Non-Hereditary Obesity Type Networks and New Drug Targets: An In Silico Approach.

Obesity, a chronic, preventable disease, has significant comorbidities that are associated with a great human and financial cost for society. The aim of the present work is to reconstruct the interactomes of non-hereditary obesity to highlight recent advances of its pathogenesis, and discover potential therapeutic targets. Obesity and biological-clock-related genes and/or gene products were extracted from the biomedical literature databases PubMed, GeneCards and OMIM. Their interactions were investigated using STRING v11.0 (a database of known and predicted physical and indirect associations among genes/proteins), and a high confidence interaction score of >0.7 was set. We also applied virtual screening to discover natural compounds targeting obesity- and circadian-clock-associated proteins. Two updated and comprehensive interactomes, the (a) stress- and (b) inflammation-induced obesidomes involving 85 and 93 gene/gene products of known and/or predicted interactions with an average node degree of 9.41 and 10.8, respectively, were produced. Moreover, 15 of these were common between the two non-hereditary entities, namely, ADIPOQ, ADRB2/3, CCK, CRH, CXCL8, FOS, GCG, GNRH1, IGF1, INS, LEP, MC4R, NPY and POMC, while phelligridin E, a natural product, may function as a potent FOX1-DBD interaction blocker. Molecular networks may contribute to the understanding of the integrated regulation of energy balance/obesity pathogenesis and may associate chronopharmacology schemes with natural products.

Contact allergy caused by acrylates in nail cosmetics: A pilot study from Greece.

BACKGROUND: The growing popularity of nail techniques based on acrylates has led to a higher frequency of sensitization in both nail technicians and users. OBJECTIVES: The study aimed to assess cases of allergic contact dermatitis (ACD) caused by acrylates in individuals with occupational or non-occupational exposure to nail techniques. METHODS: A preliminary study was conducted on 30 patients with ACD caused by acrylates in nail techniques, who were patch tested from September 2022 to March 2023 at the First Department of Dermatology and Venereology of Andreas Syggros Hospital, Athens, Greece. RESULTS: Thirty female patients with ACD to acrylates were documented (15 users and 15 nail technicians and users). The most common allergens were: 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl methacrylate (HPMA) and ethyleneglycol dimethacrylate (EGDMA), which tested positive in all 30 patients (100.0%). Twenty patients (66.7%) had been exposed to dental procedures involving acrylates, before the onset of ACD. Nail technicians exhibited extensive skin lesions, 40.0% experienced ACD within the first year of work and 13.3% during their professional practice. Three of them (20.0%) had to discontinue their work. CONCLUSION: Acrylates have been identified as potent allergens, necessitating the implementation of safety measures for the use of these chemicals in nail techniques.

Diet and metabolism are back: The oldest known Islamic medical manuscript bridges the gap from ancient to modern gout management.

Gout is a chronic disease frequently associated with lifestyle; its prevalence is increasing in Western societies, as well as in the Middle East. Apart from its partial genetic features, diet accounts for 12% of the causality of the disease, while purine-rich foods contribute decisively to its development and evaluation. The influential Persian physician of the medieval ages, Abu Bakr Muhammad Ibn Zakariya al-Razi (or by his Latin name Rhazes; 860-925 AD), wrote a short book (20 chapters) entitled 'Treatise on gout'. Rhazes adopted the Hippocratic humoralism, and suggested that the disease results from metabolic excess in the peripheral blood, presenting sex dimorphism and age-dependence. His therapeutic guidelines include a diet prescribed by a physician, the use of laxatives and emetics, counter-balancing excess or deficiency of bile or phlegm and analgesics, bloodletting, foot and steam baths, as well as salves and poultices as preventive measures. He appends differential dietary restrictions/suggestions for phlegmatic or choleric patients: Small rations and intake of good quality foods low in purine by 20% for phlegmatic and 28% for choleric patients, as well as the restriction of foods high in purine by 27% for phlegmatic and 22% for the choleric patients. Finally, the acidic to alkaloid food intake ratio suggested is 2/5 for choleric and 3/7 for phlegmatic patients. His suggested foods and drugs are vitamin C and B-rich complexes, thereby inhibiting the accumulation of tophi.

