scholarly journals Dual Role of Metallic Trace Elements in Stress Biology—From Negative to Beneficial Impact on Plants

2019 ◽  
Vol 20 (13) ◽  
pp. 3117 ◽  
Author(s):  
Ewa Muszyńska ◽  
Mateusz Labudda
Keyword(s):  
Trace Elements ◽  
Molecular Mechanisms ◽  
Plant Protection ◽  
Model Systems ◽  
Elevated Concentration ◽  
Metallic Ions ◽  
Beneficial Effects ◽  
Metallic Trace Elements ◽  
Beneficial Impact ◽  
Evolutionary Consequences

Heavy metals are an interesting group of trace elements (TEs). Some of them are minutely required for normal plant growth and development, while others have unknown biological actions. They may cause injury when they are applied in an elevated concentration, regardless of the importance for the plant functioning. On the other hand, their application may help to alleviate various abiotic stresses. In this review, both the deleterious and beneficial effects of metallic trace elements from their uptake by roots and leaves, through toxicity, up to the regulation of physiological and molecular mechanisms that are associated with plant protection against stress conditions have been briefly discussed. We have highlighted the involvement of metallic ions in mitigating oxidative stress by the activation of various antioxidant enzymes and emphasized the phenomenon of low-dose stimulation that is caused by non-essential, potentially poisonous elements called hormesis, which is recently one of the most studied issues. Finally, we have described the evolutionary consequences of long-term exposure to metallic elements, resulting in the development of unique assemblages of vegetation, classified as metallophytes, which constitute excellent model systems for research on metal accumulation and tolerance. Taken together, the paper can provide a novel insight into the toxicity concept, since both dose- and genotype-dependent response to the presence of metallic trace elements has been comprehensively explained.

scholarly journals Pinpointing the PRDM9-PRDM7 Gene Duplication Event During Primate Divergence

2021 ◽  
Vol 12 ◽  
Author(s):  
Sacha Heerschop ◽  
Zahra Fagrouch ◽  
Ernst J. Verschoor ◽  
Hans Zischler
Keyword(s):  
Phylogenetic Tree ◽  
Molecular Mechanisms ◽  
Zinc Fingers ◽  
Hybrid Sterility ◽  
Duplication Event ◽  
Model Systems ◽  
Recent Common Ancestor ◽  
Most Recent Common Ancestor ◽  
Evolutionary Consequences ◽  
Exon 10

Studies on the function of PRDM9 in model systems and its evolution during vertebrate divergence shed light on the basic molecular mechanisms of hybrid sterility and its evolutionary consequences. However, information regarding PRDM9-homolog, PRDM7, whose origin is placed in the primate evolutionary tree, as well as information about the fast-evolving DNA-binding zinc finger array of strepsirrhine PRDM9 are scarce. Thus, we aimed to narrow down the date of the duplication event leading to the emergence of PRDM7 during primate evolution by comparing the phylogenetic tree reconstructions of representative primate samples of PRDM orthologs and paralogs. To confirm our PRDM7 paralogization pattern, database-deposited sequences were used to test the presence/absence patterns expected from the paralogization timing. In addition, we extended the existing phylogenetic tree of haplorrhine PRDM9 zinc fingers with their strepsirrhine counterparts. The inclusion of strepsirrhine zinc fingers completes the PRDM9 primate phylogeny. Moreover, the updated phylogeny of PRDM9 zinc fingers showed distinct clusters of strepsirrhine, tarsier, and anthropoid degenerated zinc fingers. Here, we show that PRDM7 emerged on the branch leading to the most recent common ancestor of catarrhines; therefore, its origin is more recent than previously expected. A more detailed character evolutionary study suggests that PRDM7 may have evolved differently in Cercopithecoidea as compared to Hominoidea: it lacks the first four exons in Old World monkeys orthologs and exon 10 in Papionini orthologs. Dating the origin of PRDM7 is essential for further studies investigating why Hominoidea representatives need another putative histone methyltransferase in the testis.

scholarly journals Medication-Related Osteonecrosis of the Jaw: New Insights into Molecular Mechanisms and Cellular Therapeutic Approaches

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Thomas Lombard ◽  
Virginie Neirinckx ◽  
Bernard Rogister ◽  
Yves Gilon ◽  
Sabine Wislet
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Osteonecrosis Of The Jaw ◽  
Pharmacological Treatments ◽  
Therapeutic Approaches ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Beneficial Impact ◽  
Antiangiogenic Drugs

In recent years, medication-related osteonecrosis of the jaw (MRONJ) became an arising disease due to the important antiresorptive drug prescriptions to treat oncologic and osteoporotic patients, as well as the use of new antiangiogenic drugs such as VEGF antagonist. So far, MRONJ physiopathogenesis still remains unclear. Aiming to better understand MRONJ physiopathology, the first objective of this review would be to highlight major molecular mechanisms that are known to be involved in bone formation and remodeling. Recent development in MRONJ pharmacological treatments showed good results; however, those treatments are not curative and could have major side effects. In parallel to pharmacological treatments, MSC grafts appeared to be beneficial in the treatment of MRONJ, in multiple aspects: (1) recruitment and stimulation of local or regional endogenous cells to differentiate into osteoblasts and thus bone formation, (2) beneficial impact on bone remodeling, and (3) immune-modulatory properties that decrease inflammation. In this context, the second objective of this manuscript would be to summarize the molecular regulatory events controlling osteogenic differentiation, bone remodeling, and osteoimmunology and potential beneficial effects of MSC related to those aspects, in order to apprehend MRONJ and to develop new therapeutic approaches.

