Search

Search Results

15 results found. Results per page: [ 20 ][ 40 ][ 60 ][ 80 ][ 100 ][ 200 ][ 300 ]

Sort by: [ Publication Date ][ Score ]

Year of publication: [ 2025 ][ 2024 ][ 2023 ][ 2022 ][ 2021 ][ 2020 ][ 2019 ][ 2018 ][ 2017 ][ 2016 ][ 2015 ][ 2014 ][ 2013 ][ 2012 ][ 2011 ][ 2010 ][ 2009 ][ Any ]

Direction: [ Desc ][ Asc ]

• Research Paper Volume 13, Issue 24 pp 25694-25716

  Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging

  Relevance score: 9.38383

  Emanuel Barth, Akash Srivastava, Diane Wengerodt, Milan Stojiljkovic, Hubertus Axer, Otto W. Witte, Alexandra Kretz, Manja Marz

  Keywords: aging, circadian clock system, circadian rhythm, inter-species comparison, longevity, RNA-Seq

  Published in Aging on December 19, 2021

  Show abstract
  Hide abstract

  The circadian clock system influences the biology of life by establishing circadian rhythms in organisms, tissues, and cells, thus regulating essential biological processes based on the day/night cycle. Circadian rhythms change over a lifetime due to maturation and aging, and disturbances in the control of the circadian system are associated with several age-related pathologies.

  However, the impact of chronobiology and the circadian system on healthy organ and tissue aging remains largely unknown. Whether aging-related changes of the circadian system’s regulation follow a conserved pattern across different species and tissues, hence representing a common driving force of aging, is unclear.

  Based on a cross-sectional transcriptome analysis covering 329 RNA-Seq libraries, we provide indications that the circadian system is subjected to aging-related gene alterations shared between evolutionarily distinct species, such as Homo sapiens, Mus musculus, Danio rerio, and Nothobranchius furzeri. We discovered differentially expressed genes by comparing tissue-specific transcriptional profiles of mature, aged, and old-age individuals and report on six genes (per2, dec2, cirp, klf10, nfil3, and dbp) of the circadian system, which show conserved aging-related expression patterns in four organs of the species examined. Our results illustrate how the circadian system and aging might influence each other in various tissues over a long lifespan and conceptually complement previous studies tracking short-term diurnal and nocturnal gene expression oscillations.

• Research Paper Volume 13, Issue 23 pp 25153-25179

  A circadian rhythm-related gene signature associated with tumor immunity, cisplatin efficacy, and prognosis in bladder cancer

  Relevance score: 12.1056385

  Ranran Zhou, Xinyu Chen, Jingjing Liang, Qi Chen, Hu Tian, Cheng Yang, Cundong Liu

  Keywords: circadian rhythm, bladder cancer, prognosis, cisplatin, immunity

  Published in Aging on December 3, 2021

  Show abstract
  Hide abstract

  Circadian dysregulation involves malignant tumor initiation and progression, but the understanding of circadian rhythm’s roles in bladder cancer (BCa) remains insufficient. The circadian rhythm-related genes were collected and clustered based on the Cancer Genome Atlas (TCGA), and the clustering was significantly associated with the prognosis and risk clinicopathological features. Through genomic difference analysis and gene pairing, a circadian rhythm-related signature was successfully established. Kaplan-Meier survival analysis and time-dependent receiver operating curves displayed that the prognosis model was a reliable prognosis biomarker both in the training cohort (n = 396, P = 2.687e-10) and external validation cohort (n = 224, P = 1.45e-02). The patients with high risk have high immune infiltration and high expression of immune checkpoint genes, which partly account for the poor prognosis. TIDE algorithm and the validation in IMvigor210 cohort indicated that the risk signature was a promising marker for the immunotherapeutic response. The risk model could also predict the therapeutic response of cisplatin, which was validated in the Genomics of Drug Sensitivity in Cancer database (P = 0.0049), TCGA (P = 0.038), and T24 BCa cells treated with cisplatin. The functional enrichment showed the risk model was significantly correlated with some malignant phenotypes, such as angiogenesis, epithelial-mesenchymal transition, and KRAS signaling pathway. Totally, we proposed a novel circadian rhythm-related signature for prognosis evaluation, which also helped to predict the immune infiltration and cisplatin sensitivity in BCa.