Octenidine Versus Dispase Gels for Wound Healing After Cryosurgery Treatment in Patients with Basal Cell Carcinoma.

For a specific group of patients with basal cell carcinoma (small, low risk), cryosurgery could be the suggested treatment, which results in the formation of an ulcer in the lesion area. The proteolytic enzymes' contribution to the wound healing is an ongoing research goal. Preclinical animal experiments in the Laboratory of the Pharmaceutical Technology Department of the National and Kapodistrian University of Athens have showed that a dose of 5 U/mL of dispase gel after the formation of tissue rashes, significantly promoted wound healing. Herein, a feasibility study in 16 patients enrolled by the First Department of Dermatology of Andreas Syggros Hospital was designed: 5 U/mL of dispase gel (once every 3 days) versus a drug reference containing octenidine (daily administration). The evaluation of the healing effect, safety, and tolerance was done on days 1 (cryosurgery), 2, 7, 21, and 60. The study end point was considered either the ulcer complete healing or the eighth week since treatment initiation. Wound healing was faster with dispase gel and hemoglobin reduced rapidly after the seventh day. Yet, hydration was higher in the control group. Our non-parametric analysis provides evidence that the dispase gel shows faster healing compared to the reference drug, in humans, meriting further investigation in larger human sample sizes before massive production of the product.

Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.

Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.

Simultaneous Multiple-Stages Mpox Genital Lesions on the Same Site in a Traveler to Greece: A Case Report.

A 47-year-old Caucasian traveller from an mpox (formerly monkeypox and also best suited abbreviated MPX)-endemic country was referred for a skin rash, of recent onset, confined to the genital area. The rash consisted of erythematous umbilicated papules, vesicles and pustules with a characteristic white ring. The lesions were observed simultaneously at different stages of progression on the same anatomical site, a clinical presentation that is not encountered frequently. The patient was febrile, fatigued and had blood-tinged cough. The clinical suspicion of mpox was raised, and the initial real-time PCR identified a non-variola orthopox virus, which was confirmed at the National Reference Laboratory to belong to the West African clade.

Tissue and Serum Biomarkers in Degenerative Aortic Stenosis-Insights into Pathogenesis, Prevention and Therapy.

BACKGROUND AND AIM: Degenerative Aortic Stenosis (DAS) is a common disease that causes substantial morbidity and mortality worldwide, especially in the older population. Our aim was to further investigate novel serum and tissue biomarkers to elucidate biological processes involved in this entity. MATERIAL AND METHODS: We evaluated the expression of six biomarkers significantly involved in cardiovascular pathology, i.e., irisin, periostin, osteoglycin, interleukin 18, high mobility group box 1 and proprotein convertase subtilisin/kexin type 9 in the serum at the protein level, and in the tissue at both the protein and mRNA levels of patients with AS (N = 60). Five normal valves obtained after transplantation from hearts of patients with idiopathic dilated cardiomyopathy were also studied. Serum measurements were also performed in 22 individuals without valvular disease who served as controls (C). RESULTS: Higher levels of all factors were found in DAS patients' serum than in normal C. IHC and PCR mRNA tissue analysis showed the presence of all biomarkers in the aortic valve cusps with DAS, but no trace of PCR mRNA was found in the five transplantation valves. Moreover, periostin serum levels correlated significantly with IHC and mRNA tissue levels in AS patients. CONCLUSION: We showed that six widely prevalent biomarkers affecting the atherosclerotic process were also involved in DAS, suggesting a strong osteogenic and pro-inflammatory profile, indicating that aortic valve calcification is a multifactorial biological process.

Neuroendocrine System Adaptation during Consecutive Extrinsic Stimuli: A Pilot Dynamic Study.

