ABSTRACT
BACKGROUND: Excessive deposition of uric acid (UA) is one of the risk factors for kidney damage. Qinling liquid (QL) has a certain therapeutic effect on uric acid nephropathy (UAN), but its regulation mechanism is still unclear. METHODS: UAN rat models and UA induced rat renal tubular epithelial cells (NRK-52E) were constructed to evaluate the functional roles of QL. We firstly evaluated the kidney function and the degree of kidney damage in rats after QL treatment. Then, effects of QL on autophagy and NLRP3 inflammasome activation were assessed. Moreover, the regulation of QL in AMPK and Stat3 phosphorylation levels and the relationship among autophagy, AMPK/Stat3 pathway and NLRP3 inflammasomes were determined. RESULTS: QL could alleviate the inflammatory damage in UAN rats and promote the activation of autophagy. In addition, QL suppressed UA-induced activation of NLRP3 inflammasomes in rat renal tubular epithelial cells, which was partially reversed by autophagy inhibitor. Further, AMPK/Stat3 axis-mediated autophagy participated in the regulation of UA-induced NLRP3 inflammasome activation in NRK-52E cells. Finally, we confirmed that inhibiting AMPK/Stat3 pathway partly deteriorated the ameliorating effect of QL on renal immune inflammatory injury in UAN rats. CONCLUSION: Through in vivo and in vitro experiments, we found that QL promotes autophagy by activating the AMPK/Stat3 pathway, thereby improving renal immune inflammatory injury in UAN.
Subject(s)
Inflammasomes , Kidney Diseases , Rats , Animals , Inflammasomes/metabolism , AMP-Activated Protein Kinases/metabolism , Uric Acid/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Kidney Diseases/metabolism , AutophagyABSTRACT
Neuroendocrine tumors (NETs) are a type of rare tumor that can occur at multiple organs. Rectal NETs are the most common NETs in gastrointestinal tract. Due to the rarity of rectal NETs in rectal cancer, the molecular features and the correlation with patient therapeutic response and prognosis have not been investigated in detail. In this review, we focused on the molecular features, potential therapeutic targets and prognosis of rectal NETs. By summarizing the relevant studies, we established the mutational landscape of rectal NETs and identified a series of large fragment variations. Driver genes including TP53, APC, KRAS, BRAF, RB1, CDKN2A and PTEN were found as the top mutated genes. Large fragment alterations mainly involved known driver genes, including APC, TP53, CCNE1, MYC, TERT, RB1 and ATM. Germline mutations of APC, MUTYH, MSH6, MLH1 and MSH2 associated with Lynch syndrome or FAP were also found in rectal NETs. The BRAF-V600E mutation was reported as an actionable target in rectal NETs, and the combined BRAF/MEK inhibitors were found to be effective targeting BRAF-V600E in advanced or metastatic NETs. The known prognostic risk factors of rectal adenocarcinoma, including a series of demographic and clinicopathological factors were also prognostic factors for rectal NETs. Furthermore, three types of markers, including genetic alterations, protein expression levels and methylation, were also suggested as prognostic factors for rectal NETs. In summary, we established the landscape of mutations and large-fragment alterations of rectal NETs, and identified potential therapeutic targets and a series of prognostic factors. Future studies may focus on the optimization of therapeutic strategies based on potential actionable biomarkers.
Subject(s)
Neuroendocrine Tumors , Rectal Neoplasms , Humans , Proto-Oncogene Proteins B-raf/genetics , Rectal Neoplasms/genetics , Mutation , Prognosis , Biomarkers, TumorABSTRACT
Shiyang River Watershed is an important ecological barrier and agricultural production area in Northwest China, and the study of soil heavy metal content, distribution, and sources is important for agricultural product safety, pollution control, and ecosystem health. In this paper, 140 soil samples were collected from 28 stations to assess the level of heavy metal (Arsenic (As), Copper (Cu), Lead (Pb), Cadmium (Cd), Chromium (Cr), Mercury (Hg), Nickel (Ni), Zinc (Zn)) contamination, pollutant sources and influencing factors of soil in Shiyang River Watershed through determination of the metal contents and statistical analysis. The results indicated that the soils in the study area are typical saline soils in arid zones. The enrichment factors (EF) of As, Cr, Cu, Ni, Zn, and Pb indicate no contamination, and the EFs of Cd and Hg suggested minor contamination. Although the concentrations of Cd and Hg in soil are lower than others, they are more biotoxic and exhibit a moderate-high ecological risk. The index of geoaccumulation (Igeo) values reflect that most of the stations, especially the three groups of samples from depths of 10-20 cm, 20-40 cm, and 40-80 cm, are below the contamination threshold for all heavy metals. The chemical speciation of heavy metals, principal component analysis, and correlation analysis showed that Cr, Cu, Pb, Cd, Ni, and Zn mainly come from the natural accumulation upon weathering of soil-forming matrices. Hg and As mainly come from anthropogenic contributions. The effect of agricultural crop cultivation on soil heavy metal contamination is mainly through farm irrigation and crop-soil interactions, which accelerate the release of heavy metals through the weathering of soil-forming parent material and irrigation, which transports the heavy metals below the surface. The results of this study can provide a scientific basis for the involved authorities to formulate reasonable policies on environmental protection and pollution control.
ABSTRACT
Grazing is the dominant land use way for natural grasslands. Different grazing intensities could affect soil stoichiometry in grasslands by influencing the selective feeding by livestock, litter input, and microbial community structure. In this study, a grazing experiment was carried out in a grassland of agro-pastoral ecotone in Northern China for three years (2017-2019). The concentrations of total carbon (TC), total nitrogen (TN), dissolved organic carbon (DOC), dissolved nitrogen (DN), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) in soils were measured. We analyzed the stoichiometric characteristics of those parameters. The results showed that different grazing intensities (1, 2, 4 sheep·0.2 hm-2) had no significant effect on soil TC after three years. The moderate grazing intensity significantly reduced soil TN in 10-20 cm layer in 2019. The light, moderate, and heavy grazing intensities significantly increased soil C/N at 10-20 cm layer, while grazing intensities did not affect soil DOC, DN and DOC/DN. The soil DOC and DN content showed a decreasing trend with the increase of grazing intensity in 2019. It indicated that continuous high intensity grazing might reduce soil dissolved nutrients. The light grazing inten-sity increased soil MBC, while heavy grazing intensity reduced soil MBC significantly, with the increase of grazing year. Different grazing intensities did not affect soil MBN and MBC/MBN.