scholarly journals Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

2021 ◽  
Vol 22 (11) ◽  
pp. 5722
Author(s):  
Alessandro de Sire ◽  
Nicola Marotta ◽  
Cinzia Marinaro ◽  
Claudio Curci ◽  
Marco Invernizzi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Synergistic Effects ◽  
Molecular Pathways ◽  
Epigenetic Changes ◽  
Pathological Features ◽  
Oxidative Signaling ◽  
Cartilage Extracellular Matrix ◽  
Wide Range ◽  
Comprehensive Picture

Osteoarthritis (OA) is a painful and disabling disease that affects millions of patients. Its etiology is largely unknown, but it is most likely multifactorial. OA pathogenesis involves the catabolism of the cartilage extracellular matrix and is supported by inflammatory and oxidative signaling pathways and marked epigenetic changes. To delay OA progression, a wide range of exercise programs and naturally derived compounds have been suggested. This literature review aims to analyze the main signaling pathways and the evidence about the synergistic effects of these two interventions to counter OA. The converging nutrigenomic and physiogenomic intervention could slow down and reduce the complex pathological features of OA. This review provides a comprehensive picture of a possible signaling approach for targeting OA molecular pathways, initiation, and progression.

scholarly journals STAT3, a Hub Protein of Cellular Signaling Pathways, Is Triggered by β-Hexaclorocyclohexane

2018 ◽  
Vol 19 (7) ◽  
pp. 2108 ◽  
Author(s):  
Elisabetta Rubini ◽  
Fabio Altieri ◽  
Silvia Chichiarelli ◽  
Flavia Giamogante ◽  
Stefania Carissimi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cellular Signaling ◽  
Environmental Pollutants ◽  
Altered Expression ◽  
Exposed Population ◽  
Wide Range ◽  
Hepg2 Cell Lines

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 μM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect.

scholarly journals Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1232
Author(s):  
Stefania D’Adamo ◽  
Silvia Cetrullo ◽  
Veronica Panichi ◽  
Erminia Mariani ◽  
Flavio Flamigni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Antioxidant Activities ◽  
Synergistic Effects ◽  
National Health System ◽  
Bioactive Molecules ◽  
Joint Disease ◽  
In Vivo Studies ◽  
Wide Range

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.

scholarly journals LSD1, a double-edged sword, confers dynamic chromatin regulation but commonly promotes aberrant cell growth

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2016 ◽  
Author(s):  
Meghan M Kozub ◽  
Ryan M Carr ◽  
Gwen L Lomberk ◽  
Martin E Fernandez-Zapico
Keyword(s):  
Gene Expression ◽  
Chromatin Remodeling ◽  
Cellular Differentiation ◽  
Critical Role ◽  
Histone Demethylase ◽  
Epigenetic Changes ◽  
Lysine Specific Demethylase ◽  
Wide Range ◽  
Histone Modifying Enzymes

Histone-modifying enzymes play a critical role in chromatin remodeling and are essential for influencing several genome processes such as gene expression and DNA repair, replication, and recombination. The discovery of lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, dramatically revolutionized research in the field of epigenetics. LSD1 plays a pivotal role in a wide range of biological operations, including development, cellular differentiation, embryonic pluripotency, and disease (for example, cancer). This mini-review focuses on the role of LSD1 in chromatin regulatory complexes, its involvement in epigenetic changes throughout development, and its importance in physiological and pathological processes.

Reviewing the role of precipitation and soil moisture in driving the terrestrial carbon cycle variability in Europe: recent advances and known unknowns

2020 ◽  
Author(s):  
Gabriele Messori ◽  
Guiomar Ruiz-Pérez ◽  
Stefano Manzoni ◽  
Giulia Vico
Keyword(s):  
Soil Moisture ◽  
Carbon Cycle ◽  
Climate Indices ◽  
Terrestrial Carbon ◽  
Terrestrial Carbon Cycle ◽  
Wide Range ◽  
Holistic Understanding ◽  
Comprehensive Picture ◽  
Known Unknowns

<p>The terrestrial biosphere is a key component of the global carbon cycle and is heavily influenced by climate. This interaction spans a wide range of temporal (from sub-daily to paleoclimatic) and spatial (from local to continental and global) scales and a multitude of bio-physical processes. In part due to this complexity, a comprehensive picture of the physical links and correlations between climate drivers and carbon cycle metrics at different scales remains elusive, framing the scope of this contribution. Here, we specifically explore how precipitation, soil moisture and aggregated climate variability indices relate to the variability of the European terrestrial carbon cycle at sub-daily to interannual scales (i.e. excluding long-term trends). We first discuss broad areas of agreement and disagreement in the literature. For example, while most carbon cycle proxies tend to correlate positively with precipitation, responses to soil moisture and climate indices are more variable. In fact, soil moisture often correlates positively with productivity in water-limited environments, and negatively in light limited ones, or can exhibit nonlinear relations with the carbon cycle proxies. We then conclude by outlining some existing knowledge gaps and by proposing avenues for improving our holistic understanding of the role of climate drivers in modulating the terrestrial carbon cycle.</p>