• Editorial Volume 13, Issue 18 pp 21810-21811

  Does chronic jet lag increase risk of cancer?

  Relevance score: 12.335839

  Suliman Khan, Mengzhou Xue, V. Wee Yong

  Keywords: circadian rhythm, glioma, immunity, microglia, transcriptome

  Published in Aging on September 28, 2021

• Editorial Volume 10, Issue 11 pp 3065-3066

  Aging clocks: disrupted circadian rhythms

  Relevance score: 10.659226

  Aiste Steponenaite, Stephany M. Biello, Gurprit S. Lall

  Keywords: aging, circadian rhythm, NMDA, NR2B, glutamate, light, circadian entrainment

  Published in Aging on November 13, 2018

  

  Light input to the circadian clock is impaired through age induced cellular changes in the circadian clock- impacting entrainment of sleep wake rhythms. Light is decoded by the eye; however little changes are seen in the aged eye with respects to input into the circadian clock. In fact, it is the clock itself that displays a decline in its ability to interpret this information, through alterations in glutamatergic signalling via the NMDA receptor; which ultimately result in global physiological desynchronization leading to implications in health and wellbeing.

  
  
  

• Research Paper Volume 8, Issue 4 pp 642-661

  The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

  Relevance score: 12.176882

  Davina Derous, Sharon E. Mitchell, Cara L. Green, Luonan Chen, Jing‐Dong J. Han, Yingchun Wang, Daniel E.L. Promislow, David Lusseau, John R. Speakman, Alex Douglas

  Keywords: calorie restriction, circadian rhythm, hunger, hypothalamus, transcriptomics

  Published in Aging on February 23, 2016

  Show abstract
  Hide abstract

  Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.

  

  Log Fold change of differentially expressed genes in at least one treatment relative to 12 hour ad libitum feeding (12AL). Blue indicates down-regulation and red upregulation relative to 12AL. 10CR, 20CR, 30CR and 40CR refer to 10 %, 20 %, 30 % and 40 % restriction and 24AL to 24h ad libitum feeding.

  
  
  

  

  Significantly differentially regulated biological processes after three months of CR treatment, based on genes altered across CR, visualized as an Enrichment map (Cytoscape). The nodes represent biological processes, and edges represent overlap between genes in these processes. The color of the nodes represents the significance according to the p-value (white: p-value = 0.05, purple: p-value < 0.01). The size of the nodes corresponds to the size of the gene set. The width of edges is based on similarity coefficients (> 0.5) between the nodes, derived from the overlap of the gene sets underlying the processes.

  
  
  

  

  Effect of graded calorie restriction on circulating hormone levels and genes involved in hunger signaling. (A) Genes involved in hunger signaling based on log fold change relative to ad libitum feeding for 12h per day (12AL) and their correlation coefficient with circulating hormone levels. Blue indicates down-regulation and red upregulation relative to 12AL. Purple indicates a negative correlation coefficient and green a positive correlation with circulating hormone levels. 10CR, 20CR, 30CR and 40CR refers to 10 %, 20 %, 30 % and 40 % restriction and 24AL to 24h ad libitum feeding. (B) Expression levels of key hunger genes plotted against circulating hormone levels. Those genes with a significant correlation based on p-value < 0.05 are included in the plot. (C) Overview of key hunger signaling genes correlating with circulating hormone levels. The lines connecting genes and hormones represent correlations and the width of these lines indicates the strength of the correlation coefficient. Green indicates a positive correlation and purple a negative correlation.

  
  
  

  

  The hunger signaling pathway constructed in the IPA program colored according to genes correlating with circulating leptin levels. Red indicates a positive correlation coefficient and green indicates a negative correlation coefficient. Intensity of the color is related to the strength of the correlation.

