Results: In group A, the subjective image quality score, CT attenuation, and CNR of the internal carotid artery (ICA) and middle cerebral artery (MCA) were the highest on VMIs at 40 keV. The image noise on VMIs at 40 keV was 5.08±0.84 Hounsfield units. The subjective image quality score, CT value of the ICA, MCA, and cerebral parenchyma on VMIs at 40 keV in group A were similar to those in group B (all P values >0.05). Compared to those in group B, the VMIs at 40 keV in group A demonstrated a significantly higher mean SNR and CNR of the ICA (mean SNR: 46.22±20.18 vs. 34.32±12.40, P=0.002; CNR: 55.47±13.43 vs. 46.18±12.30, P=0.002) and MCA [SNR: 13.66 (9.78, 20.29) vs. 9.99 (7.53, 14.00), P=0.003; CNR: 47.00±12.71 vs. 39.45±10.47, P=0.005]. Conclusions: Cerebral CTA on VMIs at 40 keV with 8 mL of CM and a 1-mL/s injection rate can provide diagnostic image quality.

Transcriptome-wide N6-methyladenosine (m6A) methylation profiling of long non-coding RNAs in ovarian endometriosis.

N6-methyladenosine (m6A) methylation is the most prevalent internal epigenetic posttranscriptional mechanism for regulating mammalian RNA. Despite recent advances in determining the biological functions of m6A methylation, its association with the pathology of ovarian endometriosis remains uncertain. Herein, we performed m6A transcriptome-wide profiling to identify key lncRNAs with m6A modification involved in ovarian endometriosis development by bioinformatics analysis. We found the total m6A level was lower in ovarian endometriosis than in normal endometrium samples, with 9663 m6A peaks associated with 8989 lncRNAs detected in ovarian endometriosis and 9902 m6A peaks associated with 9210 lncRNAs detected in normal endometrium samples. These m6A peaks were primarily enriched within AAACU motifs. Functional enrichment analysis indicated that pathways involving the regulation of adhesion and development were significantly enriched in these differentially methylated lncRNAs. The regulatory relationships among lncRNAs, microRNAs (miRNAs), and mRNAs were identified by competing endogenous RNA (ceRNA) analysis and determination of the network regulating lncRNA-mRNA expression. Several specific lncRNA, including LINC00665, LINC00937, FZD10-AS1, DIO3OS and GATA2-AS1 which were differently expressed and modified by m6A, were validated using qRT-PCR and its interaction with infiltrating immune cells was explored. Furthermore, we found LncRNA DIO3OS promotes the invasion and migration of Human endometrial stromal cells (THESCs) and ALKBH5 regulates the expression of the lncRNA DIO3OS through m6A modification in vitro. Our study firstly revealed the transcriptome-wide map of m6A modification in lncRNAs of ovarian endometriosis. These findings may enable the determination of the underlying mechanism governing the pathogenesis of ovarian endometriosis and provide theoretical basis for further deeper research on the role of m6A in the development of ovarian endometriosis.

Regulated secretion of mutant p53 negatively affects T lymphocytes in the tumor microenvironment.

Several studies have demonstrated the role of the oncogenic mutant p53 in promoting tumor progression; however, there is limited information on the effects of secreted oncogenic mutant p53 on the tumor microenvironment and tumor immune escape. In this study, we found that secretion of mutant p53, determined by exosome content, is dependent on its N-terminal dileucine motif via its binding to ß-adaptin, and inhibited by the CHK2-mediated-Ser 20 phosphorylation. Moreover, we observed that the mutant p53 caused downregulation and dysfunction of CD4+ T lymphocytes in vivo and downregulated the levels and activities of rate-limiting glycolytic enzymes in vitro. Furthermore, inhibition of mutant p53 secretion by knocking down AP1B1 or mutation of dileucine motif could reverse the quantity and function of CD4+ T lymphocytes and restrain the tumor growth. Our study demonstrates that the tumor-derived exosome-mediated secretion of oncogenic mutant p53 inhibits glycolysis to alter the immune microenvironment via functional suppression of CD4+ T cells, which may be the underlying mechanism for tumor immune escape. Therefore, targeting TDE-mediated p53 secretion may serve as a potential therapeutic target for cancer treatment.

Application of medical imaging in ovarian cancer: a bibliometric analysis from 2000 to 2022.

Background: Ovarian cancer (OC) is the most lethal tumor within the female reproductive system. Medical imaging plays a significant role in diagnosis and monitoring OC. This study aims to use bibliometric analysis to explore the current research hotspots and collaborative networks in the application of medical imaging in OC from 2000 to 2022. Methods: A systematica search for medical imaging in OC was conducted on the Web of Science Core Collection on August 9, 2023. All reviews and articles published from January 2000 to December 2022 were downloaded, and an analysis of countries, institutions, journals, keywords, and collaborative networks was perfomed using CiteSpace and VOSviewer. Results: A total of 5,958 publications were obtained, demonstrating a clear upward trend in annual publications over the study peroid. The USA led in productivity with 1,373 publications, and Harvard University emerged as the most prominent institution with 202 publications. Timmerman D was the most prolific contributor with 100 publications, and Gynecological Oncology led in the number of publications with 296. The top three keywords were "ovarian cancer" (1,256), "ultrasound" (725), and "diagnosis" (712). In addition, "pelvic masses" had the highest burst strength (25.5), followed by "magnetic resonance imaging (MRI)" (21.47). Recent emergent keywords such as "apoptosis", "nanoparticles", "features", "accuracy", and "human epididymal protein 4 (HE 4)" reflect research trends in this field and may become research hotspots in the future. Conclusion: This study provides a comprehensive summary of the key contributions of OC imaging to field's development over the past 23 years. Presently, primary areas of OC imaging research include MRI, targeted therapy of OC, novel biomarker (HE 4), and artificial intelligence. These areas are expected to influence future research endeavors in this field.

