scholarly journals The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1852
Author(s):  
Gemma Aragonès ◽  
Sheldon Rowan ◽  
Sarah G. Francisco ◽  
Elizabeth A. Whitcomb ◽  
Wenxin Yang ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Nutritional Intervention ◽  
Cellular Aging ◽  
Dependent Manner ◽  
Glyoxalase System ◽  
Protective Mechanisms ◽  
Protein Levels ◽  
Current State ◽  
Age Related ◽  
Nutritional Compounds

The glyoxalase system is critical for the detoxification of advanced glycation end-products (AGEs). AGEs are toxic compounds resulting from the non-enzymatic modification of biomolecules by sugars or their metabolites through a process called glycation. AGEs have adverse effects on many tissues, playing a pathogenic role in the progression of molecular and cellular aging. Due to the age-related decline in different anti-AGE mechanisms, including detoxifying mechanisms and proteolytic capacities, glycated biomolecules are accumulated during normal aging in our body in a tissue-dependent manner. Viewed in this way, anti-AGE detoxifying systems are proposed as therapeutic targets to fight pathological dysfunction associated with AGE accumulation and cytotoxicity. Here, we summarize the current state of knowledge related to the protective mechanisms against glycative stress, with a special emphasis on the glyoxalase system as the primary mechanism for detoxifying the reactive intermediates of glycation. This review focuses on glyoxalase 1 (GLO1), the first enzyme of the glyoxalase system, and the rate-limiting enzyme of this catalytic process. Although GLO1 is ubiquitously expressed, protein levels and activities are regulated in a tissue-dependent manner. We provide a comparative analysis of GLO1 protein in different tissues. Our findings indicate a role for the glyoxalase system in homeostasis in the eye retina, a highly oxygenated tissue with rapid protein turnover. We also describe modulation of the glyoxalase system as a therapeutic target to delay the development of age-related diseases and summarize the literature that describes the current knowledge about nutritional compounds with properties to modulate the glyoxalase system.

scholarly journals Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

scholarly journals Cellular Aging Characteristics and Their Association with Age-Related Disorders

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 94 ◽  
Author(s):  
Magdalena Rudzińska ◽  
Alessandro Parodi ◽  
Anastasia V. Balakireva ◽  
Olga E. Chepikova ◽  
Franco M. Venanzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cellular Senescence ◽  
Current Knowledge ◽  
Cell Metabolism ◽  
Critical Role ◽  
Cellular Aging ◽  
Molecular Signaling ◽  
Age Related ◽  
Organelle Communication ◽  
Metabolic Dysfunctions

Different molecular signaling pathways, biological processes, and intercellular communication mechanisms control longevity and are affected during cellular senescence. Recent data have suggested that organelle communication, as well as genomic and metabolic dysfunctions, contribute to this phenomenon. Oxidative stress plays a critical role by inducing structural modifications to biological molecules while affecting their function and catabolism and eventually contributing to the onset of age-related dysfunctions. In this scenario, proteins are not adequately degraded and accumulate in the cell cytoplasm as toxic aggregates, increasing cell senescence progression. In particular, carbonylation, defined as a chemical reaction that covalently and irreversibly modifies proteins with carbonyl groups, is considered to be a significant indicator of protein oxidative stress and aging. Here, we emphasize the role and dysregulation of the molecular pathways controlling cell metabolism and proteostasis, the complexity of the mechanisms that occur during aging, and their association with various age-related disorders. The last segment of the review details current knowledge on protein carbonylation as a biomarker of cellular senescence in the development of diagnostics and therapeutics for age-related dysfunctions.

scholarly journals Age-Related Neuroprotection by Dietary Restriction Requires OXR1-Mediated Retromer Function

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 562-562
Author(s):  
Sudipta Bar ◽  
George Brownridge ◽  
Jennifer Beck ◽  
Rachel Brem ◽  
Hugo Bellen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dietary Restriction ◽  
Disease Diagnosis ◽  
Lifespan Extension ◽  
Dependent Manner ◽  
Physical Decline ◽  
Protein Levels ◽  
Age Related ◽  
Multiple Species

