Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) play crucial role in the regulation of drug metabolizing enzymes and in many essential physiological processes. Cellular signaling by these receptors shares several functional and regulatory features. Here we investigated regulatory cross-talk between these two receptors. Human hepatoma cells (HepG2) were the model of choice. We analyzed the effects of dexamethasone (DEX) and dioxin (TCDD) on i) expression of AhR and GRalpha mRNAs; ii) levels of AhR and GR proteins; iii) transcriptional activities of AhR and GR in reporter assays; iv) 7-ethoxyresorufin-O-deethylase activity (EROD). We found that both DEX and TCDD affected AhR and GR mRNAs expression, proteins levels and transcriptional activities in HepG2 cells. These effects on cellular signaling by AhR and GR comprised up-/down-regulation of gene expression and ligand-dependent protein degradation. We conclude that interactive regulatory cross-talk between GR and AhR receptors in HepG2 cells defines possible implications in physiology and drug metabolism. Future research should be focused on the investigation of AhR-GR cross-talk in various normal human cells and tissues both in vitro and in vivo.

• MeSH
• Cytochrome P-450 CYP1A1 metabolism   MeSH
• Dexamethasone pharmacology   MeSH
• Financing, Organized MeSH
• Glucocorticoids pharmacology   MeSH
• Carcinoma, Hepatocellular enzymology   genetics   metabolism   MeSH
• Receptor Cross-Talk MeSH
• Humans MeSH
• RNA, Messenger metabolism   MeSH
• Cell Line, Tumor MeSH
• Liver Neoplasms enzymology   genetics   metabolism   MeSH
• Pilot Projects MeSH
• Polychlorinated Dibenzodioxins pharmacology   MeSH
• Receptors, Aryl Hydrocarbon agonists   genetics   metabolism   MeSH
• Receptors, Glucocorticoid agonists   genetics   metabolism   MeSH
• Gene Expression Regulation, Enzymologic drug effects   MeSH
• Signal Transduction drug effects   MeSH
• Transfection MeSH
• Check Tag
• Humans MeSH

The gut constitutes a prominent part of the immune system. Its commensal microflora plays an important role in defense and in tolerance to diet allergens. Disturbances in immune regulations may lead to food allergy. Among commensal bacteria, bifidobacteria are able to induce mechanisms of immune tolerance. Comprehension of their mutual cross-talk with the host is necessary for understanding their role in the diet and in food supplements.

• MeSH
• Anti-Infective Agents MeSH
• Bifidobacterium physiology   immunology   MeSH
• Cytokines MeSH
• Diet MeSH
• Financing, Organized MeSH
• Immune Tolerance MeSH
• Humans MeSH
• Food Hypersensitivity MeSH
• Dietary Supplements MeSH
• Probiotics MeSH
• Intestines immunology   microbiology   MeSH
• Inflammation MeSH
• Check Tag
• Humans MeSH

• MeSH
• Cell Line drug effects   MeSH
• Cytochrome P-450 CYP1A1 metabolism   drug effects   MeSH
• Dexamethasone pharmacology   MeSH
• Dioxins pharmacology   metabolism   MeSH
• Financing, Organized MeSH
• Glucocorticoids pharmacology   MeSH
• Receptor Cross-Talk drug effects   MeSH
• Humans MeSH
• Reverse Transcriptase Polymerase Chain Reaction methods   utilization   MeSH
• Receptors, Aryl Hydrocarbon drug effects   MeSH
• Repressor Proteins drug effects   MeSH
• Trophoblasts drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Abstracts MeSH

