Clocks, cancer, and chronochemotherapy

Science ◽  
2020 ◽  
Vol 371 (6524) ◽  
pp. eabb0738
Author(s):  
Aziz Sancar ◽  
Russell N. Van Gelder
Keyword(s):  
Gene Expression ◽  
Animal Studies ◽  
Time Dependent ◽  
Specific Interactions ◽  
Improved Outcomes ◽  
Circadian Time ◽  
Daily Rhythmicity ◽  
Clinical Potential ◽  
The Relationship ◽  
Oriented Research

The circadian clock coordinates daily rhythmicity of biochemical, physiologic, and behavioral functions in humans. Gene expression, cell division, and DNA repair are modulated by the clock, which gives rise to the hypothesis that clock dysfunction may predispose individuals to cancer. Although the results of many epidemiologic and animal studies are consistent with there being a role for the clock in the genesis and progression of tumors, available data are insufficient to conclude that clock disruption is generally carcinogenic. Similarly, studies have suggested a circadian time-dependent efficacy of chemotherapy, but clinical trials of chronochemotherapy have not demonstrated improved outcomes compared with conventional regimens. Future hypothesis-driven and discovery-oriented research should focus on specific interactions between clock components and carcinogenic mechanisms to realize the full clinical potential of the relationship between clocks and cancer.

Role of macronutrient intake in the epigenetics of obesity

2022 ◽  
Author(s):  
Priyadarshni Patel ◽  
Jeganathan Ramesh Babu ◽  
Xu Wang ◽  
Thangiah Geetha
Keyword(s):  
Gene Expression ◽  
Animal Studies ◽  
Extensive Study ◽  
Epigenetic Alterations ◽  
Lifestyle Choices ◽  
Obesity Genes ◽  
The Relationship ◽  
Diet And Lifestyle

Obesity is caused by a combination of hereditary and environmental factors. Despite extensive study, contemporary through diet, exercise, education, surgery, and pharmacological treatments, no effective long-term solution has been found to this epidemic. Over the last decade, there has been a tremendous advancement in understanding the science of epigenetics, as well as a rise in public interest in learning more about the influence of diet and lifestyle choices on the health of an individual. Without affecting the underlying DNA sequence, epigenetic alterations impact gene expression. Previous animal studies have shown a link between the type of diet and expression or suppression of obesity genes, but there are very few human studies that demonstrate the relationship between dietary intake and obesity gene expression. This review highlights the effects of carbohydrates, lipids, and protein intake from the diet on obesity-related genes.

Plasminogen Depletion during Streptokinase Treatment or Two-Chain Urokinase Incubation Correlates with Decreased Clot Lysability Ex Vivo and In Vitro

1993 ◽  
Vol 70 (06) ◽  
pp. 0998-1004 ◽  
Author(s):  
Páll T Önundarson ◽  
H Magnús Haraldsson ◽  
Lena Bergmann ◽  
Charles W Francis ◽  
Victor J Marder
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Time Dependent ◽  
State Variables ◽  
Thrombolytic Treatment ◽  
Direct Proportion ◽  
Plasmin Activity ◽  
Plasma Exposure ◽  
The Relationship

SummaryThe relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/1. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 ± 8% after 5 min to 21 ± 8% at 10 min and was significantly lower (8 ± 9%, p <0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p <0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.

Dynamic Changes in the Regulation of Energy Balance after Roux-en-Y Gastric Bypass Are Reflected in Time-Dependent Alterations in Liver Gene Expression

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 289-LB
Author(s):  
M. AGOSTINA SANTORO ◽  
JOSEPH BRANCALE ◽  
JILL CARMODY GARRISON ◽  
SRIRAM MACHINENI ◽  
SCOTT A. LAJOIE ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Bypass ◽  
Energy Balance ◽  
Time Dependent ◽  
Dynamic Changes ◽  
Liver Gene

scholarly journals Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1021
Author(s):  
Carla Abrahamian ◽  
Christian Grimm
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Convincing Evidence ◽  
Signaling Cascades ◽  
Cation Channels ◽  
Pore Channel ◽  
Different Types ◽  
Canonical Wnt ◽  
The Relationship

Microphthalmia-associated transcription factor (MITF) is the principal transcription factor regulating pivotal processes in melanoma cell development, growth, survival, proliferation, differentiation and invasion. In recent years, convincing evidence has been provided attesting key roles of endolysosomal cation channels, specifically TPCs and TRPMLs, in cancer, including breast cancer, glioblastoma, bladder cancer, hepatocellular carcinoma and melanoma. In this review, we provide a gene expression profile of these channels in different types of cancers and decipher their roles, in particular the roles of two-pore channel 2 (TPC2) and TRPML1 in melanocytes and melanoma. We specifically discuss the signaling cascades regulating MITF and the relationship between endolysosomal cation channels, MAPK, canonical Wnt/GSK3 pathways and MITF.

scholarly journals Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner

2021 ◽  
Vol 9 (2) ◽  
pp. 255
Author(s):  
Angelo Iacobino ◽  
Giovanni Piccaro ◽  
Manuela Pardini ◽  
Lanfranco Fattorini ◽  
Federico Giannoni
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Physiological State ◽  
Transcriptional Response ◽  
Sos Response ◽  
Resistant Mutant ◽  
Time Dependent ◽  
Dependent Manner ◽  
Gyra Gene ◽  
Drug Concentrations

Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.

