The nod-like receptor protein 3 (NLRP3) inflammasome has a critical role in inflammation damage in ischemic injury, and the activation of the inflammasome is closely related to the interaction with ...thioredoxin interacting protein (TXNIP), which dissociates from the thioredoxin1 (Trx1)/TXNIP complex under oxidative stress. However, the negative regulator of NLRP3 inflammasome activation has not been fully investigated. Nuclear factor erythroid 2-related factor 2 (Nrf2) takes on a critical part in the antioxidant stress system, that controls the driven genes of antioxidant response element (ARE). Activate Nrf2 could inhibit the activation of NLRP3 inflammasome in acute liver injury and severe lupus nephritis. We aimed to explore the protective effect of Nrf2 in inhibiting the NLPR3 inflammasome formulation through the Trx1/TXNIP complex in cerebral ischemia reperfusion (cerebral I/R) injury. Middle cerebral artery occlusion/reperfusion (MCAO/R) model was used to imitate ischemic insult. Nrf2 was activated by tert-butylhydroquinone (tBHQ) intraperitoneally (i.p.) injection (16.7mg/kg), Nrf2,Trx1 and NLRP3 siRNAs were infused into the left paracele (12μl per rat), protein and mRNA levels were assessed by Western blot, qRT-PCR. ELISA was used for IL-1β and IL-18 activity measurements. After upregulating Nrf2, the expression of TXNIP in cytoplasm, NLRP3 inflammasome, and downstream factors caspase-1, IL-18, and IL-1β were significantly reduced, and Nrf2 knockdown yielded the opposite results. Trx1 knockdown produced the same effect of Nrf2 inhibition and the protective effect of Nrf2 was mostly abolished. Our results suggested that Nrf2 acted as a protective regulator against NLRP3 inflammasome activation by regulating the Trx1/TXNIP complex, which could possibly represent an innovative insight into the treatment of ischemia and reperfusion injury.
Resveratrol has been reported to protect against cerebral ischemia/reperfusion (I/R) injury in rats, but the underlying mechanism is unclear. In the current study, we examined whether resveratrol ...ameliorates cerebral I/R injury by inhibiting NLRP3 inflammasome-derived inflammation and whether autophagy is involved in this process. In addition, we explored the role of Sirt1 in resveratrol-mediated protective effects.
To answer these questions, healthy male Sprague-Dawley rats were exposed to middle cerebral artery occlusion for 1h followed by 24h reperfusion.
We found that cerebral I/R increased levels of activated NLRP3 inflammasome, caspase-1, IL-1β, and IL-18 and enhanced autophagy activity (ratio of LC3B-II/LC3B-I and p62/SQSTM1). Treatment with resveratrol, a specific Sirt1 agonist, attenuated I/R-induced NLRP3 inflammasome-derived inflammation but upregulated autophagy. Furthermore, resveratrol treatment clearly reduced cerebral infarct volume, decreased brain water content, and improved neurological scores. In addition, inhibition of autophagy using 3-MA intracerebroventricular injection blocked the inhibitory effect of resveratrol on NLRP3 inflammasome activation. Finally, Sirt1 knockdown with siRNA significantly blocked resveratrol-induced enhancement of autophagy activity and suppression of NLRP3 inflammasome activation.
In conclusion, our results demonstrate that resveratrol protects against cerebral I/R injury by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy activity.
•Resveratrol treatment alleviates cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome activation•Resveratrol suppresses NLRP3 inflammasome activation by increasing autophagy activity•Sirt1 plays a vital role in resveratrol-mediated enhancement of autophagy activity•Sirt1-dependent autophagy activity is critical for resveratrol-mediated inhibition of NLRP3 inflammasome activation
Melatonin, an indoleamine widely found in animals and plants, is considered as a candidate phytohormone that affects responses to a variety of biotic and abiotic stresses. In plants, melatonin has a ...similar action to that of the auxin indole-3-acetic acid (IAA), and IAA and melatonin have the same biosynthetic precursor, tryptophan. Salt stress results in the rapid accumulation of melatonin in plants. Melatonin enhances plant resistance to salt stress in two ways: one is via direct pathways, such as the direct clearance of reactive oxygen species; the other is via an indirect pathway by enhancing antioxidant enzyme activity, photosynthetic efficiency, and metabolite content, and by regulating transcription factors associated with stress. In addition, melatonin can affect the performance of plants by affecting the expression of genes. Interestingly, other precursors and metabolite molecules associated with melatonin can also increase the tolerance of plants to salt stress. This paper explores the mechanisms by which melatonin alleviates salt stress by its actions on antioxidants, photosynthesis, ion regulation, and stress signaling.