A seed's ability to properly germinate largely depends on its oxidative poise. The level of reactive oxygen species (ROS) in Arabidopsis (Arabidopsis thaliana) is controlled by a large gene network, which includes the gene coding for the hydrogen peroxide-scavenging enzyme, cytosolic ASCORBATE PEROXIDASE6 (APX6), yet its specific function has remained unknown. In this study, we show that seeds lacking APX6 accumulate higher levels of ROS, exhibit increased oxidative damage, and display reduced germination on soil under control conditions and that these effects are further exacerbated under osmotic, salt, or heat stress. In addition, ripening APX6-deficient seeds exposed to heat stress displayed reduced germination vigor. This, together with the increased abundance of APX6 during late stages of maturation, indicates that APX6 activity is critical for the maturation-drying phase. Metabolic profiling revealed an altered activity of the tricarboxylic acid cycle, changes in amino acid levels, and elevated metabolism of abscisic acid (ABA) and auxin in drying apx6 mutant seeds. Further germination assays showed an impaired response of the apx6 mutants to ABA and to indole-3-acetic acid. Relative suppression of abscisic acid insensitive3 (ABI3) and ABI5 expression, two of the major ABA signaling downstream components controlling dormancy, suggested that an alternative signaling route inhibiting germination was activated. Thus, our study uncovered a new role for APX6, in protecting mature desiccating and germinating seeds from excessive oxidative damage, and suggested that APX6 modulate the ROS signal cross talk with hormone signals to properly execute the germination program in Arabidopsis.

• MeSH
• Arabidopsis physiology   MeSH
• Ascorbate Peroxidases metabolism   MeSH
• Gene Expression MeSH
• Receptor Cross-Talk MeSH
• Germination * MeSH
• Abscisic Acid metabolism   MeSH
• Indoleacetic Acids metabolism   MeSH
• Mutation MeSH
• Oxidative Stress * MeSH
• Arabidopsis Proteins metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Water physiology   MeSH
• Hot Temperature MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Human gut microbiota exists in a complicated symbiotic relationship which postulates to impact health and disease conditions on the host. Interestingly, the gut microbiome shows different mechanisms to regulate host physiology and metabolism including cell-to-cell communications. But microbiota imbalance is characterized to change in the host normal functioning and lead to the development and progression of major human diseases. Therefore, the direct cross talk through the microbial metabolites or peptides suggests the evidence of host health and disease. Recent reports highlight the adaptation signals/small molecules promoting microbial colonization which allows modulating immunity of host and leads to pathogen colonization. Moreover, quorum sensing peptides are also evident in the involvement of host disease conditions. Here, we review the current understanding of the gut microbiota cross talk with mammalian cells through metabolites and peptides. These studies are providing insight into the prediction of signature molecules which significantly provide information for the understanding of the interaction for precision medicine applications.

• MeSH
• Bacteria growth & development   metabolism   MeSH
• Biomarkers metabolism   MeSH
• Dysbiosis microbiology   pathology   MeSH
• Bacterial Physiological Phenomena * MeSH
• Immunomodulation MeSH
• Humans MeSH
• Quorum Sensing MeSH
• Signal Transduction MeSH
• Gastrointestinal Microbiome physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• Publication type
• Meeting Abstract MeSH

The role of vitamin B6 as a key component in a number of biological events has been well established. Based on the relationship between chronic inflammation and carcinogenesis on the one hand, and the interaction between immune and cancer cells expressed by modulated cytokine production on the other hand, the aim of the present work was to examine the possibility that vitamin B6 affects cancer development by an interference in the cross-talk between human peripheral blood mononuclear cells (PBMC) and those from two colon carcinoma cell lines. Both non-stimulated PBMC and mononuclear cells induced for cytokine production by HT-29 and RKO cells from human colon carcinoma lines were incubated without and with 4, 20 and 100 μg/ml of pyridoxal hydrochloride (vitamin B6) and secretion of TNF-α, IL-1β, IL-6, IFN-γ, IL-10, and IL-1ra was examined. Vit B6 caused a dose-dependent decrease in production of all cytokines examined, except for that of IL-1ra. The results indicate that vitamin B6 exerts an immunomodulatory effect on human PBMC. The finding that production of inflammatory cytokines is more pronounced when PBMC are in contact with malignant cells and markedly inhibited by the vitamin suggests an additional way by which vitamin B6 may exert its carcinopreventive effect.

