Extracellular adenosine triphosphate (ATP) and its receptor, P2X7 receptor (P2X7R), are playing an important role in the pathological process of renal ischemia-reperfusion injury, but their ...underlying mechanism remains unclear. Also, the effects of tubular epithelium-expressed P2X7 receptor on ischemia acute kidney injury is still unknown. The aim of this study is to clarify if this mechanism involves the activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the renal tubular epithelial cells. In our research, we used male C57BL/6 wild type and P2X7R (-/-) mice, cultured human proximal tubular epithelial cells, and kidneys from acute kidney injury patients. Mice underwent for unilateral nephrectomy combined with the lateral renal pedicle clamping. Cultured cells were subjected to hypoxia/reoxygenation or ATP. Apyrase and A438079 were used to block the extracellular ATP/P2X7 receptor pathway. We also constructed radiation-induced bone marrow (BM) chimeras by using P2X7R (-/-) mice and P2X7R (+/+) wild-type mice. P2X7 receptor deficiency protected from renal ischemia-reperfusion injury and attenuated the formation of NLRP3 inflammasome. By using BM chimeras, we found a partial reduction of serum creatinine and less histological impairment in group wild-type BM to P2X7R (-/-) recipient, compared with group wild-type BM to wild-type recipient. In renal tubular epithelial cells, hypoxia/reoxygenation induced ATP release and extracellular ATP depletion reduced the expression of active IL-1β. ATP activated the NLRP3 inflammasome in renal tubular epithelial cells, which were blunted by transient silence of P2X7 receptor, as well as by P2X7 receptor blocking with A438079. In human samples, we found that patients with Stage 3 AKI had higher levels of P2X7 receptor expression than patients with Stage 1 or Stage 2. Extracellular ATP/P2X7 receptor axis blocking may protect renal tubular epithelial cells from ischemia-reperfusion injury through the regulation of NLRP3 inflammasome.
Resistance to TKI treatment is a major obstacle in effective treatment of NSCLC. Besides EGFR mutation status, the mechanisms involved are largely unknown. Some evidence supports a role for microRNA ...21 in modulating drug sensitivity of chemotherapy but its role in NSCLC TKI resistance still remains unexplored. This study aimed to investigate whether NSCLC miR-21 mediated resistance to TKIs also results from Pten targeting. Here, we show miR-21 promotes cancer by negatively regulating Pten expression in human NSCLC tissues: high miR-21 expression levels were associated with shorter DFS in 47 NSCLC patients; high miR-21/low Pten expression levels indicated a poor TKI clinical response and shorter overall survival in another 46 NSCLC patients undergoing TKI treatment. In vitro assays showed that miR-21 was up-regulated concomitantly to down-regulation of Pten in pc-9/GR cells in comparison with pc-9 cells. Moreover, over-expression of miR-21 significantly decreased gefitinib sensitivity by down-regulating Pten expression and activating Akt and ERK pathways in pc-9 cells, while miR-21 knockdown dramatically restored gefitinib sensitivity of pc-9/GR cells by up-regulation of Pten expression and inactivation of AKT and ERK pathways, in vivo and in vitro. We propose alteration of miR-21/Pten expression as a novel mechanism for TKI resistance in NSCLC cancer. Our findings provide a new basis for using miR 21/Pten-based therapeutic strategies to reverse gefitinib resistance in NSCLC.
The prognostic value of elevated pretreatment platelet counts remains controversial in lung cancer patients. We performed the present meta-analysis to determine its precise role in these patients.
We ...employed a multiple search strategy in the PubMed, EMBASE and Cochrane Library databases to identify eligible studies. Disease-free survival (DFS)/progression-free survival (PFS)/time to progression (TTP) and overall survival (OS) were used as outcomes with hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity among the studies and publication bias were also evaluated.