  
  
  

  

  Effect of graded calorie restriction on circulating hormone levels and genes involved in circadian rhythm. (A) Genes involved in circadian rhythm pathways based on their log fold change relative to ad libitum feeding for 12h per day (12AL) and their correlation coefficient with circulating hormone levels. Blue indicates down-regulation and red upregulation relative to 12AL. Purple indicates a negative correlation coefficient and green a positive correlation with circulating hormone levels. 10CR, 20CR, 30CR and 40CR refers to 10 %, 20 %, 30 % and 40 % restriction and 24AL refers to 24h ad libitum feeding. (B) Expression levels of core clock genes plotted against circulating hormone levels. Those genes with a significant correlation based on p-value < 0.05 are included in the plot. (C) Overview of core clock genes correlating with circulating hormone levels. The lines connecting hormones and genes represent correlations and the width of these lines indicate the strength of the correlation coefficient. Green indicates a positive correlation and purple a negative correlation.

  
  
  

  

  Genes involved in circadian rhythm pathway constructed in the IPA program colored according their correlation with circulating levels of tumor necrosis factor alpha (TNF-α). Red indicates a positive correlation coefficient while green indicates a negative correlation coefficient. Intensity of the color is related to the strength of the correlation.

  
  
  

  

  Prediction effect plots of the linear model with eigenvector values of principle component 1 (representing phenotypic responses) and gene expression levels of key hunger genes. A cut-off value of p-value < 0.05 was used to determine significant relationships in these linear models. Non-significance is indicated by light grey.

  
  
  

  

  Prediction effect plots of the linear model with eigenvector values of principle component 1 (representing phenotypic responses) and gene expression levels of core clock genes. A cut-off value of p-value < 0.05 was used to determine significant relationships in these linear models. Non-significance is indicated by light grey.

  
  
  

• Research Paper Volume 3, Issue 8 pp 794-802

  Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD⁺ oscillation

  Relevance score: 11.60101

  Saurabh Sahar, Veronica Nin, Maria Thereza Barbosa, Eduardo Nunes Chini, Paolo Sassone-Corsi

  Keywords: Circadian Rhythm, Clock, NAD+, CD38, Amino acid metabolism

  Published in Aging on August 31, 2011

  Show abstract
  Hide abstract

  The Intracellular levels of nicotinamide adenine dinucleotide (NAD⁺) are rhythmic and controlled by the circadian clock. However, whether NAD⁺ oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD⁺ hydrolase CD38. We found that rhythmicity of NAD⁺ was altered in the CD38-deficient mice. The high, chronic levels of NAD⁺ results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD⁺ levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD⁺ levels influence the circadian clock.

  

  WT and CD38 KO mice entrained in 12 hr Light - 12 hr Dark (LD) cycles were sacrificed at indicated times and their liver was dissected out. (A) NAD⁺ concentration was measured by a cycling enzymatic assay. *, p<0.05 (WT vs KO ZT7); **, p<0.001 (WT vs KO ZT 15) [n=3 each time point] (B) NADase activity was measured by a flurometric assay. **, p<0.001 (WT vs KO for each time point) [n=3 each time point].

  
  
  

  

  (A) Representative activity records (actograms) of Wild type (CD38^+/+) and CD38 knockout (CD38^-/-) mice are shown in double plotted format. Mice were entrained in 12 hr Light - 12 hr Dark cycles (LD) and then placed in constant darkness (DD) from the light off (ZT12), on day 1. (B) Bar graph representing the period length of WT and CD38-KO mice. Measurement of the free-running period was based on the onset of activity in DD. Data is represented as mean ± S.E. * *, p = 0.008, n= 6, 8. (C) Representative actograms of Wild type (CD38^+/+) and CD38 knockout (CD38^-/-) mice in LD cycle. (D) Bar graph representing % daily locomotor activity in a one-hour period at the indicated ZTs. Data represents mean ± S.E of 10 days of activity. *, p < 0.05; **, p<0.01 compared to the corresponding wild type, n= 6, 8. (E) Representative actograms from wheel running activity of Wild type (CD38^+/+) and CD38 knockout (CD38^-/-) mice in LD cycle. (F) Bar-graph representing total number of wheel rotations per day. Data is represented as mean ± S.E. **, p = 0.008, n= 6, 5.

  
  
  

  

  Mice entrained in 12 hr Light - 12 hr Dark cycles were sacrificed at indicated times and their liver was dissected out.(A) RNA was prepared at indicated times, reverse transcribed, and real-time PCR was performed using primers for Dbp, Per2, Nampt and 18S rRNA. Data is represented as relative levels of indicated gene normalized to 18S rRNA.(B) Same as in (A), except real-time PCR was performed using primers for Asns, Igfbp1, Moxd1 and c -Myc. Data is represented as relative levels of indicated gene normalized to 18S rRNA. *, p<0.05 compared to the corresponding wild type, n= 3 each time point.