Excitotoxicity as a Target Against Neurodegenerative Processes

2020 ◽  
Vol 26 (12) ◽  
pp. 1251-1262 ◽  
Author(s):  
Octavio Binvignat ◽  
Jordi Olloquequi
Keyword(s):  
Neurodegenerative Diseases ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Mitochondrial Dysfunctions ◽  
Beneficial Effects ◽  
Clinical Investigations ◽  
Turn Over ◽  
Excitotoxic Cell Death ◽  
Lateral Sclerosis

: The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as the injury and death of neurons due to excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. : Despite the anti-excitotoxic drug memantine has shown modest beneficial effects in some patients with dementia, to date, there is no effective treatment capable of halting or curing neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Huntington’s disease or amyotrophic lateral sclerosis. This has led to a growing body of research focusing on understanding the mechanisms associated with the excitotoxic insult and on uncovering potential therapeutic strategies targeting these mechanisms. : In the present review, we examine the molecular mechanisms related to excitotoxic cell death. Moreover, we provide a comprehensive and updated state of the art of preclinical and clinical investigations targeting excitotoxic- related mechanisms in order to provide an effective treatment against neurodegeneration.

Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Colorectal Carcinogenesis ◽  
Model Systems ◽  
Necrosis Factor Alpha ◽  
Multi Stage ◽  
Mechanistic Approach ◽  
Tnf Α ◽  
Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

scholarly journals The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 453
Author(s):  
Susana M. Chuva de Sousa Lopes ◽  
Marta S. Alexdottir ◽  
Gudrun Valdimarsdottir
Keyword(s):  
Stem Cell ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cell Model ◽  
Embryonic Stem ◽  
Model Systems ◽  
Special Focus ◽  
Placental Development

Emerging data suggest that a trophoblast stem cell (TSC) population exists in the early human placenta. However, in vitro stem cell culture models are still in development and it remains under debate how well they reflect primary trophoblast (TB) cells. The absence of robust protocols to generate TSCs from humans has resulted in limited knowledge of the molecular mechanisms that regulate human placental development and TB lineage specification when compared to other human embryonic stem cells (hESCs). As placentation in mouse and human differ considerably, it is only with the development of human-based disease models using TSCs that we will be able to understand the various diseases caused by abnormal placentation in humans, such as preeclampsia. In this review, we summarize the knowledge on normal human placental development, the placental disease preeclampsia, and current stem cell model systems used to mimic TB differentiation. A special focus is given to the transforming growth factor-beta (TGFβ) family as it has been shown that the TGFβ family has an important role in human placental development and disease.

scholarly journals Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cell ◽  
Physical Exercise ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Stem Cell Biology ◽  
Myocardial Repair ◽  
Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

scholarly journals Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Aerobic Exercise ◽  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Brain Regions ◽  
Synaptic Function ◽  
Molecular Changes ◽  
Beneficial Effects ◽  
The Impact

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.

scholarly journals Unveiling the Dynamics of KRAS4b on Lipid Model Membranes

2021 ◽  
Author(s):  
Cesar A. López ◽  
Animesh Agarwal ◽  
Que N. Van ◽  
Andrew G. Stephen ◽  
S. Gnanakaran
Keyword(s):  
Molecular Mechanisms ◽  
Hypervariable Region ◽  
Small Gtpase ◽  
Model Systems ◽  
Coarse Grained ◽  
Regulatory Function ◽  
Limited Information ◽  
Long Time ◽  
Cell Growth And Differentiation ◽  
State Models

AbstractSmall GTPase proteins are ubiquitous and responsible for regulating several processes related to cell growth and differentiation. Mutations that stabilize their active state can lead to uncontrolled cell proliferation and cancer. Although these proteins are well characterized at the cellular scale, the molecular mechanisms governing their functions are still poorly understood. In addition, there is limited information about the regulatory function of the cell membrane which supports their activity. Thus, we have studied the dynamics and conformations of the farnesylated KRAS4b in various membrane model systems, ranging from binary fluid mixtures to heterogeneous raft mimics. Our approach combines long time-scale coarse-grained (CG) simulations and Markov state models to dissect the membrane-supported dynamics of KRAS4b. Our simulations reveal that protein dynamics is mainly modulated by the presence of anionic lipids and to some extent by the nucleotide state (activation) of the protein. In addition, our results suggest that both the farnesyl and the polybasic hypervariable region (HVR) are responsible for its preferential partitioning within the liquid-disordered (Ld) domains in membranes, potentially enhancing the formation of membrane-driven signaling platforms. Graphic Abstract

scholarly journals Daily Lifestyle and Cutaneous Malignancies

2021 ◽  
Vol 22 (10) ◽  
pp. 5227
Author(s):  
Yu Sawada ◽  
Motonobu Nakamura
Keyword(s):  
Cell Carcinoma ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Human Life ◽  
Lifestyle Factors ◽  
Merkel Cell ◽  
Fundamental Part ◽  
Skin Cancers ◽  
Beneficial Impact ◽  
The Relationship

Daily lifestyle is a fundamental part of human life and its influence accumulates daily in the human body. We observe that a good daily lifestyle has a beneficial impact on our health; however, the actual effects of individual daily lifestyle factors on human skin diseases, especially skin cancers, have not been summarized. In this review, we focused on the influence of daily lifestyle on the development of skin cancer and described the detailed molecular mechanisms of the development or regulation of cutaneous malignancies. Several daily lifestyle factors, such as circadian rhythm disruption, smoking, alcohol, fatty acids, dietary fiber, obesity, and ultraviolet light, are known to be associated with the risk of cutaneous malignancies, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Although the influence of some daily lifestyles on the risk of skin cancers is controversial, this review provides us a better understanding of the relationship between daily lifestyle factors and skin cancers.

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