Stress is a critical player in CYP3A, CYP2C, and CYP2D regulation: role of adrenergic receptor signaling pathways

2012 ◽  
Vol 303 (1) ◽  
pp. E40-E54 ◽  
Author(s):  
Evangelos P. Daskalopoulos ◽  
Foteini Malliou ◽  
Georgia Rentesi ◽  
Marios Marselos ◽  
Matti A. Lang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Adrenergic Receptor ◽  
Drug Efficacy ◽  
Stress System ◽  
Wide Range ◽  
Repeated Restraint Stress ◽  
Pharmacological Manipulations

Stress is a critical player in the regulation of the major cytochrome P-450s ( CYPs) that metabolize the majority of the prescribed drugs. Early in life, maternal deprivation (MD) stress and repeated restraint stress (RS) modified CYP expression in a stress-specific manner. In particular, the expression of CYP3A1 and CYP2C11 was increased in the liver of MD rats, whereas RS had no significant effect. In contrast, hepatic CYP2D1/2 activity was increased by RS, whereas MD did not affect it. The primary effectors of the stress system, glucocorticoids and epinephrine, highly induced CYP3A1/2. Epinephrine also induced the expression of CYP2C11 and CYP2D1/2. Further investigation indicated that AR-agonists may modify CYP regulation. In vitro experiments using primary hepatocyte cultures treated with the AR-agonists phenylephrine, dexmedetomidine, and isoprenaline indicated an AR-induced upregulating effect on the above-mentioned CYPs mediated by the cAMP/protein kinase A and c-Jun NH2-terminal kinase signaling pathways. Interestingly though, in vivo pharmacological manipulations of ARs using the same AR-agonists led to a suppressed hepatic CYP expression profile, indicating that the effect of the complex network of central and peripheral AR-linked pathways overrides that of the hepatic ARs. The AR-mediated alterations in CYP3A1/2, CYP2C11, and CYP2D1/2 expressions are potentially connected with those observed in the activation of signal transducer and activator of transcription 5b. In conclusion, stress and AR-agonists may modify the expression of the major CYP genes involved in the metabolism of drugs used in a wide range of diseases, thus affecting drug efficacy and toxicity.

scholarly journals Epigenetic Signaling of Cancer Stem Cells During Inflammation

2021 ◽  
Vol 9 ◽  
Author(s):  
Zaoqu Liu ◽  
Yuqing Ren ◽  
Lingfang Meng ◽  
Lifeng Li ◽  
Richard Beatson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Malignant Tumors ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Tumor Treatment ◽  
Smad Pathway ◽  
The Relationship

Malignant tumors pose a great challenge to human health, which has led to many studies increasingly elucidating the tumorigenic process. Cancer Stem Cells (CSCs) have profound impacts on tumorigenesis and development of drug resistance. Recently, there has been increased interest in the relationship between inflammation and CSCs but the mechanism underlying this relationship has not been fully elucidated. Inflammatory cytokines produced during chronic inflammation activate signaling pathways that regulate the generation of CSCs through epigenetic mechanisms. In this review, we focus on the effects of inflammation on cancer stem cells, particularly the role of signaling pathways such as NF-κB pathway, STAT3 pathway and Smad pathway involved in regulating epigenetic changes. We hope to provide a novel perspective for improving strategies for tumor treatment.

Potential role of melatonin in prevention and treatment of leukaemia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ming Guan Ng ◽  
Khuen Yen Ng ◽  
Rhun Yian Koh ◽  
Soi Moi Chye
Keyword(s):  
Shift Work ◽  
Potential Role ◽  
Synergistic Effects ◽  
Melatonin Receptors ◽  
Anticancer Compounds ◽  
Future Studies ◽  
Wide Range ◽  
Incidence Risk ◽  
The Relationship

Abstract Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually increase leukaemia incidence risk. Melatonin, a pineal hormone, has shown promising oncostatic properties on a wide range of cancers, including leukaemia. We first reviewed the relationship between shift work and the incidence rate of leukaemia and then discussed the role of melatonin receptors (MT1 and MT2) and their functions in leukaemia. Moreover, the connection between inflammation and leukaemia, and melatonin-induced anti-leukaemia mechanisms including anti-proliferation, apoptosis induction and immunomodulation are comprehensively discussed. Apart from that, the synergistic effects of melatonin with other anticancer compounds are also included. In short, this review article has compiled the evidence of anti-leukaemia properties displayed by melatonin and discuss its potential to act as adjunct for anti-leukaemia treatment. This review may serve as a reference for future studies or experimental research to explore the possibility of melatonin serving as a novel therapeutic agent for leukaemia.