  
  
  

  

  Mice Mice were entrained in 12 hr Light - 12 hr Dark cycles and blood was drawn at indicated times. Amino acid levels in plasma were determined as described in Materials and Methods. Amino acids that displayed statistically significant differences in abundance between the wild type and the CD38-KO mice are shown here. *, p<0.05; **, p<0.01 compared to the corresponding wild type, n= 3 each time point.

  
  
  

• Research Paper pp undefined-undefined

  A circadian rhythm-related gene signature for predicting relapse risk and immunotherapeutic effect in prostate adenocarcinoma

  Relevance score: 11.442497

  Jin Liu, Zhao Tan, Shijie Yang, Xinda Song, Wenping Li

  Keywords: circadian rhythm, immune checkpoint inhibitor, prognosis, prostate adenocarcinoma, FBXL22

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Prostate adenocarcinoma (PRAD) represents the most common male carcinoma in developed countries, its high relapse risk contributes to the second-leading cause of cancer-related deaths. Therefore, it is required to develop an effective signature for predicting the relapse risk of PRAD. To identify a circadian rhythm- (CR-) related predictive signature, we analyzed RNA-seq data of patients with prostate adenocarcinoma (PRAD) from the TCGA and GEO cohort. Seven circadian rhythm- (CR-) related genes (FBXL22, MTA1, TP53, RORC, DRD4, PPARGC1A, ZFHX3) were eventually identified to develop a CR-related signature. AUCs for 3-year overall survival were 0.852, 0.856 and 0.944 in the training set, validation set and an external independent test set (GSE70768), respectively. Kaplan-Meier curve analysis showed that the high-risk group has a reduced relapse-free survival (RFS) than the low-risk group in the training set, validation set, and test set, respectively (P < 0.05). We constructed a prognostic nomogram combining the CR-related signature with T staging to precisely estimate relapse risk of PRAD patients. Finally, we observed that the CR-related gene signature was associated with tumor mutation burden, multiple immune checkpoint molecules and microsatellite instability, and thus could predict response to immune checkpoint inhibitors in PRAD. Conclusively, we developed a circadian rhythm-related gene signature for predicting RFS and immunotherapy efficacy in prostate adenocarcinoma.

• Research Paper pp undefined-undefined

  Identification of key circadian rhythm genes in skin aging based on bioinformatics and machine learning

  Relevance score: 11.442497

  Xiao Xiao, Hao Feng, Yangying Liao, Hua Tang, Lan Li, Ke Li, Feng Hu

  Keywords: skin aging, circadian rhythm, immune infiltration, bioinformatics, machine learning

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Skin aging is often accompanied by disruption of circadian rhythm and abnormal expression of circadian rhythm-related genes. In this study, we downloaded skin aging expression datasets from the GEO database and utilized bioinformatics and machine learning methods to explore circadian rhythm genes and pathways involved in skin aging, revealing the pathological and molecular mechanisms of skin aging. Results showed that 39 circadian rhythm-related genes (CRGs) were identified in skin aging, and these CRGs were enriched in signaling pathways such as glucagon signaling pathway, insulin resistance, thyroid hormone signaling pathway, and adipocytokine signaling pathway. Three key skin aging-related CRGs, SIRT1, ARNTL, and ATF4, were identified based on machine learning. Additionally, we found that skin aging was associated with infiltration of immune cells including NK cells activated, Macrophages M1, Mast cells resting, T cells CD4 memory activated, and Macrophages M2, and the expression of the three key skin aging-related CRGs was correlated with these immune cells. Finally, SIRT1, ARNTL, and ATF4 were all down-regulated in skin aging and had a good ability to distinguish young skin tissue from aging skin tissue. In conclusion, three key CRGs, including SIRT1, ARNTL, and ATF4, which are closely related to skin aging, were obtained based on bioinformatics and machine learning technology screening. These three key CRGs were potential risk genes for skin aging and also associated with changes in the immune microenvironment in skin aging. The language used in this paragraph follows the guidelines for scientific writing specified by SCI, making it clear and concise.