The application of radiology for dilated cardiomyopathy diagnosis, treatment, and prognosis prediction: a bibliometric analysis.

Background: Radiology plays a highly crucial role in the diagnosis, treatment, and prognosis prediction of dilated cardiomyopathy (DCM). Related research has increased rapidly over the past few years, but systematic analyses are lacking. This study thus aimed to provide a reference for further research by analyzing the knowledge field, development trends, and research hotspots of radiology in DCM using bibliometric methods. Methods: Articles on the radiology of DCM published between 2002 and 2021 in the Web of Science Core Collection database (WoSCCd) were searched and analyzed. Data were retrieved and analyzed using CiteSpace V, VOSviewer, and Scimago Graphic software, and included the name, research institution, and nationality of authors; journals of publication; and the number of citations. Results: A total of 4,257 articles were identified on radiology of DCM from WoSCCd. The number of articles published in this field has grown steadily from 2002 to 2021 and is expected to reach 392 annually by 2024. According to subfields, the number of papers published in cardiac magnetic resonance field increased steadily. The authors from the United States published the most (1,364 articles, 32.04%) articles. The author with the most articles published was Bax JJ (54 articles, 1.27%) from Leiden University Medical Center. The most cited article was titled "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure", with 138 citations. Citation-based clustering showed that arrhythmogenic cardiomyopathy, T1 mapping, and endomyocardial biopsy are the current hots pots for research in DCM radiology. The most frequently occurring keyword was "dilated cardiomyopathy". The keyword-based clusters mainly included "late gadolinium enhancement", "congestive heart failure", "cardiovascular magnetic resonance", "sudden cardiac death", "ventricular arrhythmia", and "cardiac resynchronization therapy". Conclusions: The United States and Northern Europe are the most influential countries in research on DCM radiology, with many leading distinguished research institutions. The current research hots pots are myocardial fibrosis, risk stratification of ventricular arrhythmia, the prognosis of cardiac resynchronization therapy (CRT) treatment, and subtype classification of DCM.

Remote ischemic preconditioning and clinical outcomes after pediatric cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: The benefit of remote ischemia preconditioning (RIPreC) in pediatric cardiac surgery is unclear. The objective of this systematic review and meta-analysis was to examine the effectiveness of RIPreC in reducing the duration of mechanical ventilation and intensive care unit (ICU) length of stay after pediatric cardiac surgery. METHODS: We searched PubMed, EMBASE and the Cochrane Library from inception to December 31, 2022. Randomized controlled trials comparing RIPreC versus control in children undergoing cardiac surgery were included. The risk of bias of included studies was assessed using the Risk of Bias 2 (RoB 2) tool. The outcomes of interest were postoperative duration of mechanical ventilation and ICU length of stay. We conducted random-effects meta-analysis to calculate weighted mean difference (WMD) with 95% confidence interval (CI) for the outcomes of interest. We performed sensitivity analysis to examine the influence of intraoperative propofol use. RESULTS: Thirteen trials enrolling 1,352 children were included. Meta-analyses of all trials showed that RIPreC did not reduce postoperative duration of mechanical ventilation (WMD -5.35 h, 95% CI -12.12-1.42) but reduced postoperative ICU length of stay (WMD -11.48 h, 95% CI -20.96- -2.01). When only trials using propofol-free anesthesia were included, both mechanical ventilation duration (WMD -2.16 h, 95% CI -3.87- -0.45) and ICU length of stay (WMD -7.41 h, 95% CI -14.77- -0.05) were reduced by RIPreC. The overall quality of evidence was moderate to low. CONCLUSIONS: The effects of RIPreC on clinical outcomes after pediatric cardiac surgery were inconsistent, but both postoperative mechanical ventilation duration and ICU length of stay were reduced in the subgroup of children not exposed to propofol. These results suggested a possible interaction effect of propofol. More studies with adequate sample size and without intraoperative propofol use are needed to define the role of RIPreC in pediatric cardiac surgery.

De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity.

Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression for further interaction with CtIP for DDR, which promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that de-ubiquitination of SAMHD1 by USP7 promotes DDR to overcome oncogenic stress and affect chemotherapy sensitivity.

Progesterone levels associated with proteinuria in male diabetes mellitus patients: A cross-sectional retrospective study.

INTRODUCTION: The relationship between progesterone (P) and diabetic nephropathy (DKD) is unclear. Herein, we investigated the relationship between progesterone and DKD in men and postmenopausal women with type 2 diabetes mellitus. MATERIALS AND METHODS: We recruited 3,556 male and postmenopausal female patients and obtained the dominance ratio (OR) and corresponding 95% confidence intervals (CIs) associated with progesterone by logistic regression analysis after adjusting for potentially confounding variants. RESULTS: We found that progesterone levels were significantly lower in the massive proteinuria and microproteinuria groups compared with the non-DKD group for male patients. Also, microproteinuria and massive proteinuria prevalence were higher in the first (lowest) progesterone quartile than in the second to fourth quartiles. After adjusting for confounders, compared with the first (lowest) progesterone quartile group, the OR for the second to fourth quartiles in the male microproteinuria subgroup, were: Q2: 0.846 (95% CI: 0.581-1.233, P = 0.385); Q3: 0.667 (95% CI: 0.45-0988, P = 0.044); Q4: 0.597 (95% CI: 0.393-0.907, P = 0.016). In the male massive proteinuria subgroup, the OR for the third quartile group was 0.418 (95% CI: 0.201-0.867, P = 0.019). In contrast, no significant association was detected between progesterone and DKD prevalence in the female group. CONCLUSIONS: Progesterone levels were negatively associated with DKD incidence in hospitalized male patients with type 2 diabetes mellitus.

Biomimetic, Highly Reusable and Hydrophobic Graphene/Polyvinyl Alcohol/Cellulose Nanofiber Aerogels as Oil-Removing Absorbents.

Aerogels have great potential in oil absorption applications; however, many reported aerogels have the drawbacks of a low oil-recovery rate and poor mechanical properties, which limit their application. In this study, highly reusable graphene oxide (GO)/TEMPO-oxidized cellulose nanofiber (TOCN)/polyvinyl alcohol (PVA) aerogels with excellent mechanical properties and with an architecture similar to that of Thalia dealbata stems were fabricated through a three-step process of bidirectional-freezing, freeze-drying, and chemical vapor deposition (CVD) modification. After CVD modification, the modified GTPA (MGTPA) accorded hydrophobicity. The synergistic effects of the three components and the unique biomimetic structure conferred biomimetic-MGTPA (b-MGTPA) with excellent compressible properties. As an adsorbent, b-MGTPA showed a high adsorption capacity (75-151 g/g) for various types of organic solvents. In addition, its high compressibility enables b-MGTPA to have fast and highly efficient recovery of absorbed oil through simple mechanical squeezing and it possesses excellent reusable stability (the oil recovery rate and oil retention rate reached 80% and 91.5%, respectively, after 10 repeated absorption-compression cycles).

Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas.

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emergent coronavirus that has caused frequent zoonotic events through camel-to-human spillover. An effective camelid vaccination strategy is probably the best way to reduce human exposure risk. Here, we constructed and evaluated an inactivated rabies virus-vectored MERS-CoV vaccine in mice, camels, and alpacas. Potent antigen-specific antibody and CD8+ T-cell responses were generated in mice; moreover, the vaccination reduced viral replication and accelerated virus clearance in MERS-CoV-infected mice. Besides, protective antibody responses against both MERS-CoV and rabies virus were induced in camels and alpacas. Satisfyingly, the immune sera showed broad cross-neutralizing activity against the three main MERS-CoV clades. For further characterization of the antibody response induced in camelids, MERS-CoV-specific variable domains of heavy-chain-only antibody (VHHs) were isolated from immunized alpacas and showed potent prophylactic and therapeutic efficacies in the Ad5-hDPP4-transduced mouse model. These results highlight the inactivated rabies virus-vectored MERS-CoV vaccine as a promising camelid candidate vaccine.

Targeted Cancer Therapy Based on Acetylation and Deacetylation of Key Proteins Involved in Double-Strand Break Repair.

DNA double-strand breaks (DSBs) play an important role in promoting genomic instability and cell death. The precise repair of DSBs is essential for maintaining genome integrity during cancer progression, and inducing genomic instability or blocking DNA repair is an important mechanism through which chemo/radiotherapies exert killing effects on cancer cells. The two main pathways that facilitate the repair of DSBs in cancer cells are homologous recombination (HR) and non-homologous end-joining (NHEJ). Accumulating data suggest that the acetylation and deacetylation of DSB repair proteins regulate the initiation and progression of the cellular response to DNA DSBs, which may further affect the chemosensitivity or radiosensitivity of cancer cells. Here, we focus on the role of acetylation/deacetylation in the regulation of ataxia-telangiectasia mutated, Rad51, and 53BP1 in the HR pathway, as well as the relevant roles of PARP1 and Ku70 in NHEJ. Notably, several histone deacetylase (HDAC) inhibitors targeting HR or NHEJ have been demonstrated to enhance chemo/radiosensitivity in preclinical studies. This review highlights the essential role of acetylation/deacetylation in the regulation of DSB repair proteins, suggesting that HDAC inhibitors targeting the HR or NHEJ pathways that downregulate DNA DSB repair genes may be worthwhile cancer therapeutic agents.