Cadmium (Cd) is a toxic heavy metal that accumulates in living systems. Exposure can occur occupationally or environmentally. Workers within the electroplating, battery production, and pigment ...industries are at the highest risk for exposure and have been reported to have increased levels of Cd in their blood and urine. Environmental exposure can be the result of anthropogenic activities or smoking. Cd has a long half-life and bio accumulates in plants, invertebrates, and vertebrates. The toxic effects following exposure include growth retardation and organ system toxicity, with kidney and liver toxicity most reported with in higher organisms. At the molecular level, Cd leads to the production of reactive oxygen species, DNA damage, and inhibition of DNA repair. This article gives a brief overview of the correlations between exposure to cadmium occupationally and environmentally and levels measured in blood and urine. It also examines the bioaccumulation of cadmium in aquatic invertebrates and vertebrates indicating that accumulation varies not only by location but also within and between various species.
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•Exposure to cadmium can occur occupationally of environmentally.•Cadmium exposure can be measured using blood and urine samples.•Cadmium bio accumulates in vertebrate and aquatic invertebrate organisms.•Free cadmium can accumulates aquatic organisms leading to biotransfer into vertebrates.•Cadmium exposure leads to ROS production and DNA damage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•ROS is both a trigger and an effector of NLRP3 inflammasome activation.•Ca2+ influx is upstream of NLRP3 inflammasome activation.•ADP-ribose (ADPR) activates TRPM2 under ROS in the NLRP3 ...pathway.•ADPR and Ca2+ co-activate TRPM2.•There exist drastic differences in TRPM2’s structure and function during evolution.
The NLRP3 inflammasome is an innate immune platform that senses various pathogens and sterile insults. NLRP3 stimulation leads to activation of caspase-1, the secretion of pro-inflammatory cytokines and an inflammatory cell death called pyroptosis. Effectors of the NLRP3 inflammasome efficiently drive an immune response, not only providing protection in physiological settings but also promoting pathology when over activated. Generation of reactive oxygen species (ROS) and intracellular calcium mobilization can activate the NLRP3 inflammasome. Recent studies suggest that TRPM2 is a calcium-permeable cation channel mediating ROS-dependent NLRP3 activation. Here, we review the role of TRPM2 in NLRP3 inflammasome activation and provide an update on new functional and structural discoveries. Understanding the molecular mechanism of TRPM2 dependent NLRP3 inflammasome activation will shed lights on this complex pathway and help the developing of therapeutic strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fibroblasts are diverse mesenchymal cells that participate in tissue homeostasis and disease by producing complex extracellular matrix and creating signaling niches through biophysical and ...biochemical cues. Transcriptionally and functionally heterogeneous across and within organs, fibroblasts encode regional positional information and maintain distinct cellular progeny. We summarize their development, lineages, functions, and contributions to fibrosis in four fibroblast-rich organs: skin, lung, skeletal muscle, and heart. We propose that fibroblasts are uniquely poised for tissue repair by easily reentering the cell cycle and exhibiting a reversible plasticity in phenotype and cell fate. These properties, when activated aberrantly, drive fibrotic disorders in humans.
A detailed mechanistic, molecular, and functional view of the commonalities and organ-specific features of fibroblasts in health and disease is just beginning to emerge.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With its content taken from only the very latest results, this is an extensive summary of the various polymeric materials used for biomedical applications. Following an introduction listing various ...functional polymers, including conductive, biocompatible and conjugated polymers, the book goes on to discuss different synthetic polymers that can be used, for example, as hydrogels, biochemical sensors, functional surfaces, and natural degradable materials. Throughout, the focus is on applications, with worked examples for training purposes as well as case studies included. The whole is rounded off with a look at future trends.
The association between mutations of key driver genes and colorectal cancer (CRC) metastasis has been investigated by many studies. However, the results of these studies have been contradictory. ...Here, we perform a comprehensive analysis to screen key driver genes from the TCGA database and validate the roles of these mutations in CRC metastasis. Using bioinformatics analysis, we identified six key driver genes, namely APC, KRAS, BRAF, PIK3CA, SMAD4 and p53. Through a systematic search, 120 articles published by November 30, 2017, were included, which all showed roles for these gene mutations in CRC metastasis. A meta-analysis showed that KRAS mutations (combined OR 1.18, 95% CI 1.05–1.33) and p53 mutations (combined OR 1.49, 95% CI 1.23–1.80) were associated with CRC metastasis, including lymphatic and distant metastases. Moreover, CRC patients with a KRAS mutation (combined OR 1.29, 95% CI 1.13–1.47), p53 mutation (combined OR 1.35, 95% CI 1.06–1.72) or SMAD4 mutation (combined OR 2.04, 95% CI 1.41–2.95) were at a higher risk of distant metastasis. Subgroup analysis stratified by ethnic populations indicated that the BRAF mutation was related to CRC metastasis (combined OR 1.42, 95% CI 1.18–1.71) and distant metastasis (combined OR 1.51, 95% CI 1.20–1.91) in an Asian population. No significant association was found between mutations of APC or PIK3CA and CRC metastasis. In conclusion, mutations of KRAS, p53, SMAD4 and BRAF play significant roles in CRC metastasis and may be both potential biomarkers of CRC metastasis as well as therapeutic targets.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after ...cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response.