• Research Paper pp undefined-undefined

  Effects of resveratrol on in vitro circadian clock gene expression in young and older human adipose-derived progenitor cells

  Relevance score: 10.197243

  Sophie Kapar, Maria F. Pino, Miguel A. Gutierrez-Monreal, Karyn Esser, Lauren M. Sparks, Melissa L. Erickson

  Keywords: circadian clock, circadian rhythm, aging, adipose-derived progenitor cells, resveratrol

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Observational studies in preclinical models demonstrate age-related declines in circadian functions. We hypothesized that age would be associated with declines in function of cell-autonomous circadian clocks in human tissue. Accordingly, we cultured adipose progenitor cells (APCs) from previously collected white-adipose tissue biopsies from abdominal subcutaneous depots of young (Age: 23.4 ± 2.1 yrs) vs. older female participants (Age: 70.6 ± 5.9 yrs). Using an in vitro model, we compared rhythmic gene expression profiles of core clock components, as an indicator of circadian oscillatory function. We observed consistent circadian rhythmicity of core clock components in young and older-APCs. Expression analysis showed increased levels of some components in older-APCs (CLOCK, CRY1, NR1D1) vs. young. We also investigated resveratrol (RSV), a well-known longevity-enhancing effector, for its effects on rhythmic clock gene expression profiles. We found that RSV resulted in gained rhythmicity of some components (CLOCK and CRY), loss of rhythmicity in others (PER2, CRY2), and altered some rhythmic parameters (NR1D1 and NR1D2), consistent in young and older-APCs. The observation of detectable circadian rhythmicity retained in vitro suggests that the oscillatory function of the cell-autonomous core clock in APCs is perserved at this stage of the aging process. RSV impacts core clock gene expression in APCs, implicating its potential as a therapeutic agent for longevity by targeting the core clock.

• Research Paper pp undefined-undefined

  Dysregulated expression of slingshot protein phosphatase 1 (SSH1) disrupts circadian rhythm and WNT signaling associated to hepatocellular carcinoma pathogenesis

  Relevance score: 9.755559

  Shiue-Wei Lai, Yi-Chiao Cheng, Wen-Chien Huang, Vijesh Kumar Yadav, Iat-Hang Fong, Chi-Tai Yeh, Ching-Kuo Yang, Wei-Hwa Lee, Ming-Yao Chen

  Keywords: hepatocellular carcinoma, SSH1, circadian rhythm, WNT/β-catenin signaling, sennoside A therapy

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Growing evidence underscores the circadian rhythm’s essential function in liver stability and disease. Its disruption is progressively linked with metabolic issues, oncogene triggers, and heightened cancer susceptibility. Research points to slingshot protein phosphatase 1 (SSH1), a modulator of cofilin-1 (CFL-1), as instrumental in the reformation of the actin cytoskeleton, thereby impacting the invasiveness of various cancer types. Yet, the dynamics of SSH1’s influence on liver cell stemness and circadian activity remain unclear. Through in-silico, tissue analysis, and functional assays, the study reveals a significant SSH1 expression in HCC samples, compared to non-cancerous counterparts, across six HCC platforms (AUC between 0.62 and 0.77, p < 0.01). The aberrant expression of SSH1 was correlated with poor patients’ survival (HR = 1.70, p = 0.0063) and progression-free (HR = 1.477, p = 0.0187) survival rates. Targeting SSH1, either via Sennoside A or CRISPR SSH1 in Huh7 cells (Huh7-SSH1-/-) significantly suppressed cell viability, migration, invasion, colony and tumorsphere formation of the Huh7-SSH1-/- cells. Mechanistically, we showed that downregulated SSH1 expression suppressed CLOCK, BMAL1, WNT3, β-catenin, LRP5/6, BCL2, VIM and Snail, with concomitant upregulated CFL-1/2, and CRY1 expression, indicating dysregulated circadian rhythm and WNT/β-catenin oncogenic pathway deactivation. Treatments in reflected notable tumor size reductions in the mice treated with SenAlight (1.76-fold, p < 0.01) and SenAdark (3.79-fold, p < 0.01). The expression of SSH1, CLOCK, BMAL1 and β-catenin proteins were significantly downregulated in the SenAlight and SenAdark mice; this was more so in the SenAdark mice. This reveals a potential treatment approach for HCC patients.

