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Particulate matter 2.5 (PM2.5) induces lung injury by increasing the generation of reactive oxygen species (ROS) and inflammation. ROS aggravates NLRP3 inflammasome activation, which activates caspase-1, IL-1β, and IL-18 and induces pyroptosis; these factors propagate inflammation. In contrast, treatment with exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases RAC1 activity and eventually decreases dinucleotide phosphate oxidase (NOX) and ROS generation. To establish modalities that would mitigate PM2.5-induced lung injury, we evaluated whether 8-OHdG decreased PM2.5-induced ROS generation and NLRP3 inflammasome activation in BEAS-2B cells. CCK-8 and lactate dehydrogenase assays were used to determine the treatment concentration. Fluorescence intensity, Western blotting, enzyme-linked immunosorbent assay, and immunoblotting assays were also performed. Treatment with 80 μg/mL PM2.5 increased ROS generation, RAC1 activity, NOX1 expression, NLRP3 inflammasome (NLRP3, ASC, and caspase-1) activity, and IL-1β and IL-18 levels in cells; treatment with 10 μg/mL 8-OHdG significantly attenuated these effects. Furthermore, similar results, such as reduced expression of NOX1, NLRP3, ASC, and caspase-1, were observed in PM2.5-treated BEAS-2B cells when treated with an RAC1 inhibitor. These results show that 8-OHdG mitigates ROS generation and NLRP3 inflammation by inhibiting RAC1 activity and NOX1 expression in respiratory cells exposed to PM2.5. [ABSTRACT FROM AUTHOR]

Abstract Background Cadmium(Cd), a heavy metal, which has a potent harmful effects, is a highly stress-inducible material that is robustly expressed following disruption of homeostasis in the endoplasmic reticulum (ER) (so-called ER stress). The mechanism Cd induced cell death of neuroblastoma cells complex, involving cellular signaling pathways as yet incompletely defined but, in part, involving the generation of reactive oxygen species (ROS). Several studies have correlated GADD153 expression with cell death, but a mechanistic link between GADD153 and apoptosis has never been demonstrated. Results SH-SY5Y cells were treated Cd led to increase in intracellular ROS levels. ROS generation is not consistent with intracellular [Ca2+]. The exposure of neuroblastoma cells to Cd led to increase in intracellular GADD153 and Bak levels in a doses and time dependent manner. The induction of these genes by Cd was attenuated by NAC. Cd-induced apoptosis is decreased in GADD153 knockdown cells compared with normal cells. The effect of GADD153 on the binding of C/EBP to the Bak promoters were analyzed ChIP assay. Basal constitutive GADD153 recruitment to the –3,398/–3,380 region of the Bak promoter is observed in SH-SY5Y cells. Conclusions The exposure of SH-SY5Y cells to Cd led to increase in intracellular ROS levels in a doses and time dependent manner. The generation of ROS result in the induction of GADD153 is causative of cadmium-induced apoptosis. GADD153 regulates Bak expression by its binding to promoter region (between −3,398 and −3,380). Therefore, we conclude that GADD153 sensitizes cells to ROS through mechanisms that involve up-regulation of BAK and enhanced oxidant injury.

Abstract Background Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD). Peripheral blood markers have been used to assess biochemical changes associated with AD and mild cognitive impairment (MCI) and involved in their pathophysiology. Methods Plasma samples and clinical data were obtained from participants in the Ansan Geriatric Study (AGE study). Plasma concentrations of four candidate biomarkers were measured in the normal control (NC), MCI, and AD group: interleukin-8 (IL-8), IL-10, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α). Body mass index (BMI), MMSE (Mini Mental State Examination), CDR(Clinical Dementia Rating) score and homocystein level were recorded with social and demographic information. Results Total of 59 subjects were randomly selected for this analysis [NC (n = 21), MCI(n = 20) and AD(n = 18)]. In demographic data, educational year was correlated with the diagnosis states (p < 0.0001). No significant differences in cardiovascular disease, BMI and use of NSAIDs were found in MCI or AD group compared with NC group, respectively. The involvement of inflammatory illness or conditions in subjects, WBC count, fibrinogen and homocystein of the three groups, but no significant differences were found in each groups. The plasma IL-8 level was lower in MCI and AD patients compared with the normal control group (respectively, p < 0.0001). The MCI and AD patients had similar MCP-1, IL-10, and TNF-α level. Conclusions Our study suggests the existence of an independent and negative relationship between plasma IL-8 levels and functional status in MCI and AD patients.