This pilot repeated measures study aims to evaluate the dynamics of the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis, and/or their interplay with low-level inflammation in healthy schoolchildren during consecutive extrinsic stimuli. Twenty healthy schoolchildren and adolescents aged 11-14 years (12.5 ± 1.5) were consecutively exposed to an oral task (#2) and an arithmetic task (#3) (Trier Social Stress Test for Children (TSST-C)), lasting 5 min each, and a three-minute cellular phone call (#4). Salivary cortisol (SC) was sampled at baseline (#1) and immediately after each exposure (#2, 3, and 4). Baseline serum high-sensitivity C-reactive protein (hsCRP) and cortisol levels were also assessed. ANS dynamics and complexity were measured using Sample Entropy (SampEn) at each experimental time period (#1-4). Baseline serum hCRP and cortisol correlated negatively to each other, while the ANS and HPA axis acute reactions to the three consecutive stimuli differed over time. The ANS adaptation to these stimuli included complexity modulation, which was not dependent on baseline hsCRP or cortisol, and weakened during the third stimulation. However, baseline hsCRP and cortisol had a weakening and an increasing effect on the HPA axis over time, respectively. We conclude that low-level inflammation and baseline morning cortisol level have no effect on ANS dynamics but influence the HPA axis response to consecutive external stimuli.

Clinical differences between early-onset and mid-and-late-onset Parkinson's disease: Data analysis of the Hellenic Biobank of Parkinson's disease.

BACKGROUND: Age at onset is one of the most critical factors contributing to the clinical heterogeneity of Parkinson's disease (PD), and available evidence is rather conflicting. OBJECTIVE: The aim of this study is to investigate the clinical differences between early-onset PD (EOPD) and mid-and-late-onset PD (MLOPD) in the Greek population, based on the existing data of the Hellenic Biobank of PD (HBPD). METHODS: HBPD contains information of PD cases from two centers in Greece during 2006-2017. Patients with the A53T mutation in the SNCA gene or mutations in the GBA1 gene were excluded. Associations between clinical characteristics (motor and non-motor symptoms, side of onset, first symptom, motor complications) and MLOPD versus EOPD were explored with a single logistic regression model adjusting for gender, family history of PD, disease and dopaminergic therapy duration, disease severity (UPDRS III), levodopa equivalent daily dose, as well as each of the other clinical characteristics. RESULTS: 675 patients (129 EOPD, 546 MLOPD) were included. EOPD was more frequently associated with dystonia (OR 0.19, 95% CI 0.08-0.50, p < 0.01) and motor complications (0.23, 0.07-0.76, 0.02), compared to MLOPD. Bilateral onset (9.38, 1.05-84.04, 0.045) and autonomic dysfunction (2.31, 1.04-5.11, 0.04) were more frequently associated with MLOPD. CONCLUSIONS: EOPD and MLOPD display distinct clinical profiles, regarding motor and non-motor symptoms, side of onset and motor complications in the Greek population. These differences may reflect diverse pathophysiological backgrounds, potentially attributed to genetic or age-related epigenetic influences.

Hypertension Predisposition and Thermoregulation Delays in Adolescents with Polycystic Ovary Syndrome: A Pilot Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder in which clinical, sonographic, and endophenotypic features have been underinvestigated or inconclusive, especially in the early stages of the disease (adolescence/young adulthood). OBJECTIVE: This prospective pilot study focused on the differences of multiple physiological functions between Greek adolescent/young adult females suffering from PCOS and age- and body mass index (BMI)- matched healthy controls. STUDY DESIGN: Nineteen PCOS patients and eighteen healthy controls (aged 13 to 23 years) were studied for: (i) biochemical and hormonal dysfunction by measuring circulating glucose, insulin, and androgen levels; (ii) arterial stiffness with pulse wave analysis (PWA) by Sphygmocord; (iii) intima-media thickness (IMT) by ultrasound; (iv) heart rate variability (HRV) by Task Force Monitor; and (v) QT, QRS, QT, P, QRSD by electrocardiogram (ECG). Statistical analysis included Hedge's g correction for small samples bias, and the results are shown using the Hedge's g effect size and 95% CI, in line with precision medicine prerequisites. RESULTS: Significant differences in pulse wave velocity (PWV) (g = 0.964 [0.296, 1.632]), subendocardial viability ratio (SEVR) carotid (g = -0.679 [-1.329, -0.030]), pulse pressure (PP) carotid (g = 0.942 [0.275, 1.608]), systolic pressure (SP) carotid (g = 0.785 [0.129, 1.440]), free-testosterone (g = 0.677 [0.042, 0.312]), and Delta4-androstenedione (g = 0.735 [0.097, 0.373]) were observed between PCOS patients and controls. No differences were detected in the remaining endocrine and PWA or ECG biomarkers. CONCLUSIONS: Our multidisciplinary approach showed early onset of vascular dysfunction, predisposition to hypertension, thermoregulation delays, and metabolic syndrome changes in adolescent/young adult PCOS.