A total of 40 studies including 16,696 lung cancer patients were eligible for the analysis. Overall, the pooled analysis showed that compared with normal platelet counts, elevated pretreatment platelet counts were associated with poorer OS (HR = 1.54, 95% CI: 1.37-1.72, P < 0.001) and poorer DFS/PFS/TTP (HR = 1.62, 95% CI: 1.33-1.98, P < 0.001) in patients with lung cancer. In subgroup analyses, elevated pretreatment platelet counts were also associated with poorer OS and DFS/PFS/TTP in most subgroups. There was no evidence of publication bias.
This meta-analysis revealed that elevated pretreatment platelet counts were an independent predictor of OS and DFS/PFS/TTP in lung cancer patients. Large-scale prospective studies and a validation study are warranted.
The high nutritional value of alfalfa hay makes it a widely utilized component in animal feed. However, the current prevalent drying methods for forage have a significantly detrimental impact on the ...quality of alfalfa during the drying process. This study investigates the effects of high-voltage corona discharge (HVCD) treatment on post-cut alfalfa. Gradient experiments are conducted by adjusting the air-gap spacing at a voltage of 25 kV. The results demonstrate that as the distance decreases, there is an observed increase in the drying rate, rehydration rate, and color intensity of the HVCD-treated material. HVCD treatment significantly enhances crude protein content, which increases with decreasing air-gap spacing. Meanwhile, it negatively affects lignin, neutral detergent fiber (NDF), and acid detergent fiber (ADF) levels. The relative forage quality (RFQ) of alfalfa reaches its peak at an air-gap spacing of 7 cm. The application of HVCD disrupts the fiber structure and induces significant electroporation effects in cells. Minimal changes in functional groups preserve nutrient integrity. Furthermore, HVCD exhibits lower energy consumption compared to hot air dryers. The HVCD treatment is a highly efficient and effective method, with a gradual improvement in alfalfa hay quality as the air-gap distance decreases.
Background/Aims: LncRNA EGFR-AS1 is an antisense transcript of EGFR, which plays a key role in gastric cancer progression. This study was aimed to explore the effects of lncRNA EGFR-AS1 on GC and the ...underling mechanisms. Methods: The silencing of EGFR-AS1 expression was performed by using EGFR-AS1 shRNA lentivirus in MGC803 and SGC-7901 GC cell. The levels of lncRNA EGFR-AS1 and EGFR were detected by qPCR and western blot. Cell proliferation was assessed by CCK-8, EdU, and colony formation assays. The EGFR mRNA stability was explored by using RNA synthesis inhibitor α-amanitin. Results: In our study, EGFR-AS1 significantly up-regulated in GC tissues and correlated with tumor size. And the expression of EGFR-AS1 positively correlated with EGFR in tissues. Moreover, knock-down of EGFR-AS1 inhibited the proliferation of GC cells via suppressing EGFR-dependent PI3K/AKT pathway in vitro and in vivo. Mechanismly, depletion of EGFR-AS1 was found to decrease EGFR expression by reduction of EGFR mRNA stability. Conclusion: Our findings suggested that EGFR-AS1 might have an oncogenic effect on GC and serve as a potential target of GC.
Background/Aims: Autophagy is a dynamic catabolic process that maintains cellular homeostasis. Whether it plays a role in promoting cell survival or cell death in the process of renal ...ischemia/reperfusion (I/R) remains controversial, partly because renal autophagy is usually examined at a certain time point. Therefore, monitoring of the whole time course of autophagy and apoptosis may help better understand the role of autophagy in renal I/R. Methods: Autophagy and apoptosis were detected after mice were subjected to bilateral renal ischemia followed by 0-h to 7-day reperfusion, exposure of TCMK-1 cells to 24-h hypoxia, and 2 to 24-h reoxygenation. The effect of autophagy on apoptosis was assessed in the presence of autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin. Results: Earlier than apoptosis, autophagy increased from 2-h reperfusion, reached the maximum at day 2, and then began declining from day 3 when renal damage had nearly recovered to normal. Exposure to 24-h hypoxia induced autophagy markedly, but it decreased drastically after 4 and 8-h reoxygenation, which was accompanied with increased cell apoptosis. Inhibition of autophagy with 3-MA increased the apoptosis of renal tubular cells during I/R in vivo and hypoxia/reoxygenation (H/R) in vitro. In contrast, activation of autophagy by rapamycin significantly alleviated renal tissue damage and tubular cell apoptosis in the two models. Conclusion: Autophagy was induced in a time-dependent manner and occurred earlier than the onset of cell apoptosis as an early response that played a renoprotective role during renal I/R and cell H/R. Up-regulation of autophagy may prove to be a potential strategy for the treatment of acute kidney injury.
