scholarly journals MOLECULAR MECHANISMS OF DEVELOPMENT OF CEREBRAL TOLERANCE TO ISCHEMIA (REVIEW. PART 2)

2012 ◽  
Vol 67 (7) ◽  
pp. 20-29
Author(s):  
E. V. Shlyakhto ◽  
E. R. Barantsevich ◽  
N. S. Shcherbak ◽  
M. M. Galagudza
Keyword(s):  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Regional Blood Flow ◽  
Ion Homeostasis ◽  
Antioxidant Systems ◽  
Ischemic And Reperfusion Injury ◽  
Mechanisms Of Development ◽  
Endogenous Antioxidant ◽  
The Impact

In the 2nd part the authors describe in details the main aspects of protective effect of preconditioning of the brain: inhibition of programmed cell death, weakening of phenomenon of excitotoxicity, activation of endogenous antioxidant systems, anti-inflammatory effects, modulation of glial cell function, changes in regional blood flow and vascular reactivity. In addition, data analysis on the impact of preconditioning on brain neurogenesis, the state of the blood-brain barrier, ion homeostasis and metabolism of neurons is presented. Review emphasizes the role of microRNAs in mechanisms of ischemic tolerance of brain. Profound understanding of molecular mechanisms of increased tolerance of brain to ischemic and reperfusion injury requires the implementation of this phenomenon in clinical practice. 

scholarly journals The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 201
Author(s):  
Rosa Vona ◽  
Lucia Pallotta ◽  
Martina Cappelletti ◽  
Carola Severi ◽  
Paola Matarrese
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Therapeutic Strategies ◽  
Gastrointestinal Disorders ◽  
Antioxidant Systems ◽  
New Techniques ◽  
Human Pathology ◽  
Substantial Progress ◽  
The Impact

Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies

scholarly journals Schistosome immunomodulators

2021 ◽  
Vol 17 (12) ◽  
pp. e1010064
Author(s):  
Sreemoyee Acharya ◽  
Akram A. Da’dara ◽  
Patrick J. Skelly
Keyword(s):  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Natural Infection ◽  
Host Cells ◽  
Anionic Polymer ◽  
Th2 Response ◽  
Anti Inflammatory ◽  
The Impact

Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to dampen host immune responses are described in this review. Adult worms express a collection of host-interactive tegumental ectoenzymes that can cleave host signaling molecules such as the “alarmin” ATP (cleaved by SmATPDase1), the platelet activator ADP (SmATPDase1, SmNPP5), and can convert AMP into the anti-inflammatory mediator adenosine (SmAP). SmAP can additionally cleave the lipid immunomodulator sphingosine-1-phosphate and the proinflammatory anionic polymer, polyP. In addition, the worms release a barrage of proteins (e.g., SmCB1, SjHSP70, cyclophilin A) that can impinge on immune cell function. Parasite eggs also release their own immunoregulatory proteins (e.g., IPSE/α1, omega1, SmCKBP) as do invasive cercariae (e.g., Sm16, Sj16). Some schistosome glycans (e.g., LNFPIII, LNnT) and lipids (e.g., Lyso-PS, LPC), produced by several life stages, likewise affect immune cell responses. The parasites not only produce eicosanoids (e.g., PGE2, PGD2—that can be anti-inflammatory) but can also induce host cells to release these metabolites. Finally, the worms release extracellular vesicles (EVs) containing microRNAs, and these too have been shown to skew host cell metabolism. Thus, schistosomes employ an array of biomolecules—protein, lipid, glycan, nucleic acid, and more, to bend host biochemistry to their liking. Many of the listed molecules have been individually shown capable of inducing aspects of the polarized Th2 response seen following infection (with the generation of regulatory T cells (Tregs), regulatory B cells (Bregs) and anti-inflammatory, alternatively activated (M2) macrophages). Precisely how host cells integrate the impact of these myriad parasite products following natural infection is not known. Several of the schistosome immunomodulators described here are in development as novel therapeutics against autoimmune, inflammatory, and other, nonparasitic, diseases.