Thrombocytopenia in COVID­19 and vaccine­induced thrombotic thrombocytopenia.

The highly heterogeneous symptomatology and unpredictable progress of COVID­19 triggered unprecedented intensive biomedical research and a number of clinical research projects. Although the pathophysiology of the disease is being progressively clarified, its complexity remains vast. Moreover, some extremely infrequent cases of thrombotic thrombocytopenia following vaccination against SARS­CoV­2 infection have been observed. The present study aimed to map the signaling pathways of thrombocytopenia implicated in COVID­19, as well as in vaccine­induced thrombotic thrombocytopenia (VITT). The biomedical literature database, MEDLINE/PubMed, was thoroughly searched using artificial intelligence techniques for the semantic relations among the top 50 similar words (>0.9) implicated in COVID­19­mediated human infection or VITT. Additionally, STRING, a database of primary and predicted associations among genes and proteins (collected from diverse resources, such as documented pathway knowledge, high­throughput experimental studies, cross­species extrapolated information, automated text mining results, computationally predicted interactions, etc.), was employed, with the confidence threshold set at 0.7. In addition, two interactomes were constructed: i) A network including 119 and 56 nodes relevant to COVID­19 and thrombocytopenia, respectively; and ii) a second network containing 60 nodes relevant to VITT. Although thrombocytopenia is a dominant morbidity in both entities, three nodes were observed that corresponded to genes (AURKA, CD46 and CD19) expressed only in VITT, whilst ADAM10, CDC20, SHC1 and STXBP2 are silenced in VITT, but are commonly expressed in both COVID­19 and thrombocytopenia. The calculated average node degree was immense (11.9 in COVID­19 and 6.43 in VITT), illustrating the complexity of COVID­19 and VITT pathologies and confirming the importance of cytokines, as well as of pathways activated following hypoxic events. In addition, PYCARD, NLP3 and P2RX7 are key potential therapeutic targets for all three morbid entities, meriting further research. This interactome was based on wild­type genes, revealing the predisposition of the body to hypoxia­induced thrombosis, leading to the acute COVID­19 phenotype, the 'long­COVID syndrome', and/or VITT. Thus, common nodes appear to be key players in illness prevention, progression and treatment.

A Counterintuitive Neutrophil-Mediated Pattern in COVID-19 Patients Revealed through Transcriptomics Analysis.

The COVID-19 pandemic has persisted for almost three years. However, the mechanisms linked to the SARS-CoV-2 effect on tissues and disease severity have not been fully elucidated. Since the onset of the pandemic, a plethora of high-throughput data related to the host transcriptional response to SARS-CoV-2 infections has been generated. To this end, the aim of this study was to assess the effect of SARS-CoV-2 infections on circulating and organ tissue immune responses. We profited from the publicly accessible gene expression data of the blood and soft tissues by employing an integrated computational methodology, including bioinformatics, machine learning, and natural language processing in the relevant transcriptomics data. COVID-19 pathophysiology and severity have mainly been associated with macrophage-elicited responses and a characteristic "cytokine storm". Our counterintuitive findings suggested that the COVID-19 pathogenesis could also be mediated through neutrophil abundance and an exacerbated suppression of the immune system, leading eventually to uncontrolled viral dissemination and host cytotoxicity. The findings of this study elucidated new physiological functions of neutrophils, as well as tentative pathways to be explored in asymptomatic-, ethnicity- and locality-, or staging-associated studies.

Emotional Analysis of Twitter Posts During the First Phase of the COVID-19 Pandemic in Greece: Infoveillance Study.

