scholarly journals Omic markers identification for predicting risks of negative effects in children with elevated copper and nickel contents in blood

2021 ◽  
pp. 48-56
Author(s):  
N.V. Zaitseva ◽  
◽  
M.A. Zemlyanova ◽  
Yu.V. Koldibekova ◽  
N.I. Bulatova ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Reference Group ◽  
Ambient Air ◽  
Relative Volume ◽  
Cellular Damage ◽  
Proteomic Profiling ◽  
Negative Effects ◽  
Anchor Protein ◽  
Apolipoprotein A ◽  
Research Goal

Proteomic profiling is a promising procedure for examining and substantiating molecular mechanisms of body reactions occurrence and development as a response to adverse impacts; it allows detecting and examining these reactions at early stages in their development prior to cellular damage and damage to organs. Studies aimed at increasing efficiency of adverse effects prediction are especially vital for solving tasks related to early detection and prevention of consequences associated with exposure to chemical environmental factors, first of all, ambient air. Our research goal was to identify omic-markers for predicting risks of negative effects in children with elevated copper and nickel contents in blood. We performed proteomic blood plasma examination in children and modeled cause-and-effect relations. Children with copper and nickel contents in their blood being 3.5 times higher than physiological standard had approximately 20 protein stains that were authentically different from those detected in children from the reference group. We detected correlations between an increase in relative volume of three protein stains including apolipoprotein A-I, anchor protein of A-kinase 9, vitronectin, and a decrease in relative volume of one protein strain including transthyretin and elevated copper and nickel contents in blood (R2=0.30–0.44; р=0.0001–0.008). All the above-mentioned proteins have predictive significance when it comes down to negative effects related to neuroregulation disorders and endothelial dysfunction. It was proven that there was a risk of predicted negative effects such as greater frequency of nervous and cardiovascular system diseases in case copper and nickel contents in blood were elevated (R2=0.35–0.96; р=0.0001–0.013). The established list of potential target molecules (apolipoprotein A-I, vitronectin, anchor protein of A-kinase 9, and transthyretin) and genes that coded their expression (APOA1, VTN,AKAP9,TTR) was substantiated as omic-markers indicating a possibility that negative effects might occur in the cardiovascular and nervous system.

scholarly journals Omic markers identification for predicting risks of negative effects in children with elevated copper and nickel contents in blood

2021 ◽  
pp. 48-56
Author(s):  
N.V. Zaitseva ◽  
◽  
M.A. Zemlyanova ◽  
Yu.V. Koldibekova ◽  
N.I. Bulatova ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Reference Group ◽  
Ambient Air ◽  
Relative Volume ◽  
Cellular Damage ◽  
Proteomic Profiling ◽  
Negative Effects ◽  
Anchor Protein ◽  
Apolipoprotein A ◽  
Research Goal

Proteomic profiling is a promising procedure for examining and substantiating molecular mechanisms of body reactions occurrence and development as a response to adverse impacts; it allows detecting and examining these reactions at early stages in their development prior to cellular damage and damage to organs. Studies aimed at increasing efficiency of adverse effects prediction are especially vital for solving tasks related to early detection and prevention of consequences associated with exposure to chemical environmental factors, first of all, ambient air. Our research goal was to identify omic-markers for predicting risks of negative effects in children with elevated copper and nickel contents in blood. We performed proteomic blood plasma examination in children and modeled cause-and-effect relations. Children with copper and nickel contents in their blood being 3.5 times higher than physiological standard had approximately 20 protein stains that were authentically different from those detected in children from the reference group. We detected correlations between an increase in relative volume of three protein stains including apolipoprotein A-I, anchor protein of A-kinase 9, vitronectin, and a decrease in relative volume of one protein strain including transthyretin and elevated copper and nickel contents in blood (R2=0.30–0.44; р=0.0001–0.008). All the above-mentioned proteins have predictive significance when it comes down to negative effects related to neuroregulation disorders and endothelial dysfunction. It was proven that there was a risk of predicted negative effects such as greater frequency of nervous and cardiovascular system diseases in case copper and nickel contents in blood were elevated (R2=0.35–0.96; р=0.0001–0.013). The established list of potential target molecules (apolipoprotein A-I, vitronectin, anchor protein of A-kinase 9, and transthyretin) and genes that coded their expression (APOA1, VTN,AKAP9,TTR) was substantiated as omic-markers indicating a possibility that negative effects might occur in the cardiovascular and nervous system.

Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

2020 ◽  
Vol 16 (1) ◽  
pp. 85-89
Author(s):  
Mahesh M. Gouda ◽  
Ashwini Prabhu ◽  
Varsha Reddy S.V. ◽  
Rafa Jahan ◽  
Yashodhar P. Bhandary
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Plasminogen Activator Inhibitor ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Alveolar Epithelial Cells ◽  
Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

scholarly journals PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubrey N. Michi ◽  
Bryan G. Yipp ◽  
Antoine Dufour ◽  
Fernando Lopes ◽  
David Proud
Keyword(s):  
Host Defense ◽  
Barrier Function ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cellular Damage ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Epithelial Damage

AbstractHuman rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

scholarly journals Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 308
Author(s):  
Marion Buffard ◽  
Aurélien Naldi ◽  
Gilles Freiss ◽  
Marcel Deckert ◽  
Ovidiu Radulescu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Burkitt Lymphoma ◽  
Molecular Mechanisms ◽  
Signal Propagation ◽  
Tumor Formation ◽  
Tissue Type ◽  
Signaling Networks ◽  
Proteomic Profiling

Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression.

scholarly journals Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1676
Author(s):  
Giulia Rossi ◽  
Martina Placidi ◽  
Chiara Castellini ◽  
Francesco Rea ◽  
Settimio D'Andrea ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Cellular Damage ◽  
X Rays ◽  
Adolescent Cancer ◽  
Radiation Induced ◽  
Vitro Model ◽  
Underlying Mechanisms

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

scholarly journals Proteomic Profiling Reveals the Molecular Changes of Insomnia Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Guanying Wang ◽  
Xiaojuan Ren ◽  
Xingping Zhang ◽  
Qingquan Wang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Sleep Onset ◽  
Public Health Problem ◽  
Sleep Time ◽  
Control Group ◽  
Proteomic Profiling ◽  
Ppi Network ◽  
Metabolic Systems ◽  
Hub Proteins

Background. Insomnia is an economic burden and public health problem. This study is aimed at exploring potential biological pathways and protein networks for insomnia characterized by wakefulness after sleep. Method. Proteomics analysis was performed in the insomnia group with wakefulness and the control group. The differentially expressed proteins (DEPs) were enriched; then, hub proteins were identified by protein-protein interaction (PPI) network and verified by parallel reaction monitoring (PRM). Results. Compared with the control group, the sleep time and efficiency of insomnia patients were decreased, and awakening time and numbers after sleep onset were significantly increased ( P < 0.001 ). The results of proteomic sequencing found 68 DEPs in serum under 1.2-fold changed standard. These DEPs were significantly enriched in humoral immune response, complement and coagulation cascades, and cholesterol metabolism. Through the PPI network, we identified 10 proteins with the highest connectivity as hub proteins. Among them, the differential expression of 9 proteins was verified by PRM. Conclusion. We identified the hub proteins and molecular mechanisms of insomnia patients characterized by wakefulness after sleep. It provided potential molecular targets for the clinical diagnosis and treatment of these patients and indicated that the immune and metabolic systems may be closely related to insomnia characterized by wakefulness after sleep.

scholarly journals Risk of sensitization to ecopollutants in teenagers with inherited chemical burden

2021 ◽  
pp. 123-131
Author(s):  
L.B. Masnavieva ◽  
◽  
N.V. Efimova ◽  
I.V. Kudaeva ◽  
◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Hazard Index ◽  
Allergic Diseases ◽  
Ambient Air ◽  
Inhibition Test ◽  
Immune Disorders ◽  
Migration Inhibition ◽  
Air Contamination ◽  
Relative Risks ◽  
Research Goal

At present allergic diseases are detected in 30% people and their frequency is only growing. A significant role in allergic pathology occurrence belongs to ambient air contamination and chemicals being introduced not only into children’s bodies, but their parents’ ones as well since pollutants can act as allergens and sensitizing agents. Our research goal was to examine influence exerted by parents’ pre-gestation exposure to chemicals on sensitization among teenagers living in an area where ambient air was contaminated. We examined overall immunoglobulin E contents and leukocytes migration inhibition test with formaldehyde and sodium nitrite in 115 teenagers whose parents worked under adverse working conditions at chemical and petrochemical enterprises and in 244 schoolchildren whose parents didn’t have any occupational contacts with chemicals. Each group was divided into sub-groups depending on inhalation chemical burden on schoolchildren’s bodies caused by ambient air contamination and contaminated air indoors (with hazard index (HI) for immune disorders being lower than 2 and HI≥2). The research allowed establishing that teenagers whose parents had worked at chemical and petrochemical enterprises during a pre-gestation period had elevated IgE contents more frequently as well as changes in leukocytes migration inhibition test with formaldehyde; it indicated there was sensitization to this chemical. Parents’ occupational contacts with chemicals led to an increase in relative risks of elevated igE contents and 2.5 times higher sensitization among schoolchildren with HI<2. Risk that sensitization to formaldehyde might occur was equal to 2.3 among senior schoolchildren with HI≥2 whose parents worked at chemical enterprises.