• MeSH
• Anti-Inflammatory Agents metabolism   MeSH
• Cytokines secretion   MeSH
• Adult MeSH
• Interferon-gamma secretion   MeSH
• Leukocytes, Mononuclear drug effects   immunology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Colonic Neoplasms immunology   pathology   MeSH
• Cell Survival drug effects   MeSH
• Vitamin B 6 pharmacology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH

Abnormal rates of growth together with metastatic potential and lack of susceptibility to cellular signals leading to apoptosis are widely investigated characteristics of tumors that develop via genetic or epigenetic mechanisms. Moreover, in the growing tumor, cells are exposed to insufficient nutrient supply, low oxygen availability (hypoxia) and/or reactive oxygen species. These physiological stresses force them to switch into more adaptable and aggressive phenotypes. This paper summarizes the role of two key mediators of cellular stress responses, namely p53 and HIF, which significantly affect cancer progression and compromise treatment outcomes. Furthermore, it describes cross-talk between these factors.

• MeSH
• Hypoxia-Inducible Factor 1 metabolism   MeSH
• Stress, Physiological MeSH
• Cell Hypoxia MeSH
• Carcinogenesis genetics   metabolism   MeSH
• Humans MeSH
• Tumor Suppressor Protein p53 metabolism   MeSH
• Neoplasms genetics   metabolism   MeSH
• DNA Damage * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The circadian clock is an endogenous timekeeper system that controls the daily rhythms of a variety of physiological processes. Accumulating evidence indicates that genetic changes or unhealthy lifestyle can lead to a disruption of circadian homeostasis, which is a risk factor for severe dysfunctions and pathologies including cancer. Cell cycle, proliferation, and cell death are closely intertwined with the circadian clock, and thus disruption of circadian rhythms appears to be linked to cancer development and progression. At the molecular level, the cell cycle machinery and the circadian clocks are controlled by similar mechanisms, including feedback loops of genes and protein products that display periodic activation and repression. Here, we review the circadian rhythmicity of genes associated with the cell cycle, proliferation, and apoptosis, and we highlight the potential connection between these processes, the circadian clock, and neoplastic transformations. Understanding these interconnections might have potential implications for the prevention and therapy of malignant diseases.

• MeSH
• Apoptosis genetics   physiology   MeSH
• Cell Cycle genetics   physiology   MeSH
• Circadian Clocks genetics   physiology   MeSH
• Circadian Rhythm physiology   MeSH
• Homeostasis MeSH
• Humans MeSH
• Cell Transformation, Neoplastic genetics   MeSH
• Neoplasms etiology   genetics   pathology   MeSH
• Cell Proliferation genetics   physiology   MeSH
• Risk Factors MeSH
• Life Style MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The ovarian follicle is the basic functional unit of the ovary, comprising theca cells and granulosa cells (GCs). Two different types of GCs, mural GCs and cumulus cells (CCs), serve different functions during folliculogenesis. Mural GCs produce oestrogen during the follicular phase and progesterone after ovulation, while CCs surround the oocyte tightly and form the cumulus oophurus and corona radiata inner cell layer. CCs are also engaged in bi-directional metabolite exchange with the oocyte, as they form gap-junctions, which are crucial for both the oocyte's proper maturation and GC proliferation. However, the function of both GCs and CCs is dependent on proper follicular angiogenesis. Aside from participating in complex molecular interplay with the oocyte, the ovarian follicular cells exhibit stem-like properties, characteristic of mesenchymal stem cells (MSCs). Both GCs and CCs remain under the influence of various miRNAs, and some of them may contribute to polycystic ovary syndrome (PCOS) or premature ovarian insufficiency (POI) occurrence. Considering increasing female fertility problems worldwide, it is of interest to develop new strategies enhancing assisted reproductive techniques. Therefore, it is important to carefully consider GCs as ovarian stem cells in terms of the cellular features and molecular pathways involved in their development and interactions as well as outline their possible application in translational medicine.

• MeSH
• Neovascularization, Physiologic * MeSH
• Stem Cells metabolism   MeSH
• Cumulus Cells metabolism   MeSH
• Humans MeSH
• Primary Ovarian Insufficiency metabolism   MeSH
• Polycystic Ovary Syndrome metabolism   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH