The close association of micronutrients with COVID-19.

Objectives: The present study was conducted to explore the performance of micronutrients in the prediction and prevention of coronavirus disease 2019 (COVID-19). Methods: This is an observational case-control study. 149 normal controls (NCs) and 214 COVID-19 patients were included in this study. Fat-soluble and water-soluble vitamins were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and inorganic elements were detected by inductively coupled plasma-mass spectrometry (ICP-MS) analysis. A logistic regression model based on six micronutrients were constructed using DxAI platform. Results: Many micronutrients were dysregulated in COVID-19 compared to normal control (NC). 25-Hydroxyvitamin D3 [25(OH)D3], magnesium (Mg), copper (Cu), calcium (Ca) and vitamin B6 (pyridoxic acid, PA) were significantly independent risk factors for COVID-19. The logistic regression model consisted of 25(OH)D3, Mg, Cu, Ca, vitamin B5 (VB5) and PA was developed, and displayed a strong discriminative capability to differentiate COVID-19 patients from NC individuals [area under the receiver operating characteristic curve (AUROC) = 0.901]. In addition, the model had great predictive ability in discriminating mild/normal COVID-19 patients from NC individuals (AUROC = 0.883). Conclusions: Our study showed that micronutrients were associated with COVID-19, and our logistic regression model based on six micronutrients has potential in clinical management of COVID-19, and will be useful for prediction of COVID-19 and screening of high-risk population.

Association of sleep characteristics with cardiovascular disease risk in adults over 40 years of age: a cross-sectional survey.

Background: The relationship between sleep characteristics and cardiovascular disease (CVD) risk has yet to reach a consistent conclusion, and more research needs to be carried out. This study aimed to explore the relationship between snoring, daytime sleepiness, bedtime, sleep duration, and high-risk sleep patterns with CVD risk. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were collected and analyzed. Multivariable logistic regression was used to evaluate the relationship between snoring, daytime sleepiness, bedtime, sleep duration, high-risk sleep patterns, and CVD risk. Stratified analysis and interaction tests were carried out according to hypertension, diabetes and age. Results: The final analysis contained 6,830 participants, including 1,001 with CVD. Multivariable logistic regression suggested that the relationship between snoring [OR = 7.37,95%CI = (6.06,8.96)], daytime sleepiness [OR = 11.21,95%CI = (9.60,13.08)], sleep duration shorter than 7 h [OR = 9.50,95%CI = (7.65,11.79)] or longer than 8 h [OR = 6.61,95%CI = (5.33,8.19)], bedtime after 0:00 [OR = 13.20,95%CI = (9.78,17.80)] compared to 22:00-22:59, high-risk sleep patterns [OR = 47.73,95%CI = (36.73,62.04)] and CVD risk were statistically significant. Hypertension and diabetes interacted with high-risk sleep patterns, but age did not. Conclusions: Snoring, daytime sleepiness, excessive or short sleep duration, inappropriate bedtime, and high-risk sleep patterns composed of these factors are associated with the CVD risk. High-risk sleep patterns have a more significant impact on patients with hypertension and diabetes.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

Discovery of Insect Attractants Based on the Functional Analyses of Female-Biased Odorant Receptors and Their Orthologs in Two Closely Related Species.

Olfaction plays an instrumental role in host plant selection by phytophagous insects. Helicoverpa assulta and Helicoverpa armigera are two closely related moth species with different host plant ranges. In this study, we first comparatively analyzed the function of 11 female-biased odorant receptors (ORs) and their orthologs in the two species by the Drosophila T1 neuron expression system and then examined the electroantennography responses of the two species to the most effective OR ligands. Behavioral assays using a Y-tube olfactometer indicate that guaiene, the primary ligand of HassOR21-2 and HarmOR21-2, only attracts the females, while benzyl acetone, the main ligand of HassOR35 and HarmOR35, attracts both sexes of the two species. Oviposition preference experiments further confirm that guaiene and benzyl acetone are potent oviposition attractants for the mated females of both species. These findings deepen our understanding of the olfactory coding mechanisms of host plant selection in herbivorous insects and provide valuable attractants for managing pest populations.