Exploring Air Pollution and COVID-19 Linkages in South Asia

2021 ◽  
Author(s):  
Muthukumara Mani ◽  
Takahiro Yamada
Keyword(s):  
Air Pollution ◽  
South Asia ◽  
Measurement Errors ◽  
Ambient Air ◽  
The Body ◽  
Ambient Air Pollution ◽  
Cellular Damage ◽  
Pollution Level ◽  
Form Analysis ◽  
Risk Of Death

South Asia is at the epicenter of the global air pollution problems and still evolving in COVID-19 cases and fatalities. There is growing evidence of increased rates of COVID-19 in areas with high levels of air pollution. Air pollution is found to cause cellular damage and inflammation throughout the body and has been linked to higher rates of diseases, including cancer, heart disease, stroke, diabetes, asthma, and other comorbidities. All these conditions also potentially increase the risk of death in COVID-19 patients. The causal link between the exposure to air pollution and COVID-19 is still under investigation around the world, underpinned by rigorous scientific research and peer-review processes. However, in terms of the approach after a careful review of the literature, the instrumental variable (IV) approach is a prospective candidate to establish causality in a reduced-form analysis to overcome endogeneity and measurement errors of air pollution level. An analysis, therefore, using sufficiently anonymized individual and household level information on COVID-19, household air pollution, and other individual and household socioeconomic endowments in the same primary sampling unit (PSU) of the individual and household survey would be necessary to establish the causality. The PSU data are usually available from demographic health surveys (DHS) with randomly displaced location information to maintain anonymity. Also, for the instrument of the exposure to ambient air pollution, the use of thermal inversions is suggested conditional on weather-related variables—for example, temperature, precipitation, wind velocity and direction, and humidity.

Potential Health Benefits Of A Pomegranate Extract, Rich In Phenolic Compounds, In Intestinal Inflammation

2021 ◽  
Vol 17 ◽  
Author(s):  
Marco Raffaele ◽  
Khaled Greish ◽  
Luca Vanella ◽  
Giuseppe Carota ◽  
Fatemah Bahman ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Inflammatory Marker ◽  
Experimental Models ◽  
Cellular Damage ◽  
Experimental Conditions ◽  
Potential Health

Background: Pomegranate is a fruit rich in bioactive compounds such as punicalagins, gallic acid, and ellagic acid derivatives. It has been widely used since ancient times in traditional medicine for a wide variety of diseases. It has been reported that bioactive compounds, such as polyphenols, are able to induce the expression of cytoprotective enzymes, including HO-1. The contribution of HO-1 activity to the prevention of intestinal inflammation has been shown in different models of Inflammatory bowel diseases (IBD). Objective: Aim of the present research was to investigate the molecular mechanisms involved in the beneficial effects of a pomegranate extract (PE), rich in bioactive compounds in intestinal inflammation. Methods: Caco-2 cells exposed to LPS and DSS induced colitis were chosen as convenient experimental models of intestinal inflammation. Results: Results obtained in our experimental conditions, showed that PE in vitro was able to induce HO-1 and to reduce cellular damage and oxidative stress through increase of GSH levels. Moreover, PE was able to decrease the pro-inflammatory marker IL-8 levels and to activate TIGAR pathway. The results obtained in vivo, in agreement with the data obtained in vitro, highlighted the ability of PE to reduce intestinal inflammation, preserve the colon length and histological features and reduce IL-6 levels compared to the DSS treated group. Conclusion: PE, rich in bioactive compounds, could contribute, as supportive therapy, to enhance the effects of the conventional therapeutic strategies to the management of IBD.

scholarly journals Cerebral sterile inflammation in neurodegenerative diseases

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Kento Otani ◽  
Takashi Shichita
Keyword(s):  
Immune Responses ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Agents ◽  
Sterile Inflammation ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Abnormal Accumulation ◽  
The Brain ◽  
Lateral Sclerosis

AbstractTherapeutic strategies for regulating neuroinflammation are expected in the development of novel therapeutic agents to prevent the progression of central nervous system (CNS) pathologies. An understanding of the detailed molecular and cellular mechanisms of neuroinflammation in each CNS disease is necessary for the development of therapeutics. Since the brain is a sterile organ, neuroinflammation in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) is triggered by cerebral cellular damage or the abnormal accumulation of inflammatogenic molecules in CNS tissue through the activation of innate and acquired immunity. Inflammation and CNS pathologies worsen each other through various cellular and molecular mechanisms, such as oxidative stress or the accumulation of inflammatogenic molecules induced in the damaged CNS tissue. In this review, we summarize the recent evidence regarding sterile immune responses in neurodegenerative diseases.

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