BACKGROUND: The effectiveness of public health measures depends upon a community's compliance as well as on its positive or negative emotions. OBJECTIVE: The purpose of this study was to perform an analysis of the expressed emotions in English tweets by Greek Twitter users during the first phase of the COVID-19 pandemic in Greece. METHODS: The period of this study was from January 25, 2020 to June 30, 2020. Data collection was performed by using appropriate search words with the filter-streaming application programming interface of Twitter. The emotional analysis of the tweets that satisfied the inclusion criteria was achieved using a deep learning approach that performs better by utilizing recurrent neural networks on sequences of characters. Emotional epidemiology tools such as the 6 basic emotions, that is, joy, sadness, disgust, fear, surprise, and anger based on the Paul Ekman classification were adopted. RESULTS: The most frequent emotion that was detected in the tweets was "surprise" at the emerging contagion, while the imposed isolation resulted mostly in "anger" (odds ratio 2.108, 95% CI 0.986-4.506). Although the Greeks felt rather safe during the first phase of the COVID-19 pandemic, their positive and negative emotions reflected a masked "flight or fight" or "fear versus anger" response to the contagion. CONCLUSIONS: The findings of our study show that emotional analysis emerges as a valid tool for epidemiology evaluations, design, and public health strategy and surveillance.

Interactions Networks for Primary Heart Sarcomas.

Personalized medicine incorporates genetic information into medical practice so as to optimize the management of chronic diseases. In rare diseases, such as heart cancer (incidence 0.0017-0.33%), this may be elusive. Ninety-five percent of the cases are due to secondary involvementwith the neoplasm originating in the lungs, breasts, kidney, blood, or skin. The clinical manifestations of heart tumors (benign or malignant) include heart failure, hypertension, and cardiac arrhythmias of varying severity, frequently resulting in blood vessel emboli, including strokes. This study aims to explain the pathophysiology and contribute to a P4 medicine model for use by cardiologists, pathologists, and oncologists. We created six gene/protein heart-related and tumor-related targets high-confidence interactomes, which unfold the main pathways that may lead to cardiac diseases (heart failure, hypertension, coronary artery disease, arrhythmias), i.e., the sympathetic nervous system, the renin-angiotensin-aldosterone axis and the endothelin pathway, and excludes others, such as the K oxidase or cytochrome P450 pathways. We concluded that heart cancer patients could be affected by beta-adrenergic blockers, ACE inhibitors, QT-prolonging antiarrhythmic drugs, antibiotics, and antipsychotics. Interactomes may elucidate unknown pathways, adding to patient/survivor wellness during/after chemo- and/or radio-therapy.

Polycystic οvary syndrome revisited: An interactions network approach.

BACKGROUND: The polycystic ovary syndrome (PCOS) has genetic, epigenetic, metabolic and reproductive aspects, while its complex pathophysiology has not been conclusively deciphered. AIM: The goal of this research was to screen the gene/gene products associated with PCOS and to predict any possible interactions with the highest possible fidelity. MATERIALS AND METHODS: STRING v10.5 database and a confidence level of 0.7 were used. RESULTS: A highly interconnected network of 48 nodes was created, where insulin (INS) appears to be the major hub. INS upstream and downstream defects were analysed and revealed that only the kisspeptin- and glucagon-coding genes were upstream of INS. CONCLUSION: A metabolic dominance was inferred and discussed herein with its implications in puberty, obesity, infertility and cardiovascular function. This study, thus, may contribute to the resolution of a scientific conflict between the USA and EU definitions of the syndrome and/or provide a new P4 medicine approach.

COVID-19-Induced Fear in Infoveillance Studies: Pilot Meta-analysis Study of Preliminary Results.

BACKGROUND: The World Health Organization named the phenomenon of misinformation spread through social media as an "infodemic" and recognized the need to curb it. Misinformation infodemics undermine not only population safety but also compliance to the suggestions and prophylactic measures recommended during pandemics. OBJECTIVE: The aim of this pilot study is to review the impact of social media on general population fear in "infoveillance" studies during the COVID-19 pandemic. METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol was followed, and 6 out of 20 studies were retrieved, meta-analyzed, and had their findings presented in the form of a forest plot. RESULTS: The summary random and significant event rate was 0.298 (95% CI 0.213-0.400), suggesting that social media-circulated misinformation related to COVID-19 triggered public fear and other psychological manifestations. These findings merit special attention by public health authorities. CONCLUSIONS: Infodemiology and infoveillance are valid tools in the hands of epidemiologists to help prevent dissemination of false information, which has potentially damaging effects.

Adults' Stress Response to Unexpected Oral and Arithmetic Tasks in Supine Position.