scholarly journals On the Role of Paraoxonase-1, Chemokine (C-C motif) Ligand 2 and Metabolism in Oxidation, Inflammation and Disease. A 2021 Update

2021 ◽  
Author(s):  
Jordi Camps ◽  
Helena Castañé ◽  
Elisabet Rodríguez-Tomàs ◽  
Gerard Baiges-Gaya ◽  
Anna Hernández-Aguilera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Lipid Peroxides ◽  
Poor Quality ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Calorie Intake ◽  
Antioxidant Systems ◽  
Endogenous Antioxidant ◽  
Cellular Pathology

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

scholarly journals Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling

2015 ◽  
Vol 113 (3) ◽  
pp. E396-E405 ◽  
Author(s):  
Maira Diaz ◽  
Maria Jose Sanchez-Barrena ◽  
Juana Maria Gonzalez-Rubio ◽  
Lesia Rodriguez ◽  
Daniel Fernandez ◽  
...  
Keyword(s):  
Ion Transport ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Crop Improvement ◽  
Ion Homeostasis ◽  
Membrane Curvature ◽  
Dependent Manner ◽  
Membrane Function ◽  
Calcium Dependent ◽  
Small Proteins

Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca2+ are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca2+ signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca2+-dependent recruitment of the pyrabactin resistance 1/PYR1-like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca2+ sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca2+-dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress.

scholarly journals Strategy for Leukemia Treatment Targeting SHP-1,2 and SHIP

2021 ◽  
Vol 9 ◽  
Author(s):  
Fang Hao ◽  
Chen Wang ◽  
Christine Sholy ◽  
Min Cao ◽  
Xunlei Kang
Keyword(s):  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Fundamental Problem ◽  
Protein Tyrosine Phosphatases ◽  
Sh2 Domain ◽  
Human Leukemia ◽  
Molecular Signaling ◽  
Leukemia Treatment ◽  
The Impact

Protein tyrosine phosphatases (PTPs) are modulators of cellular functions such as differentiation, metabolism, migration, and survival. PTPs antagonize tyrosine kinases by removing phosphate moieties from molecular signaling residues, thus inhibiting signal transduction. Two PTPs, SHP-1 and SHP-2 (SH2 domain-containing phosphatases 1 and 2, respectively) and another inhibitory phosphatase, SH2 domain-containing inositol phosphatase (SHIP), are essential for cell function, which is reflected in the defective phenotype of mutant mice. Interestingly, SHP-1, SHP-2, and SHIP mutations are identified in many cases of human leukemia. However, the impact of these phosphatases and their mutations regarding the onset and progression of leukemia is controversial. The ambiguity of the role of these phosphatases imposes challenges on the development of targeting therapies for leukemia. This fundamental problem, confronted by the expanding investigational field of leukemia, will be addressed in this review, which will include a discussion of the molecular mechanisms of SHP-1, SHP-2, and SHIP in normal hematopoiesis and their role in leukemia. Clinical development of leukemic therapies achieved by targeting these phosphatases will be addressed as well.

scholarly journals Letter from the Editors

2020 ◽  
Vol 6 ◽  
Author(s):  
Tetyana L. Vasylyeva
Keyword(s):  
Molecular Mechanisms ◽  
Editorial Team ◽  
Care Providers ◽  
Double Blind ◽  
Blind Review ◽  
Modifiable Factors ◽  
Publishing Ethics ◽  
Mechanisms Of Development ◽  
The Impact