Over the past decades, because of large-scale bensulfuron-methyl (BSM) application, environmental residues of BSM have massively increased, causing severe toxicity in rotation-sensitive crops. The ...removal of BSM from the environment has become essential. In this study, the combined bioremediation of the arbuscular mycorrhizal fungi (AMF)
and BSM-degrading strain
S113 of BSM-polluted soil was investigated. BSM degradation by S113 in the maize rhizosphere could better promote AMF infection in the roots of maize, achieving an infection rate of 86.70% on the 36th day in the AMF + S113 + BSM group. Similarly, AMF enhanced the colonization and survival of S113 in maize rhizosphere, contributing 4.65 × 10
cells/g soil on the 15th day and 3.78 × 10
cells/g soil on the 20th day to a population of colonized-S113 (based possibly on the strong root system established by promoting plant-growth AMF). Both S113 and AMF coexisted in rhizosphere soil. The BSM-degrading strain S113 could completely remove BSM at 3 mg/kg from the maize rhizosphere soil within 12 days. AMF also promoted the growth of maize seedlings. When planted in BSM-contaminated soil, maize roots had a fresh weight of 2.59 ± 0.26 g in group S113 + AMF, 2.54 ± 0.20 g in group S113 + AMF + BSM, 2.02 ± 0.16 g in group S113 + BSM, and 2.61 ± 0.25 g in the AMF group, all of which exceeded weights of the control group on the 36th day except for the S113 + BSM group. Additionally, high-throughput sequencing results indicated that simultaneous inoculation with AMF and strain S113 of BSM-polluted maize root-soil almost left the indigenous bacterial community diversity and richness in maize rhizosphere soil unaltered. This represents a major advantage of bioremediation approaches resulting from the existing vital interactions among local microorganisms and plants in the soil. These findings may provide theoretical guidance for utilizing novel joint-bioremediation technologies, and constitute an important contribution to environmental pollution bioremediation while simultaneously ensuring crop safety and yield.
HE4 expression in lung cancer, a meta-analysis Zhong, Hai; Qian, Yingying; Fang, Surong ...
Clinica chimica acta,
July 2017, 2017-Jul, 2017-07-00, 20170701, Letnik:
470
Journal Article
Recenzirano
The prognostic role of Human epididymis protein 4 (HE4) expression in lung cancer remains controversial. We performed this meta-analysis to assess the prognostic value of HE4 expression in lung ...cancer.
A systematic literature search was conducted to identify eligible studies in PubMed, Embase and Wanfang databases. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to assess the relationship.
A total of 1412 patients from 8 studies were included in this meta-analysis. The results of univariate analysis (HR=1.73, 95% CI: 1.19–2.52, P=0.004) and multivariate analysis (HR=2.49, 95% CI: 1.89–3.28, P<0.001) demonstrated that high HE4 expression in lung cancer patients was correlated with poor overall survival (OS). We observed through further stratified analysis of the results of the univariate analysis that high HE4 expression was associated with worse OS in Asian lung cancer patients (HR=2.48, 95% CI: 1.88–3.26, P<0.001). However, there was no significant association between high HE4 expression and poor OS in Caucasian patients (HR=1.12, 95% CI: 0.80–1.55, P=0.513).
High serum HE4 level was a marker of poor prognosis in lung cancer patients, particularly in Asian patients with lung cancer.
•A meta-analysis assessed high HE4 expression associated with overall survival in lung cancer patients.•A total of 1412 patients from 8 studies were included in this meta-analysis.•High serum HE4 level was a marker of poor prognosis in lung cancer patients, particularly in Asian patients with lung cancer.
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