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•The MKK4/5-MPK3/6 cascade negatively regulates freezing tolerance•The MEKK1-MKK2-MPK4 cascade positively regulates freezing tolerance•MPK3/6-mediated phosphorylation of ICE1 promotes ICE1 degradation•CRLK1 and CRLK2 suppress the cold activation of MPK3/6
ICE1 is a central regulator of the plant cold response, and its levels are tightly controlled. Zhao et al. show that cold-activated MPK3 and MPK6 phosphorylate ICE1 and promote its degradation, thus negatively regulating the cold response, whereas MPK4 positively regulates the cold response by constitutively suppressing MPK3 and MPK6 activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Much of brain science is concerned with understanding the neural circuits that underlie specific behaviors. While the mouse has become a favorite experimental subject, the behaviors of this species ...are still poorly explored. For example, the mouse retina, like that of other mammals, contains ∼20 different circuits that compute distinct features of the visual scene 1, 2. By comparison, only a handful of innate visual behaviors are known in this species—the pupil reflex 3, phototaxis 4, the optomotor response 5, and the cliff response 6—two of which are simple reflexes that require little visual processing. We explored the behavior of mice under a visual display that simulates an approaching object, which causes defensive reactions in some other species 7, 8. We show that mice respond to this stimulus either by initiating escape within a second or by freezing for an extended period. The probability of these defensive behaviors is strongly dependent on the parameters of the visual stimulus. Directed experiments identify candidate retinal circuits underlying the behavior and lead the way into detailed study of these neural pathways. This response is a new addition to the repertoire of innate defensive behaviors in the mouse that allows the detection and avoidance of aerial predators.
•Visual display of a looming dark disc triggers rapid escape or freezing in mice•These reactions are strongly dependent on the parameters of the visual stimulus•The selectivity of the behavior is consistent with specific retinal pathways
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chromium metal-organic framework (MIL-101(Cr)) has been widely studied for removing organic contaminants from aqueous solutions due to its excellent water stability and giant pore size, but its low ...adsorption capacity limits the application. In this study, a new adsorbent MIL-101 loaded with CuCo bimetallic nanoparticles (CuCo/MIL-101) was successfully fabricated and applied in removal of tetracycline (TC) from aqueous solutions. The adsorption capacity of CuCo/MIL-101 for TC increased by 140% compared with that of pure MIL-101, which may be attributed to the chemical bonding between Cu and Co BNPs in MIL-101 and TC molecules. The effects of pH, ionic strength, humic acid and contact time on the adsorption were also discussed in detail. The results showed that the removal efficiency of TC solution with high concentration (100 mg L−1) by CuCo/MIL-101 was still as high as 82.9%. The data of adsorption kinetics and isotherms could be well fitted by Elovich model and Freundlich model, respectively. According to the fitting parameters, the maximum adsorption capacity of CuCo/MIL-101 reached up to 225.179 mg g−1. Additionally, the adsorption process of TC onto CuCo/MIL-101 was spontaneous and endothermic. Electrostatic interactions could play an important role in the adsorption process. The enhanced adsorption capacity, excellent reusability and water stability demonstrated the potential of CuCo/MIL-101 composite as a novel adsorbent for the removal of TC from aqueous solutions.
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•MIL-101 doped with Cu and Co bimetallic nanoparticles was utilized as an adsorbent to remove tetracycline for the first time.•The synergistic effect between Cu and Co made the adsorption capacity of CuCo/MIL-101 significantly enhanced.•Electrostatic interaction played an important role in the adsorption process.•The good reusability and stability of CuCo/MIL-101 proved its potential to remove tetracycline from actual wastewater.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Long noncoding RNAs modulate various transcriptional programs and miRNA expression.•LncRNA-HOTAIR and its genetic variants play crucial role in human carcinogenesis.•Knockdown of HOTAIR suppresses ...tumor invasion and metastasis.•Aberrant HOTAIR expression contributes to chemoresistance in various cancers.•HOTAIR exhibits the potential of reliable biomarker in clinical diagnosis of cancers.
Long non-coding RNAs (lncRNAs) are an important novel class of non-coding RNAs having lengths of 200 nucleotides and low expression. The HOX Transcript Antisense Intergenic RNA (HOTAIR) is one of the most extensively studied lncRNAs found dysregulated in human cancer. Although a growing body of evidence suggests a role fo HOTAIR in pathogenesis, disease progression, drug resistance and reduced survival, its mechanism of action remains largely unclear. Recent studies have identified that HOTAIR facilitates protein-protein interaction thereby affecting diverse pathways in cancer such as epigenetic reprogramming, protein stability and signal transduction. HOTAIR has been shown to promote tumor progression by regulating microRNA expression and function. Moreover, several HOTAIR gene variants have recently been identified and found to increase cancer susceptibility. Here we review recent data on the critical role of HOTAIR in human malignancy and its potential mechanism of action. A more comprehensive understanding of this unique lncRNA is critical to elucidating the pro-oncogenic function of HOTAIR its potential application in diagnosis, prognosis and treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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