Biobanks are infrastructures for large-scale biology innovation. Governance of biobanks can be usefully informed by studies of publication trends, for example, on the types of biosamples employed in scientific publications. We examined trends in each of the serum, plasma, peripheral blood mononuclear cell (PBMC), buffy coat, tissue, and gut microbiome biosample-related scientific publications over the past 40 years, using data between 1977 and 2016 from the Scopus database. We found that the number of tissue-related publications was the highest in each year of our analysis than other biosamples, but was generally less than the sum of serum- and plasma-related publications. Importantly, the microbiome publications increased greatly starting in the 2010s, and currently overtook the number of publications on PBMC and buffy coat. Among serum-, plasma-, and tissue-related publications, the number of protein- and RNA-related publications was generally higher than cell-free DNA-, DNA-, and metabolite-related publications for the past 40 years. Mass spectrometry- and next-generation sequencing-related publications have increased dramatically since the 2000s and 2010s, respectively. Microbiome- and metabolite-related biosamples can help diversify future biosample collections, while tissue collections appear to maintain their importance in scientific publications. We also report here our observations on the countries that use biosample research (e.g., China, United Kingdom, United States, and others). These publication trends by the type of biosamples illuminate roadmaps by which biobanks might establish and diversify their biosample collections in the future. In addition, we note that biobanks need to secure biosamples appropriate for integrated analysis of multi-omics research data.

Research data and outcomes do vary across populations and persons, but this is not always due to experimental or true biological variation. Preanalytical components of experiments, be they biospecimen acquisition, preparation, storage, or transportation to the laboratory, may all contribute to apparent variability in research data, outcomes, and interpretation. The present review article and biobanking innovation analysis offer new insights with a summary of such preanalytical variables, for example, the type of blood collection tube, centrifugation conditions, long-term sample storage temperature, and duration, on output of omics analyses of blood-derived biospecimens: whole blood, serum, plasma, buffy coat, and peripheral blood mononuclear cells. Furthermore, we draw parallels from the field of precision medicine in this study, with a view to the future of "precision biobanking" wherein such preanalytical variations are carefully taken into consideration so as to minimize their influence on outcomes of omics data, analyses, and sensemaking, particularly in clinical omics applications. We underscore the need for using broadly framed, critical, independent, social and political science, and humanities research so as to understand the multiple possible future trajectories of, and the motivations and values embedded in, precision biobanking that is increasingly relevant in the current age of Big Data.

The different isoforms of the uncoupling protein-3 (UCP3) are expressed in skeletal muscle and are up-regulated by splicing factors. Here, we report that UCP3 alternative splicing (alternative polyadenylation) is regulated by cooperation between the splicing factor ASF/SF2 and the transcription factor PPAR-gamma. We found that ASF/SF2 activates formation of long-form UCP3 (UCP3(L)) by inhibiting a cleavage and polyadenylation signal (AATAAA) located in its final intron that prematurely terminates message elongation. PPAR-gamma activates this process by directly interacting with ASF/SF2, providing the first example of a direct link between a transcription factor and alternative splicing. Activation of ASF/SF2 promotes formation of UCP3(L), whereas loss of ASF/SF2 decreases production of both UCP3(L) and short-form UCP3 (UCP3(S)). We suggest that the relative abundance of ASF/SF2 and PPAR-gamma determines the ratio of UCP3 isoforms.