• Research Paper pp undefined-undefined

  Circadian rhythm-related factors of PER and CRY family genes function as novel therapeutic targets and prognostic biomarkers in lung adenocarcinoma

  Relevance score: 12.1056385

  Chin-Chou Wang, Wei-Hsun Lin, Su-Chi Ku, Wan-Jou Shen, Hoang Dang Khoa Ta, Gangga Anuraga, Fang-Wen Liu, Chiu-Fan Shen, Shu-He Wang, Chia-Chen Yang, Chih-Yang Wang, Wei-Jan Wang

  Keywords: circadian rhythm, lung adenocarcinoma, biomarker, PER, CRY

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  The period (PER) and cryptochrome (CRY) families play critical roles in circadian rhythms. The imbalance of circadian factors may lead to the occurrence of cancer. Expressions of PER and CRY family members decrease in various cancers. Nevertheless, expression levels, genetic variations, and molecular mechanisms of PER and CRY family members in lung adenocarcinoma (LUAD) and their correlations with prognoses and immune infiltration in LUAD patients are still unclear. In this study, to identify their biological functions in LUAD development, comprehensive high-throughput techniques were applied to analyze the relationships of expressions of PER and CRY family members with genetic variations, molecular mechanisms, and immune infiltration. The present results showed that transcription levels of PER1 and CRY2 in LUAD were significantly downregulated. High expression levels of PER2, PER3, CRY1, and CRY2 indicated longer overall survival. Some cancer signaling pathways were related to PER and CRY family members, such as cell-cycle, histidine metabolism, and progesterone-mediated oocyte maturation pathways. Expressions of PER and CRY family members significantly affected the infiltration of different immune cells. In conclusion, our findings may help better understand the molecular basis of LUAD, and provide new perspectives of PER and CRY family members as novel biomarkers for LUAD.

• Research Paper pp undefined-undefined

  A circadian rhythm-related biomarker for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma

  Relevance score: 11.016993

  Yuanjun Cheng, Jie Yao, Qianru Fang, Bin Chen, Guohui Zang

  Keywords: circadian rhythm, immune checkpoint inhibitor, prognosis, lung adenocarcinoma, BARX2

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Lung adenocarcinoma (LUAD) remains a major reason of cancer-associated mortality globally, and there exists a lack of indicators for survival in LUAD patients. Therefore, it is clinically required to obtain a novel prognostically indicator for guiding clinical management. In this study, we established a circadian rhythm (CR) related signature by a combinative investigation of multiple datasets. The newly-established signature showed an acceptable ability to predict survival and could serve as an independent indicator for prognosis. Moreover, the newly-established signature was critically associated with tumor malignancy, including proliferation, invasion, EMT and metastasis. The newly-established signature was predictive of response to immune checkpoint blockade. Collectively, we established a CR-related gene signature that could forecast survival, tumor malignancy and therapeutic response; our findings could help guiding clinical management.

• Research Paper pp undefined-undefined

  Identification of a circadian-based prognostic signature predicting cancer-associated fibroblasts infiltration and immunotherapy response in bladder cancer

  Relevance score: 10.542935

  Li Zhou, Jiaming He, Zhiming Hu, Hongwei Li, Jinlong Li

  Keywords: bladder cancer, circadian rhythm, cancer-associated fibroblasts, prognostic model, immunotherapy

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Circadian rhythm disruption impacts the efficiency of both chemotherapy and immunotherapy, yet identifying the key factors involved remains challenging. Circadian rhythm disruption can trigger aberrant fibroblasts activation, suggesting potential roles of cancer-associated fibroblasts (CAFs) in addressing this issue. In this paper, TCGA-BLCA patients were classified into two subgroups based on the expression of core circadian rhythm genes (CCRGs). The CCRG-based subgroups showed distinct fibroblast-related signals, from which a risk model composed of five fibroblast-related genes was finally established with excellent survival prognostic value in both TCGA and GEO datasets. The risk model was positively associated with the infiltration of CAFs and can efficiently predict the immunotherapy response in BLCA. Besides, high-risk score was associated with reduced sensitivity to a majority of traditional chemotherapeutic drugs such as Oxaliplatin and Gemcitabine. Further, the correlation between CCRGs and the risk genes was analyzed. Among the five risk genes, FAM20C displayed the most extensive correlation with the CCRGs and exhibited the strongest connection with CAFs infiltration. Moreover, FAM20C independently served as a predictor for the response to immunotherapy in BLCA. In conclusions, this study has identified a circadian-based signature for evaluating CAFs infiltration and predicting the efficacy of chemotherapy and immunotherapy. The central gene FAM20C has emerged as a promising candidate merits further investigations.