Since it was established in 2014, the International Journal of Integrative Pediatrics and Environmental Medicine (IJIPEM) has strongly adhered to publishing ethics, followed a double-blind review process, and published high-quality papers. Our outstanding linguistic service has assisted many grateful authors for whom English is a second language. Last year was a hard year for everyone, but particularly for the first-line medical care providers. We have given priority to SARS-CoV-2-related manuscripts and published them for free, thereby contributing to our universal knowledge of this new disease. One of the most interesting papers was "Pregnancy and COVID-19, a brief review", one of the first articles published on the topic. Another paper, "The new face of Medicine – care flow strategies developed during COVID" by Dr. Sharon Jacob, addressed how to adjust clinic schedules during this unexpected Global disaster. We also published rare and interesting cases related to the journal's scope, which is focused on the interactions between children and their physical and psychological environment. We want to remind you that the journal topics center on modifiable factors, such as environmental pollution, child-parent relationships, social circumstances, quality of life of the sick child, ill-child school performance, mental health, and sensitivity to environmental factors. Topics concerning integrating conventional pediatrics with complementary and alternative medicine for children and research about environmental impacts on cellular and molecular mechanisms of development are of great interest. We will continue giving priority to manuscripts related to the impact of SARS-CoV-2. We are hopeful that the new year will be very fruitful for our goal of increased scientific knowledge and distribution of these discoveries. We are looking forward to reading, reviewing, and publishing your work. We will also see that it is preserved and recorded with DOI links and advertised widely. Manuscripts funded by NIH or their partners will be indexed as PubMed selected citations. We hope you will enjoy working with our editorial team. If you are reading this letter, you may well already be familiar with IIPEM. If you are interested in working with us, please, register as an author on the web at https://ijipem.com/index.php/ijipem/login. We will put our talents to work to make your paper readable and visible.

scholarly journals N-myc Downstream Regulated Gene 1 (NDRG1) functions as a molecular switch for cellular adaptation to hypoxia

2021 ◽  
Author(s):  
Jong S. Park ◽  
Austin M. Gabel ◽  
Lois Kang ◽  
Bryanna Canales ◽  
Polina Kassir ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Function ◽  
Ion Homeostasis ◽  
Cell Types ◽  
Molecular Switch ◽  
Adaptation To Hypoxia ◽  
Dependent Manner ◽  
Low Oxygen ◽  
Metabolic Suppression ◽  
Lactate Levels

ABSTRACTLack of oxygen (hypoxia and anoxia) is detrimental to cell function and survival and underlies many disease conditions. Hence, metazoans have evolved mechanisms to adapt to low oxygen. One such mechanism, metabolic suppression, decreases the cellular demand for oxygen by downregulating ATP-demanding processes. However, the molecular mechanisms underlying this adaptation are poorly understood. Here, we report on the role of ndrg1a in hypoxia adaptation of the anoxia-tolerant zebrafish embryo. ndrg1a is expressed in the kidney and ionocytes, cell types that use large amounts of ATP to maintain ion homeostasis. ndrg1a mutants are viable and develop normally when raised under normal oxygen. However, their survival and kidney function is reduced relative to WT embryos following exposure to prolonged anoxia. We further demonstrate that Ndrg1a binds to the energy-demanding sodium-potassium ATPase (NKA) pump under anoxia and is required for its degradation. Consequently, ndrg1a mutants that fail to downregulate NKA, have reduced ATP levels compared to WT embryos. Lastly, we show that sodium azide treatment, which increased lactate levels, was sufficient to trigger NKA degradation in an Ndrg1a-dependent manner. These findings support a model whereby Ndrg1a functions as a molecular switch for long term adaptation to hypoxia via metabolic suppression.

scholarly journals On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 971
Author(s):  
Jordi Camps ◽  
Helena Castañé ◽  
Elisabet Rodríguez-Tomàs ◽  
Gerard Baiges-Gaya ◽  
Anna Hernández-Aguilera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Lipid Peroxides ◽  
Poor Quality ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Calorie Intake ◽  
Antioxidant Systems ◽  
Metabolic Alterations ◽  
Endogenous Antioxidant

Infectious and many non-infectious diseases share common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins, and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, both produce metabolic alterations that influence the pathogenesis of the disease. In this review, we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, inducing migration and infiltration of immune cells in target tissues and disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

The Impact of Ultraviolet Radiation on Barrier Function in Human Skin: Molecular Mechanisms and Topical Therapeutics

2019 ◽  
Vol 25 (40) ◽  
pp. 5503-5511 ◽  
Author(s):  
Abdulaziz Alhasaniah ◽  
Michael J. Sherratt ◽  
Catherine A. O'Neill
Keyword(s):  
Ultraviolet Radiation ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Transepidermal Water Loss ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Positive Effects ◽  
Terrestrial Mammals ◽  
The Impact

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

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