Abstract Dietary restriction (DR) is the most robust method to delay aging and the onset of neurogenerative disorders across multiple species, though the mechanisms behind this phenomenon remain unknown. To elucidate how DR mediates lifespan extension, we analyzed natural genetic variants that associate with increased longevity under DR conditions in the Drosophila Genetic Reference Panel. We found that neuronal expression of the fly homolog of human Oxidation Resistance 1 (OXR1) is necessary for DR-mediated lifespan extension. Neuronal knockdown of OXR1 also accelerated visual decline but not physical decline, arguing for a specific role of OXR1 in neuronal signaling. Further, we find that overexpression of the TLDc domain from human OXR1 is sufficient for lifespan extension in a diet-dependent manner. Studies from the Accelerating Medicines Partnership - Alzheimer's Disease network show that patients with reduced OXR1 protein levels are more prone to Alzheimer's disease diagnosis, and we find that overexpression of human OXR1 is protective in animal and cell Alzheimer's models. In seeking the mechanism by which OXR1 protects against age-related neuronal decline, we discovered that it provides a necessary function in regulating the neuronal retromer complex, which is essential for the recycling of transmembrane receptors and for maintenance of autophagy. We further discovered that OXR1 deficiency can be rescued by genetic or pharmacological enhancement of retromer function, and that this enhancement extends lifespan and healthspan. Understanding how OXR1 operates could help uncover novel mechanisms to slow neurodegeneration including Alzheimer's disease.

scholarly journals Treadmill Training Increases SIRT-1 and PGC-1αProtein Levels and AMPK Phosphorylation in Quadriceps of Middle-Aged Rats in an Intensity-Dependent Manner

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Nara R. C. Oliveira ◽  
Scherolin O. Marques ◽  
Thais F. Luciano ◽  
José R. Pauli ◽  
Leandro P. Moura ◽  
...  
Keyword(s):  
Training Session ◽  
Treadmill Training ◽  
Dependent Manner ◽  
Aged Rats ◽  
Middle Aged ◽  
Protein Levels ◽  
Ampk Phosphorylation ◽  
Age Related ◽  
Male Wistar Rats ◽  
Inflammatory Proteins

The present study investigated the effects of running at 0.8 or 1.2 km/h on inflammatory proteins (i.e., protein levels of TNF-α, IL-1β, and NF-κB) and metabolic proteins (i.e., protein levels of SIRT-1 and PGC-1α, and AMPK phosphorylation) in quadriceps of rats. Male Wistar rats at 3 (young) and 18 months (middle-aged rats) of age were divided into nonexercised (NE) and exercised at 0.8 or 1.2 km/h. The rats were trained on treadmill, 50 min per day, 5 days per week, during 8 weeks. Forty-eight hours after the last training session, muscles were removed, homogenized, and analyzed using biochemical and western blot techniques. Our results showed that: (a) running at 0.8 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with NE rats; (b) these responses were lower for the inflammatory proteins and higher for the metabolic proteins in young rats compared with middle-aged rats; (c) running at 1.2 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with 0.8 km/h; (d) these responses were similar between young and middle-aged rats when trained at 1.2 km. In summary, the age-related increases in inflammatory proteins, and the age-related declines in metabolic proteins can be reversed and largely improved by treadmill training.

Alzheimer’s Disease and Retinal Degeneration: A Glimpse at Essential Trace Metals in Ocular Fluids and Tissues

2020 ◽  
Vol 16 (12) ◽  
pp. 1073-1083 ◽  
Author(s):  
Alessandra Micera ◽  
Luca Bruno ◽  
Andrea Cacciamani ◽  
Mauro Rongioletti ◽  
Rosanna Squitti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Trace Metals ◽  
Late Onset ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Retinal Disease ◽  
Cellular Aging ◽  
Research Strategies ◽  
Aged People

Background: Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more common in the developing world and characterize principally aged people. Agerelated Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation and amyloid formations. Method: In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The possibility to find out new research strategies represent a step forward to disclose potential treatment for both of them. Essential trace metals play critical roles in both physiological and pathological condition of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial pathogenesis. Conclusion: Hence, this review addresses current knowledge about some up-to-date investigated essential trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways shared with AD, which might open to potential early detection.

The Natural Flavonoid Naringenin Inhibits the Cell Growth of WilmsTumorinChildren by Suppressing TLR4/NF-κB Signaling

2020 ◽  
Vol 20 ◽  
Author(s):  
Hongtao Li ◽  
Peng Chen ◽  
Lei Chen ◽  
Xinning Wang
Keyword(s):  
Cell Growth ◽  
Western Blot ◽  
Wilms Tumor ◽  
Critical Role ◽  
Time Dependent ◽  
Luciferase Assay ◽  
Dependent Manner ◽  
Tlr4 Expression ◽  
Protein Levels