A method was developed to establish a comprehensive anthropogenic VOC emission inventory in China, in which a four-level source categorization was proposed, and an emission factor determination ...system together with a reference database were developed. And this was applied to establish VOC emission inventories for the period 2008–2012. Results show China's anthropogenic VOC emissions increased from 22.45 Tg in 2008 to 29.85 Tg in 2012 at an annual average rate of 7.38%, with Shandong, Guangdong, Jiangsu, Zhejiang and Hebei provinces being the largest emitters. Industrial processes, transportation and solvent utilization were the key sources, accounting for 39.3%, 25.6%, and 14.9% of the total emissions in 2012, respectively. Passenger cars, biofuel combustion, coke production, field burning of biomass, and raw chemical manufacturing were the primary VOC sources nationwide. The key sources for each province were different because of the disparate industry and energy structure. China's VOC emissions displayed remarkable spatial variation, with emissions in the east and southeast regions being much larger than in the northwest, and the high emission areas mainly centered in the Bohai Economic Rim, the Yangtze River Delta, the Pearl River Delta and the Sichuan Basin. The size of high emission areas expanded over the period 2008–2012, with heavily polluted city clusters gradually emerging.
•A recognized method to establish the VOC emission inventory in China was proposed.•A four-level source classification and corresponding EFs database were developed.•China's VOC emissions had increased from 22.45 Tg in 2008 to 29.85 Tg in 2012.•Industrial process, transportation and solvent utilization are key VOC sources.•Highly polluted areas have expanded in 2008–2012, forming polluted city clusters.
Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, ...little is known about the mechanisms underlying the activation of this proto-oncogene in tumors.
Immunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation.
These data suggest that FECR1 circular RNA acts as an upstream regulator to control breast cancer tumor growth by coordinating the regulation of DNA methylating and demethylating enzymes. Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA.
Crosstalk between oocytes and surrounding somatic cells is crucial for mammalian oogenesis, but the structural mechanisms on oocytes to control female reproduction remain unknown. Here we combine ...endogenous-fluorescent tracing mouse models with a high-resolution live-cell imaging system to characterize oocyte-derived mushroom-like microvilli (Oo-Mvi), which mediate germ-somatic communication in mice. We perform 3D live-cell imaging to show that Oo-Mvi exhibit cellular characteristics that fit an exocrine function for signaling communication. We find that deletion of the microvilli-forming gene Radixin in oocytes leads to the loss of Oo-Mvi in ovaries, and causes a series of abnormalities in ovarian development, resulting in shortened reproductive lifespan in females. Mechanistically, we find that Oo-Mvi enrich oocyte-secreted factors and control their release, resulting in optimal selection of ovarian follicles. Taken together, our data show that the Oo-Mvi system controls the female reproductive lifespan by governing the fate of follicles.
Abstract
Using ArcGIS to analyze satellite derived PM
2.5
estimates, this paper obtains the average concentration and maximum concentration of fine particulate matter (PM
2.5
) in China's 31 ...provinces from 2002 to 2015. We adopt fixed effects model and spatial Durbin model to investigate the association between PM
2.5
and perinatal mortality rates. The results indicate that PM
2.5
has a significantly positive association with perinatal mortality rates. A 1% increase of log-transformed average concentration and maximum concentrations of PM
2.5
is associated with 1.76‰ and 2.31‰ increase of perinatal mortality rates, respectively. In spatial econometrics analysis, we find PM
2.5
has significant spatial autocorrelation characteristics. The concentrations of log-transformed average and maximum PM
2.5
increase 1% is associated with a 2.49% increase in a 2.49‰ and 2.19‰ increase of perinatal mortality rates, respectively. The potential mechanism is that air pollution has an impact on infant weight to impact perinatal mortality rates.