• Research Paper pp undefined-undefined

  Mining key circadian biomarkers for major depressive disorder by integrating bioinformatics and machine learning

  Relevance score: 10.218399

  Yuhe Shi, Jue Zhu, Chaowen Hou, Xiaoling Li, Qiaozhen Tong

  Keywords: major depressive disorder, circadian rhythm, bioinformatics, machine learning, biomarker, immune infiltration, drug prediction

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Objective: This study aimed to identify key clock genes closely associated with major depressive disorder (MDD) using bioinformatics and machine learning approaches.

  Methods: Gene expression data of 128 MDD patients and 64 healthy controls from blood samples were obtained. Differentially expressed were identified and weighted gene co-expression network analysis (WGCNA) was first performed to screen MDD-related key genes. These genes were then intersected with 1475 known circadian rhythm genes to identify circadian rhythm genes associated with MDD. Finally, multiple machine learning algorithms were applied for further selection, to determine the most critical 4 circadian rhythm biomarkers.

  Results: Four key circadian rhythm genes (ABCC2, APP, HK2 and RORA) were identified that could effectively distinguish MDD samples from controls. These genes were significantly enriched in circadian pathways and showed strong correlations with immune cell infiltration. Drug target prediction suggested that small molecules like melatonin and escitalopram may target these circadian rhythm proteins.

  Conclusion: This study revealed discovered 4 key circadian rhythm genes closely associated with MDD, which may serve as diagnostic biomarkers and therapeutic targets. The findings highlight the important roles of circadian disruptions in the pathogenesis of MDD, providing new insights for precision diagnosis and targeted treatment of MDD.

• Research Paper pp undefined-undefined

  Identifying novel circadian rhythm biomarkers for diagnosis and prognosis of melanoma by an integrated bioinformatics and machine learning approach

  Relevance score: 12.07206

  Yi Xu, Churuo Zeng, Jie Bin, Hua Tang, Wei Li

  Keywords: melanoma, circadian rhythm, biomarker, prognostic model, bioinformatics, machine learning

  Published in Aging on Invalid Date

  Show abstract
  Hide abstract

  Melanoma is a highly malignant skin tumor with poor prognosis. Circadian rhythm is closely related to melanoma pathogenesis. This study aimed to identify key circadian rhythm genes (CRGs) in melanoma and explore their potential as diagnostic and prognostic biomarkers. Microarray data of melanoma tissues and normal skins were obtained. Differentially expressed genes were identified and weighted gene co-expression network analysis (WGCNA) was performed to screen hub genes associated with melanoma. By overlapping hub genes with known CRGs, 125 melanoma-related CRGs were identified. Functional enrichment analysis revealed these CRGs were mainly involved in circadian rhythm and other cancer-related pathways. Three machine learning algorithms including LASSO regression, support vector machine-recursive feature elimination (SVM-RFE), and random forest were utilized to select key CRGs. Six CRGs (ABCC2, CA14, EGR3, FBXW7, LDHB, and PSEN2) were identified as key CRGs for melanoma diagnosis and prognosis. Diagnostic values of key CRGs were evaluated by ROC analysis in training and validation sets. Prognostic values of key CRGs were assessed by survival analysis and a multivariate Cox regression prognostic model was constructed. The prognostic model could effectively stratify melanoma patients into high- and low-risk groups with significantly different survival. A nomogram integrating clinical variables and risk score was built to predict 3-, 5- and 10-year overall survival of melanoma patients. In summary, six CRGs were identified as key genes associated with melanoma pathogenesis and may serve as promising diagnostic and prognostic biomarkers. The prognostic model and nomogram could facilitate personalized prognosis evaluation of melanoma patients.