To study the autonomic nervous system (ANS) and hypothalamus pituitary adrenal axis (HPA) response before and after mental stress test in healthy adolescents and adults, is the aim of this study. Twenty healthy adults (aged 23-46 years) entered the Trier Social Stress Test (TSST), after informed consent signing. The procedure was modified: (a) the participants' position was supine as ANS system changes were to be assessed, (b) the interviewers were entering and departing from the session room. Salivary cortisol (marker of HPA axis response) samples were collected at the end of the baseline and 20 min after TSST. ANS of the heart was measured with CNS Task Force Monitor in supine position and was recorded during relaxation (15 min) and after TSST. The sympathovagal balance (LF/HF ratio) for each phase was computed. Evaluations were conducted with R. The HPA axis disturbance between baseline and 20 min after TSST was significant (g = 0.545 [0.092, 0.999]) and in adolescents (whereas, the mean intervals of the sinus rhythm RR parameter were found largely changed (g = 0.834 [0.340, 1.327]). The sympathovagal balance component of heart rate variability LF/HF ratio was founded unchanged (g = 0.215 [-0.211, 0.641]). RR changes were not correlated to salivary cortisol concentrations at any phase. Mean RRIs and salivary cortisol levels were significantly increased, although HPA axis showed medium size effect. However, the systems effectively counterbalance the perturbation, since the LF/HF ratio does not change. Our findings suggest further research in stress effect on HPA and ANS cross-talk and dynamics.

Systems Approaches in the Common Metabolomics in Acute Lymphoblastic Leukemia and Rhabdomyosarcoma Cells: A Computational Approach.

Acute lymphoblastic leukemia is the most common childhood malignancy. Rhabdomyosarcoma, on the other hand, is a rare type of malignancy which belongs to the primitive neuroectodermal family of tumors. The aim of the present study was to use computational methods in order to examine the similarities and differences of the two different tumors using two cell lines as a model, the T-cell acute lymphoblastic leukemia CCRF-CEM and rhabdomyosarcoma TE-671, and, in particular, similarities of the metabolic pathways utilized by two different cell types in vitro. Both cell lines were studied using microarray technology. Differential expression profile has revealed genes with similar expression, suggesting that there are common mechanisms between the two cell types, where some of these mechanisms are preserved from their ancestor embryonic cells. Expression of identified species was modeled using known functions, in order to find common patterns in metabolism-related mechanisms. Species expression manifested very interesting dynamics, and we were able to model the system with elliptical/helical functions. We discuss the results of our analysis in the context of the commonly occurring genes between the two cell lines and the respective participating pathways as far as extracellular signaling and cell cycle regulation/proliferation are concerned. In the present study, we have developed a methodology, which was able to unravel some of the underlying dynamics of the metabolism-related species of two different cell types. Such approaches could prove useful in understanding the mechanisms of tumor ontogenesis, progression, and proliferation.

Bioinformatics Analyses of Spatial Peripheral Circadian Clock-Mediated Gene Expression of Glucocorticoid Receptor-Related Genes.

Glucocorticoids are ubiquitous, pleotropic steroid hormones secreted from the cortices of the adrenal glands in a circadian fashion under the strong influence of the central Clock center located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In previous work, we reported that the circadian transcription factor CLOCK and its heterodimer partner BMAL1 suppress the transcriptional activity of the glucocorticoid receptor (GR) by acetylating a lysine cluster located in its hinge region between the DNA- and ligand-binding domains. This regulation of GR transcriptional activity by CLOCK/BMAL1 functions as a counter-regulatory loop against the diurnally fluctuating circulating glucocorticoids. Here, we have performed further analyses of our data using bioinformatics and computational methods. Gene expression data were analyzed using unsupervised machine learning methods, such as hierarchical clustering, k-means, Naïve Bayes classification, and polynomial regression analyses. We determined expression patterns of Clock-related genes, unraveled the dynamics of spatial data, and defined the temporal function of Clock-mediated GR-regulated genes. Gene expressions manifested nonlinear dynamics, possibly because we obtained dynamic results from stationary measurements. The mechanics of the circadian rhythms are still obscure, and more studies are required to understand how such rhythms influence mammalian physiology.