scholarly journals Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency

2018 ◽  
Vol 63 (2) ◽  
pp. e01744-18 ◽  
Author(s):  
Benni Vargas ◽  
Nicholas S. Giacobbi ◽  
Anwesha Sanyal ◽  
Narasimhan J. Venkatachari ◽  
Feng Han ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor ◽  
Kinase C ◽  
Wide Range ◽  
Latent Hiv ◽  
Hiv 1

ABSTRACT Signaling pathways play a key role in HIV-1 latency. In this study, we used the 24ST1NLESG cell line of HIV-1 latency to screen a library of structurally diverse, medicinally active, cell permeable kinase inhibitors, which target a wide range of signaling pathways, to identify inhibitors of HIV-1 latency reversal. The screen was carried out in the absence or presence of three mechanistically distinct latency-reversing agents (LRAs), namely, prostratin, panobinostat, and JQ-1. We identified inhibitors that only blocked the activity of a specific LRA, as well as inhibitors that blocked the activity of all LRAs. For example, we identified 12 inhibitors targeted toward protein kinase C or downstream kinases that blocked the activity of prostratin. We also identified 12 kinase inhibitors that blocked the reversal of HIV-1 latency irrespective of the LRA used in the screen. Of these, danusertib, an Aurora kinase inhibitor, and PF-3758309, a PAK4 inhibitor, were the most potent. The 50% inhibitory concentrations in the 24ST1NLESG cells ranged from 40 to 147 nM for danusertib (selectivity indices, >150) and from 0.1 to 1 nM for PF-3758309 (selectivity indices, >3,300). Both danusertib and PF-3758309 inhibited latency reversal in CD4+ T cells isolated from HIV-1-infected donors. Collectively, our study describes a chemical approach that can be applied to elucidate the role of signaling pathways involved in LRA activity or the maintenance of HIV-1 latency and also identifies inhibitors of latent HIV-1 reactivation that could be used with antiretroviral therapy to reduce residual viremia.

scholarly journals The Functions of the Demethylase JMJD3 in Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 968
Author(s):  
Anna Sanchez ◽  
Fatma Zohra Houfaf Khoufaf ◽  
Mouhamed Idrissou ◽  
Frédérique Penault-Llorca ◽  
Yves-Jean Bignon ◽  
...  
Keyword(s):  
Epigenetic Mark ◽  
Cancer Type ◽  
Epigenetic Changes ◽  
Scientific Review ◽  
H3k27 Methylation ◽  
Histone 3 ◽  
Wide Range ◽  
Development Data ◽  
Sports Activities

Cancer is a major cause of death worldwide. Epigenetic changes in response to external (diet, sports activities, etc.) and internal events are increasingly implicated in tumor initiation and progression. In this review, we focused on post-translational changes in histones and, more particularly, the tri methylation of lysine from histone 3 (H3K27me3) mark, a repressive epigenetic mark often under- or overexpressed in a wide range of cancers. Two actors regulate H3K27 methylation: Jumonji Domain-Containing Protein 3 demethylase (JMJD3) and Enhancer of zeste homolog 2 (EZH2) methyltransferase. A number of studies have highlighted the deregulation of these actors, which is why this scientific review will focus on the role of JMJD3 and, consequently, H3K27me3 in cancer development. Data on JMJD3’s involvement in cancer are classified by cancer type: nervous system, prostate, blood, colorectal, breast, lung, liver, ovarian, and gastric cancers.

scholarly journals Crosstalk between Fat Mass and Obesity-related (FTO) and multiple WNT signaling pathways

2021 ◽  
Author(s):  
Hyunjoon Kim ◽  
Soohyun Jang ◽  
Young-suk Lee
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Fat Mass ◽  
Wide Spectrum ◽  
Rna Regulation ◽  
Public Data ◽  
Wide Range ◽  
Cell Type Specific ◽  
Canonical Wnt

Fat Mass and Obesity-related (FTO) gene is associated with a diverse set of human diseases. Yet, the functional landscape of FTO remains largely unknown, most likely owing to its wide range of mechanistic roles and cell-type-specific targets. Here, we discover the intricate role of FTO in multiple WNT signaling pathways. Re-analyses of public data identified the bifurcation of canonical and noncanonical WNT pathways as the major role of FTO. In FTO-depleted cells, we find that the canonical WNT/β-Catenin signaling is inhibited in a non-cell autonomous manner via the upregulation of DKK1. Simultaneously, this upregulation of DKK1 promotes cell migration via activating the noncanonical WNT/PCP pathway. Unexpectedly, we also find that the canonical WNT/STOP signaling induces the accumulation of cytoplasmic FTO proteins. This subsequently leads to the stabilization of mRNAs via RNA demethylation, revealing a previously uncharacterized mode of WNT action in RNA regulation. Altogether, this study places the functional context of FTO at the branching point of multiple WNT signaling pathways which may explain the wide spectrum of FTO functions.

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