Clinical prediction of HBV-associated cirrhosis using machine learning based on platelet and bile acids.

OBJECTIVES: The present study was conducted to evaluate the performance of serum bile acids in the prediction of cirrhosis in chronic hepatitis B (CHB) population. METHODS: Dysregulated metabolites were explored using untargeted and targeted metabolomic analyses. A machine learning model based on platelet (PLT) and several bile acids was constructed using light gradient boosting machine (LightGBM), to differentiate HBV-associated cirrhosis (BAC) from CHB patients. RESULTS: Serum bile acids were dysregulated in BAC compared to CHB patients. The LightGBM model consisted of PLT, TUDCA, UDCA, TLCA, LCA and CA. The model demonstrated a strong discrimination ability in the internal test subset of the training cohort to diagnose BAC from CHB patients (AUC = 0.97). The high diagnostic accuracy of the model was further validated in an independent validation cohort. In addition, the model had high predictive efficacy in discriminating compensated BAC from CHB patients (AUC = 0.89). The performance of the model was better than AST/ALT ratio and the gradient boosting (GB)-based model reported in previous studies. CONCLUSIONS: Our study showed that this LightGBM model based on PLT and 5 bile acids has potential in clinical assessments of CHB progression and will be useful for early detection of cirrhosis in CHB patients.

A Serum Metabolite Classifier for the Early Detection of Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer.

Type 2 diabetes mellitus (T2DM) has been identified as an independent risk factor for hepatocellular cancer (HCC). However, there are no ideal biomarkers for the surveillance and early detection of HCC in the T2DM population at present. In this study, we aimed to explore novel metabolite biomarkers for T2DM-positive [T2DM(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in T2DM(+) HCC patients in untargeted metabolomic analyses. Targeted metabolite analyses confirmed that serum benzoic acid and citrulline were increased, and creatine was decreased in T2DM(+) HCC compared to the T2DM group. A metabolite classifier including benzoic acid, creatine, and citrulline was identified as a novel biomarker for the diagnosis of T2DM(+) HCC, with an area under the ROC curve (AUC) of 0.93 for discriminating T2DM(+) HCC patients from T2DM patients. In addition, the metabolite classifier detected small-size (AUC = 0.94), early-stage (AUC = 0.94), and AFP-negative (AUC = 0.96) tumors with high sensitivity and specificity. The combination of this metabolite classifier and AFP might be useful in the surveillance and early detection of HCC in the T2DM population. In conclusion, this study establishes a novel diagnostic tool for T2DM(+) HCC.

The Potential of Serum Exosomal hsa_circ_0028861 as the Novel Diagnostic Biomarker of HBV-Derived Hepatocellular Cancer.

Hepatitis B virus (HBV)-derived hepatocellular cancer (HCC) is a serious threat to human health, especially in China. There is no highly sensitive and specific HCC biomarker at present, which makes it difficult to detect HCC at the early stage. Serum exosomal circular RNAs (circRNAs) have been reported as novel diagnostic and prognostic biomarkers of cancers. In the present study, we aimed to explore the diagnostic performance of serum exosomal circRNAs for HBV-derived HCC screening. At first, many circRNAs were found to be differentially expressed in the serum exosomes of HCC individuals by microarray analysis. The validation of dysregulated circRNAs by qRT-PCR revealed that serum exosomal hsa_circ_0028861 was decreased in HCC compared to chronic HBV and cirrhosis. Then, hsa_circ_0028861 was identified as a novel biomarker for HCC diagnosis with an area under the ROC curve (AUC) of 0.79 for discriminating HCC from chronic HBV and cirrhosis individuals. Hsa_circ_0028861 was capable of detecting small (AUC = 0.81), early-stage (AUC = 0.82) and AFP-negative [AFP (-)] (AUC = 0.78) tumors as well. The combination of hsa_circ_0028861 and AFP exhibited better diagnostic ability (AUC = 0.86 for discriminating HCC from chronic HBV and cirrhosis). Moreover, bioinformatics prediction suggested that hsa_circ_0028861 might influence HCC progression by regulating its targeted microRNAs (miRNAs) and downstream tumor-related signaling pathways. Collectively, our study reveals a novel diagnostic tool for HBV-derived HCC.

Metabolic Profiling Identified a Novel Biomarker Panel for Metabolic Syndrome-Positive Hepatocellular Cancer.

Metabolic syndrome (MetS) is an independent risk factor for hepatocellular cancer (HCC). Currently, there is no highly sensitive and specific biomarkers for HCC surveillance in MetS population. Metabolomics has been reported as a powerful technology for biomarker discovery. In the present study, we aimed to explore novel biomarkers with high sensitivity and specificity for MetS-positive [MetS(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in MetS(+) HCC individuals. Validation of the dysregulated metabolites by targeted metabolite analyses revealed that serum L-glutamic acid (L-glu), pipecolic acid (PA) and 7-methylguanine (7-mG) were increased in MetS(+) HCC compared to MetS group. Then a biomarker panel including L-glu, PA and alpha-fetoprotein (AFP) was identified as a novel biomarker for the diagnosis of MetS(+) HCC. Receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was 0.87 for discriminating MetS(+) HCC from MetS group. The biomarker panel was capable of detecting small (AUC = 0.82) and early-stage (AUC = 0.78) tumors as well. Moreover, it exhibited great diagnostic performance (AUC = 0.93) for discriminating MetS(+) HCC from other MetS-associated cancers, including colorectal cancer and gastric cancer. Collectively, our study establishes a novel diagnostic tool for MetS(+) HCC.

miR-19 Is a Potential Clinical Biomarker for Gastrointestinal Malignancy: A Systematic Review and Meta-analysis.

OBJECTIVES: To assess the expression and clinical value of miR-19 in gastrointestinal malignancy. Setting. Embase, Web of Science, PubMed, and other databases were retrieved to screen out relevant studies until December 31, 2019. Participants. Gastrointestinal cancer patients with the description of miR-19 expression, as well as the correlation between miR-19 and clinicopathological characteristics or prognosis. Main Outcome Measures. Pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was obtained to determine miR-19 expression in gastrointestinal malignancy and the association between miR-19 and patients' clinical characteristics and survival. RESULTS: Thirty-seven studies were included in this study. miR-19 levels in gastrointestinal malignancy, especially in hepatocellular (OR = 4.88, 95% CI = 2.38-9.99), colorectal (OR = 4.81, 95% CI = 2.38-9.72), and pancreatic (OR = 5.12, 95% CI = 2.43-10.78) cancers, were significantly overexpressed, and miR-19 was tightly related to some clinicopathological characteristics, such as lymph node metastasis (OR = 1.74, 95% CI = 1.05-2.86). Although gastrointestinal cancer patients with low and high miR-19 expression had comparable OS (overall survival) and DFS (disease-free survival), subgroup analyses showed that patients with high miR-19 presented better DFS than those with low miR-19 in liver cancer (HR = 0.46, 95% CI = 0.30-0.71). CONCLUSIONS: miR-19 might be a potential progression and prognostic biomarker for gastrointestinal malignancy.

The Role of Serum Calcium in Assessing Metabolic Syndrome in Colorectal Cancer.

OBJECTIVE: The association of serum calcium with metabolic syndrome in colorectal cancer (CRC) is largely unknown. This study investigated the relationship between serum calcium and patients' clinical characteristics, as well as metabolic parameters in CRC patients. METHODS: CRC patients in Peking University People's Hospital from June 2015 to December 2018 were included; serum calcium, HDL (high-density lipoprotein), LDL (low-density lipoprotein), TC (total cholesterol), TG (triglyceride), FPG (fasting plasma glucose) and albumin were detected. An unpaired t test and covariance analysis were conducted to determine the difference of serum calcium in different groups. Correlation analyses (simple and partial) were carried out to evaluate the association of serum calcium with metabolic parameters. RESULTS: Two hundred and fifteen patients were recruited in the study. CRC patients with distal lesions had higher levels of total and corrected calcium than the proximal lesion group by adjusting for confounders, and patients with small tumor size, as well as with a history of diabetes, exhibited higher total calcium than their counterparts. Significant associations of total calcium with serum glucose and lipids were observed in CRC patients, and the correlation between total calcium and serum lipids was still significant by adjusting for confounders. Corrected calcium showed a significant correlation with LDL and TC but not with FPG, TG or HDL. CONCLUSIONS: Serum calcium, especially total calcium, might be more sensitive than FPG and lipids for metabolic syndrome in CRC patients.

A New Classifier Based on Laboratory Indicators for Early Diagnosis and Prognosis Prediction of Ewing's Sarcoma.

BACKGROUND: Ewing's sarcoma (ES) is a prevalent bone malignancy. It is critical to explore new diagnostic and prognostic indicators because of the rapid progression of ES and the low survival rate of metastatic ES patients. However, few parameters of clinical significance have been found. The aim of this study was to establish a new classifier with clinical laboratory data to help ES detection and prognosis prediction. METHODS: A total of 135 ES patients, 150 healthy individuals, and 228 patients with primary benign bone lesions were included. Logistic regression on clinical laboratory indicators was conducted to establish the classifier, and then the classifier was assessed by drawing the receiver operating characteristic (ROC) curves. Patient survival was evaluated using the Kaplan-Meier method. RESULTS: We established the diagnostic classifier, called Ces, with clinical laboratory indicators to distinguish ES from healthy individuals. Ces showed great diagnostic performance in the test cohort (area under the receiver operating characteristic curve (AUC) 0.95) and could identify early-stage (AUC 0.93) and small-size (AUC 0.95) ES effectively. In addition, the classifier had good ability to differentiate ES from primary benign bone lesions (AUC 0.77 for Ces, AUC 0.83 for Ces + age). Furthermore, Ces was associated with tumor metastasis and event-free survival (EFS) of ES patients and showed better performance than lactate dehydrogenase (LDH) in prognosis prediction. CONCLUSIONS: Our study indicates that Ces has the potential to be a non-invasive biomarker for ES diagnosis and prognosis.

Serum Calcium is a New Indicator to Evaluate Metabolic Syndrome in Hepatocellular Cancer.

BACKGROUND: The role of serum calcium in hepatocellular cancer (HCC) patients with features of metabolic syndrome (MetS) is largely unknown. This study aimed to determine the association of serum calcium with clinical features, and the correlation between serum calcium and metabolic parameters, including serum fasting plasma glucose (FPG) and lipids, in HCC patients. METHODS: The study included 180 HCC patients. Unpaired t-test and covariance analysis were performed to evaluate the distribution of serum calcium among different categorical variables. Simple correlation analyses and partial correlation analyses were conducted to assess the correlations between serum calcium and metabolic parameters. RESULTS: HCC patients with cirrhosis had significantly lower total serum calcium than those without cirrhosis, and patients with distant metastasis had significantly higher corrected calcium than their counterparts after adjusting for confounders. Significant correlations between total calcium and metabolic parameters were observed in HCC patients, and these correlations were still significant after adjusting for cirrhosis and distant metastasis. However, the corrected serum calcium showed no significant correlation with metabolic parameters. CONCLUSIONS: Serum calcium, especially total serum calcium, might be a more sensitive indicator for metabolic syndrome in HCC patients than FPG and lipids.

Novel classifiers with clinical laboratory parameters for early detection of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is one of the most common malignant bone tumors. It is essential to explore early diagnostic indicators with high sensitivity and specificity due to the rapid progression and metastasis of OS and the poor survival of metastatic OS patients. However, a few indicators of diagnostic significance have been described. METHODS: A total of 458 OS patients, 312 healthy individuals, and 228 patients with primary benign bone lesions were included. Logistic regression was performed on 46 clinical laboratory parameters to establish the diagnostic classifiers, which were evaluated by analysis of the receiver operating characteristic (ROC) curves. RESULTS: We established three diagnostic classifiers, called Cos for all ages, Clos for low ages, and Chos for high ages, with clinical laboratory parameters to distinguish OS from healthy individuals. All classifiers showed better diagnostic performances than alkaline phosphatase (ALP) in the independent validation cohort. In addition, these classifiers had better ability than ALP to discriminate OS from primary benign bone lesions. Furthermore, Cos , Clos, and Chos had larger AUC than ALP to identify small-size and early-stage OS and could also detect ALP-negative OS effectively. CONCLUSION: Our study suggests the potential of Cos , Clos , and Chos as non-invasive biomarkers for early OS.

The clinical values of dysregulated DNA methylation and demethylation intermediates in acute lymphoblastic leukemia.

Objectives: DNA methylation is a well-known epigenetic modification, and it can be iteratively oxidized to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Acute lymphoblastic leukemia (ALL) is a severe hematological disease, and it is essential to find out new biomarkers to better diagnose and cure ALL due to the development of chemo-resistance and low cure rate in adult ALL. This study aims to describe the role of global methylation and demethylation intermediates in ALL. Methods: The levels of global methylation and its oxidation products in the peripheral blood (PB) of ALL patients and healthy controls were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Results: In this study, we described that global 5-mC, 5-hmC and 5-fC levels were dysregulated in ALL, and they were associated with clinical characteristics and genetic abnormalities of ALL patients. Interestingly, 5-mC and 5-hmC were closely related to inflammation, and the levels of 5-hmC were inversely correlated with C-Reactive protein (CRP) and ferritin. Finally, 5-mC and 5-hmC were associated with complete remission (CR), and 5-hmC was revealed as an independent prognostic indicator for ALL. Conclusion: This study described a novel role for global methylation and demethylation intermediates in ALL detection and prognosis, and provided new clue to distinguish high-risk patients and improve the curative effect on ALL patients.

Iron chelation inhibits cancer cell growth and modulates global histone methylation status in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and new treatment strategies for CRC are required because of the existing chemotherapy resistance. Iron chelators, which have been used widely for the treatment of iron-overload disease, were reported to exert anti-proliferative effects in cancer. However, the role of iron chelation in CRC was largely unknown. In this study, we found that the iron chelator DFO inhibited CRC cell growth significantly. In addition, the gene expression profile was greatly changed by DFO treatment, and many cell growth-related genes were dysregulated. Further study showed that DFO induced a significant increase in global histone methylation in CRC cells. However, the levels of histone methyltransferases and histone demethylases did not change in response to DFO treatment, implying that the enzymatic activity of these enzymes might be regulated by iron chelation. In conclusion, this study reveals a novel role for DFO in CRC cell growth, and is the first to demonstrate that global histone methylation is modulated by iron chelation in CRC cells.

Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma.

OBJECTIVE: Lysine-specific demethylase 2A (KDM2A), a specific H3K36me1/2 demethylase, has been reported to be closely associated with several types of cancer. In this study, we aimed to investigate the expression and function of KDM2A in colorectal adenocarcinoma. METHODS: A total of 215 colorectal adenocarcinoma specimens were collected, and then subjected to immunohistochemistry assay to evaluate the expression levels of KDM2A, cyclin D1 and other proteins in colorectal adenocarcinoma tissues. Real-time polymerase chain reaction, Western blot, and other molecular biology methods were used to explore the role of KDM2A in colorectal adenocarcinoma cells. RESULTS: In this study, we report that the expression level of KDM2A is high in colorectal adenocarcinoma tissues, and this high expression promotes the proliferation and colony formation of colorectal adenocarcinoma cells, as demonstrated by KDM2A knockdown experiments. In addition, the expression of KDM2A is closely associated with cyclin D1 expression in colorectal adenocarcinoma tissues and cell lines. CONCLUSIONS: Our study reveals a novel role for high-expressed KDM2A in colorectal adenocarcinoma cell growth, and that the expression of KDM2A is associated with that of cyclin D1 in colorectal adenocarcinoma.

Histone deacetylase HDAC1 expression correlates with the progression and prognosis of lung cancer: A meta-analysis.

BACKGROUND: Histone deacetylase 1 (HDAC1) is an important epigenetic factor, and is thought to be associated with the progression and prognosis of some types of cancer. HDAC1 has been reported to be overexpressed in lung cancer, but the correlation between HDAC1 overexpression and the clinical features or prognosis of lung cancer is controversial. In this study, we investigated the potential association between HDAC1 and lung cancer. MATERIALS AND METHODS: Embase, Web of Science, PubMed, and other sources were searched for relevant studies. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (CI) were calculated to evaluate the association of HDAC1 with lung cancer risk. RESULTS: Eight eligible studies were included in the final meta-analysis. We found that HDAC1 mRNA or protein expression was closely associated with the differentiation grade of lung cancer (OR = 2.36, 95% CI = 1.14-4.87, P = .02). In addition, the protein expression level of HDAC1 in squamous cell carcinoma was higher than that in adenocarcinoma (OR = 1.81, 95% CI = 1.13-2.90, P = .01). Finally, HDAC1 mRNA or protein expression was negatively correlated with the overall survival rate of patients with lung cancer (HR = 2.40, 95% CI = 1.48-3.88, P = .0004). CONCLUSION: In this meta-analysis, our results suggest that HDAC1 may serve as a good diagnostic and prognostic marker for lung cancer.

The expression of histone deacetylase HDAC1 correlates with the progression and prognosis of gastrointestinal malignancy.

Gastrointestinal malignancy is a severe public health threat worldwide, and survival for most types of gastrointestinal cancer is very poor. Therefore, finding better cancer biomarkers to diagnose gastrointestinal malignancy and predict patient survival is essential. HDAC1 has been reported to be closely associated with several types of cancer, but the precise role of HDAC1 in gastrointestinal cancer is not clear. Recently, quite a few studies have investigated the correlation between HDAC1 expression and clinical features or prognosis in multiple types of gastrointestinal malignancies, but the results were inconsistent. In this study, we systematically reviewed the association between HDAC1 and gastrointestinal malignancy using meta-analysis methods, and 28 eligible studies were analyzed. We found that the expression level of HDAC1 in gastrointestinal malignancies, especially in colorectal cancer (OR = 10.84, 95% CI = 5.33-22.07, P< 0.00001), was higher than that in noncancerous tissue, and HDAC1 expression was closely associated with some clinical features of gastrointestinal cancer patients, such as tumor stage (OR = 1.62, 95% CI = 1.28-2.05, P < 0.0001) and tumor grade (OR = 1.75, 95% CI = 1.03-2.95, P = 0.04). In addition, we also found that patients with low HDAC1 expression showed better overall survival than those with high HDAC1 expression in gastrointestinal malignancy, especially in gastric cancer (HR = 1.88, 95% CI = 1.14-3.12, P = 0.01). Our results strongly suggest that HDAC1 may serve as a good diagnostic and prognostic marker for gastrointestinal malignancy.

Epigenetic modification of PKMζ rescues aging-related cognitive impairment.

Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue.

Histone modifications in DNA damage response.

DNA damage is a relatively common event in eukaryotic cell and may lead to genetic mutation and even cancer. DNA damage induces cellular responses that enable the cell either to repair the damaged DNA or cope with the damage in an appropriate way. Histone proteins are also the fundamental building blocks of eukaryotic chromatin besides DNA, and many types of post-translational modifications often occur on tails of histones. Although the function of these modifications has remained elusive, there is ever-growing studies suggest that histone modifications play vital roles in several chromatin-based processes, such as DNA damage response. In this review, we will discuss the main histone modifications, and their functions in DNA damage response.