Multi-walled carbon nanotubes (MWNTs) were modified with poly(hexamethylene adipamide) (also known as Nylon 66) via a controlled polymer solution crystallization method. A “nanohybrid shish kebab” ...(NHSK) structure was found wherein the MWNT resembled the shish while Nylon 66 lamellar crystals formed the kebabs. These Nylon 66-functionalized MWNTs were used as precursors to prepare polymer/MWNT nanocomposites. Excellent dispersion was revealed by optical and electron microscopies. Nitric acid etching of the nanocomposites showed that MWNT formed a robust network in Nylon 66. Non-isothermal DSC results showed multiple melting peaks, which can be attributed to lamellar thickness changes upon heating. The crystallite sizes
L
100 and
L
010 of Nylon 66, determined by WAXD, decreased with increasing MWNT contents. Isothermal DSC results showed that crystallization kinetics increased first and then decreased with increasing MWNT contents in Nylon 66. This study showed that the effect of MWNTs on Nylon 66 crystallization is twofold: MWNTs provide heterogeneous nucleation sites for Nylon 66 crystallization while the tube network structure hinders large crystal growth.
Over the last decade, based on the extensive development of preclinical animal studies and clinical trials, the efficacy, and mechanisms of immunotherapy have been fully explored. Significant and ...lasting clinical responses with immunotherapy provide a new breakthrough treatment for a variety of refractory cancer histologies, which gradually change the treatment pattern of tumors. However, although immune checkpoint inhibitor drugs are promising for achieving longer-term efficacy, their benefits in the overall population are still very low, such as low frequency of response in some common tumor types such as breast and prostate, and heterogeneity in the degree of response among different tumor lesions in the same patient, making immunotherapy with many limitations and challenges. Most patients do not respond to immunotherapy or inevitably develop resistance to treatment after a period of treatment, manifesting with primary resistance or acquired resistance who initially respond to treatment. The mechanisms of tumor immune resistance are very complex and involve multiple aspects such as genes, metabolism, inflammation, and abnormal neovascularization. Currently, many mechanisms of immunotherapy resistance have been characterized, and more continue to be uncovered. These efforts can improve the quality of medical care for cancer diagnosis and treatment, which improve the quality of life of patients, and finally lead to accurate individualized treatment. This review discusses mechanisms of cancer immunotherapy resistance including tumor-intrinsic factors and tumor-extrinsic factors.
In this work, we comparatively analyzed the structure and antioxidant activities of different polysaccharide fractions from Arctium lappa L. A total of four water-soluble polysaccharide fractions ...(ALP-1, ALP-2, ALP-3 and ALP-4) were obtained from the roots of Arctium lappa L. They differed in monosaccharide composition, molecular weight and linkage mode. ALP-1 and ALP-2 mainly consisted of fructose, with average molecular weights of 2.676 × 103 and 2.503 × 104 g/mol, respectively. ALP-3 and ALP-4 were mainly composed of fructose, arabinose and galactose, with average molecular weights of 9.709 × 104 and 6.790 × 104 g/mol, respectively. Furthermore, Fourier transform infrared spectrometry, methylation analysis and nuclear magnetic resonance spectroscopy suggested that the main polysaccharide ALP-1 had a linear chain of (1 → 2)-linked β-D-Fructofuranosyl backbone (n ≈ 15) linked to a terminal (1 → 2)-linked α-d-Glucopyranosyl at the non-reducing end. All five polysaccharides displayed high antioxidant ability, especially ALP-4 in H2O2-induced HepG2 cell model and ALP-1 in metronidazole MET-induced zebrafish model. These findings provided comparative information on the structure and biological activity of different burdock polysaccharides and highlighted their potential as antioxidants in functional foods.
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•Four purified polysaccharide components were obtained from Arctium lappa L.•They differed in monosaccharide composition, molecular weight and linkage mode.•The main component had a (1 → 2)-linked β-D-Fructofuranosyl chain structure.•ALP-4 showed the most excellent antioxidant ability in H2O2-induced HepG2 cells.•ALP-1 had the best protective effect on metronidazole-damaged zebrafish embryos.
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