scholarly journals Effects of circadian clock and light on melatonin concentration in Hypericum perforatum L. (St. John’s Wort)

2020 ◽  
Vol 61 (1) ◽  
Author(s):  
Ming-Hsiu Chung ◽  
Tzu-Shing Deng
Keyword(s):  
High Performance ◽  
Hypericum Perforatum ◽  
Fresh Weight ◽  
Melatonin Concentration ◽  
Long Day ◽  
Spatiotemporal Regulation ◽  
Circadian Time ◽  
Hypericum Perforatum L ◽  
Pharmaceutical Industries ◽  
Oriented Research

Abstract Background Melatonin acts as a signaling hormone and entraining agent in many organisms. We studied the spatiotemporal regulation and influence of light (photoperiods, intensities, and spectral qualities) on melatonin concentration in the medicinal herb Hypericum perforatum L. Furthermore, melatonin concentrations in the leaves of eight species of the Hypericum genus were compared and analyzed using high-performance liquid chromatography. Results Melatonin concentration was found to be the highest in its flowers and leaves. The leaves exhibited a rhythmic variation in melatonin concentration of approximately 24 h under both light–dark entrained (Zeitgeber time) and constant light [circadian time (CT)] conditions, with melatonin concentration peaking at approximately CT6 in the middle of the subjective day. Melatonin concentration was influenced significantly by not only photoperiods but also applied light’s wavelength and intensity. It was approximately six times higher under long-day conditions (18-h light:6-h dark) than under short-day photoperiods (10-h light:14-h dark) and was the highest (131 μg/g fresh weight [FW]) under treatment with blue light at an intensity of 45 µmol·m2/s of photons. The melatonin concentration of the two examined Hypericum spp., namely H. kouytchense Lev. and H. coris L., were approximately twice that of H. perforatum L. Conclusion Our findings provide first insights on melatonin-related functions and mechanisms in the circadian system of H. perforatum and useful resources for further melatonin-oriented research and possible applications in agriculture and pharmaceutical industries.

scholarly journals Study on the Relationship between the miRNA-centered ceRNA Regulatory Network and Fatigue

2021 ◽  
Author(s):  
Xingzhe Yang ◽  
Feng Li ◽  
Jie Ma ◽  
Yan Liu ◽  
Xuejiao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Hot Spot ◽  
Genetic Research ◽  
Noncoding Rnas ◽  
Messenger Rnas ◽  
Effective Prevention ◽  
Gene Regulatory ◽  
The Relationship

AbstractIn recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.

scholarly journals Development and Application of the Owner-Bird Relationship Scale (OBRS) to Assess the Relation of Humans to Their Pet Birds

2020 ◽  
Vol 7 ◽  
Author(s):  
Anne-Kathrin Burmeister ◽  
Katrin Drasch ◽  
Monika Rinder ◽  
Sebastian Prechsl ◽  
Andrea Peschel ◽  
...  
Keyword(s):  
Quantitative Research ◽  
Animal Studies ◽  
Online Survey ◽  
Major Influence ◽  
Four Dimensions ◽  
Sociological Approach ◽  
Pet Birds ◽  
Human Animal ◽  
Relationship Of ◽  
The Relationship

Only a few birds besides domestic pigeons and poultry can be described as domesticated. Therefore, keeping a pet bird can be challenging, and the human-avian relationship will have a major influence on the quality of this cohabitation. Studies that focus on characterizing the owner-bird relationship generally use adapted cat/dog scales which may not identify its specific features. Following a sociological approach, a concept of human-animal relationship was developed leading to three types of human-animal relationship (impersonal, personal, and close personal). This concept was used to develop a 21-item owner-bird-relationship scale (OBRS). This scale was applied to measure the relationship between pet bird owners (or keepers) (n = 1,444) and their birds in an online survey performed in Germany. Factor analysis revealed that the relationship between owner and bird consisted of four dimensions: the tendency of the owner to anthropomorphize the bird; the social support the bird provides for the owner; the empathy, attentiveness, and respect of the owner toward the bird; and the relationship of the bird toward the owner. More than one quarter of the German bird owners of this sample showed an impersonal, half a personal, and less than a quarter a close personal relationship to their bird. The relationship varied with the socio-demographic characteristics of the owners, such as gender, marital status, and education. This scale supports more comprehensive quantitative research into the human-bird relationship in the broad field of human-animal studies including the psychology and sociology of animals as well as animal welfare and veterinary medicine.

Introduction

2016 ◽  
pp. xvi-22
Author(s):  
Linda Kalof
Keyword(s):  
Public Policy ◽  
Political Theory ◽  
Animal Studies ◽  
Cultural Representations ◽  
Key Issues ◽  
The Relationship ◽  
Animal Question

This chapter introduces the field of animal studies as an interdisciplinary scholarly endeavor to understand the relationship humans have with other animals. That relationship is mapped into five major categories, reflected in the titles of each of the handbook’s five parts: “Animals in the Landscape of Law, Politics and Public Policy”; “Animal Intentionality, Agency, and Reflexive Thinking”; “Animals as Objects in Science, Food, Spectacle and Sport”; “Animals in Cultural Representations”; and “Animals in Ecosystems.” The chapters in each part are summarized and key issues in the “animal question” are explicated. Chapter topics include animals in research, entertainment, law, political theory, public policy, agency, tourism and ecology. Concluding remarks include an appeal for altruistic coexistence for all beings in the earth’s ecosystem.

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