Background: Nuclear factor kappa B (NF-κB) is usually activated in Wilms tumor (WT) cells and plays a critical role in WT development. Objective: The study purpose was to screen a NF-κB inhibitor from natural product library and explore its effects on WT development. Methods: Luciferase assay was employed to assess the effects of natural chemical son NF-κB activity. CCK-8 assay was conducted to assess cell growth in response to naringenin. WT xenograft model was established to analyze the effect of naringenin in vivo. Quantitative real-time PCR and Western blot were performed to examine the mRNA and protein levels of relative genes, respectively. Results: Naringenin displayed significant inhibitory effect on NF-κB activation in SK-NEP-1 cells. In SK-NEP-1 and G-401 cells, naringenin inhibited p65 phosphorylation. Moreover, naringenin suppressed TNF-α-induced p65 phosphorylation in WT cells. Naringenin inhibited TLR4 expression at both mRNA and protein levels in WT cells. CCK-8 staining showed that naringenin inhibited cell growth of the two above WT cells in dose-and time-dependent manner, whereas Toll-like receptor 4 (TLR4) over expression partially reversed the above phenomena. Besides, naringenin suppressed WT tumor growth in dose-and time-dependent manner in vivo. Western blot found that naringenin inhibited TLR4 expression and p65 phosphorylation in WT xenograft tumors. Conclusion: Naringenin inhibits WT development viasuppressing TLR4/NF-κB signaling

Platelet-Rich and Platelet-Poor Plasma Might Play Supportive Roles in Cancer Cell Culture: A Replacement for Fetal Bovine Serum?

2021 ◽  
Vol 21 ◽  
Author(s):  
Mehdi Talebi ◽  
Mousa Vatanmakanian ◽  
Ali Mirzaei ◽  
Yaghoub Barfar ◽  
Maryam Hemmatzadeh ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Growth ◽  
Cancer Cell ◽  
Human Cancer ◽  
High Price ◽  
Dependent Manner ◽  
Platelet Poor Plasma ◽  
Protein Levels ◽  
Healthy Donors ◽  
Regulatory Functions

Background: Platelet-rich (PRP) and Platelet-poor plasma (PPP) are widely used in research and clinical platforms mainly due to their capacities to enhance cell growth. Although short half-life (5 days) and the high price of platelet products pose challenges regarding their usage, they maintain the growth regulatory functions for weeks. Thus, we aimed to assess the supplementary values of these products in human CCRF-CEM cancer cells. Mechanistically, we also checked if the PRP/PPP treatment enhances YKL-40 expression as a known protein regulating cell growth. Methods: The PRP/PPP was prepared from healthy donors using manual stepwise centrifugation and phase separation. The viability of the cells treated with gradient PRP/PPP concentrations (2, 5, 10, and 15%) was measured by the MTT assay. The YKL-40 mRNA and protein levels were assessed using qRT-PCR and western blotting. The data were compared to FBS-treated cells. Result: Our findings revealed that the cells treated by PRP/PPP not only were morphologically comparable to those treated by FBS but also, they showed greater viability at the concentrations of 10 and 15%. Moreover, it was shown that PRP/PPP induce cell culture support, at least in part, via inducing YKL-40 expression at both mRNA and protein levels in a time- and dose-dependent manner. Conclusion: Collectively, by showing cell culture support comparable to FBS, the PRP/PPP might be used as good candidates to supplement the cancer cell culture and overcome concerns regarding the use of FBS as a non-human source in human cancer research.

The Oxford Handbook of the Auditory Brainstem

2018 ◽  
Keyword(s):  
Current Knowledge ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Midbrain ◽  
Current State ◽  
Neuronal Mechanisms ◽  
Maladaptive Plasticity ◽  
And Function ◽  
Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

scholarly journals A review of current knowledge of myeloproliferative disorders in the horse

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Katy Satué ◽  
Juan Carlos Gardon ◽  
Ana Muñoz
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Chronic Granulocytic Leukemia ◽  
Current State ◽  
Multiple Cell ◽  
Health Organization

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

scholarly journals Nursing Interventions to Prevent Delirium in Critically Ill Patients in the Intensive Care Unit during the COVID19 Pandemic—Narrative Overview

Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 578
Author(s):  
Dorota Ozga ◽  
Sabina Krupa ◽  
Paweł Witt ◽  
Wioletta Mędrzycka-Dąbrowska
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Critically Ill Patients ◽  
Current Knowledge ◽  
Personalised Medicine ◽  
Nursing Interventions ◽  
Evidence Based ◽  
Current State ◽  
Scientific Disciplines ◽  
Reliable Methods

It has become a standard measure in recent years to utilise evidence-based practice, which is associated with a greater need to implement and use advanced, reliable methods of summarising the achievements of various scientific disciplines, including such highly specialised approaches as personalised medicine. The aim of this paper was to discuss the current state of knowledge related to improvements in “nursing” involving management of delirium in intensive care units during the SARS-CoV-2 pandemic. This narrative review summarises the current knowledge concerning the challenges associated with assessment of delirium in patients with COVID-19 by ICU nurses, and the role and tasks in the personalised approach to patients with COVID-19.

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