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Purpose: FKBP1A is a member of the immunophilin protein family, which participates in basic cellular processes involving cell proliferation and immunity, especially interacting with rapamycin drug and mTOR protein. However, the relation between FKBP1A and clinical characteristics in glioblastoma (GBM)patients remains to be explored. Methods HPA, Prognoscan and GEPIA2 databases were used for data mining and analyzing FKBP1A, its co-expressed genes and dendritic cell (DC) related markers. TIMER2.0 database was used for analyzing the correlation and prognosis of FKBP1A and DC cells infiltration level in GBM. Results For the first time, we found that up-regulated FKBP1A expression and its co-expressed genes RPN2, DDOST and ITGB1 were correlated with GBM patients’ worse survival. Then, the oncogenic gene FKBP1A correlated with abundant infiltration of DC cell in GBM, the increase of DC marker NRP1 expression was also mined to be significantly correlated with worse survival in GBM. FKBP1A might play a role in the biological activity of protein N-linked glycosylation among GBM tumor microenvironment. Conclusions These findings infer that FKBP1A and its associated DC cell infiltration are significantly potential novel malignant prognostic indicators for GBM.

SummaryPolymer flooding has been widely used to improve oil recovery. However, its effectiveness would be diminished when channels (e.g., fractures, fracture-like channels, void-space conduits) are present in a reservoir. In this study, we designed a series of particular sandwich-like channel models and tested the effectiveness and applicable conditions of micrometer-sized preformed particle gels (PPGs, or microgels) in improving the polymer-flooding efficiency. We studied the selective penetration and placement of the microgel particles, and their abilities for fluid diversion and oil-recovery improvement. The results suggest that polymer flooding alone would be inefficient to achieve a satisfactory oil recovery as the heterogeneity of the reservoir becomes more serious (e.g., permeability contrast kc/km > 50). The polymer solution would vainly flow through the channels and leave the majority of oil in the matrices behind. Additional conformance-treatment efforts are required. We tried to inject microgels in an attempt to shut off the channels. After the microgel treatment, impressive improvement of the polymer-flooding performance was observed in some of our experiments. The water cut could be reduced significantly by as high as nearly 40%, and the sweep efficiency and overall oil recovery of the polymer flood were improved. The conditions under which the microgel-treatment strategy was effective were further explored. We observed that the microgels form an external impermeable cake at the very beginning of microgel injection and prevent the gel particles from entering the matrices. Instead, the microgel particles could selectively penetrate and shut off the superpermeable channels under proper conditions. Our results suggest that the 260-µm microgel particles tested in this study are effective to attack the excessive-water-production problem and improve the oil recovery when the channel has a high permeability (>50 darcies). The gels are unlikely to be effective for channels that are less than 30 darcies because of the penetration/transport difficulties. After the gels effectively penetrate and shut off the superpermeable channel, the subsequent polymer solution is diverted to the matrices (i.e., the unswept oil zones) to displace the bypassed oil. Overall, this study provides important insights to help achieve successful polymer-flooding applications in reservoirs with superpermeable channels.

NRF2 is an important regulatory transcription factor involved in tumor immunity and tumorigenesis. In this study, we firstly identified that FKBP4/NR3C1 axis was a novel negative regulator of NRF2 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at protein level of NRF2 since it could not suppress the expression of NRF2 at mRNA level. Bioinformatics analysis and in vitro experiments further demonstrated that FKBP4 regulated NRF2 via regulating nuclear translocation of NR3C1. We then reported that naringenin, a flavonoid, widely distributed in citrus and tomato, could suppress autophagy and proliferation of BC cells through FKBP4/NR3C1/NRF2 signaling pathway in vitro and in vivo. Naringenin was also found to promote dendritic cell (DC) differentiation and maturation through FKBP4/NR3C1/NRF2 axis. Therefore, our study found that naringenin could induce inhibition of autophagy and cell proliferation in BC cells and enhance DC differentiation and maturation, at least in part, though regulation of FKBP4/NR3C1/NRF2 signaling pathway. Identification of FKBP4/NR3C1/NRF2 axis would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.

Background TMEM173 is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits cGAS related signals that activate host innate immune responses. It has also been found to be involved in tumor immunity and tumorigenesis. Methods Bc-GenExMiner, PROMO and STRING database were used for analyzing clinical features and interplays of FKBP4, TMEM173 and NR3C1. Transient transfection, western blotting, quantitative real-time PCR, luciferase reporter assay, immunofluorescence and nuclear and cytoplasmic fractionation were used for regulation of FKBP4, TMEM173 and NR3C1. Both knockdown and overexpression of FKBP4, TMEM173 and NR3C1 were used to analyze effects on autophagy and proliferation of breast cancer (BC) cells. Flow cytometry analysis, cytokine analysis and exosome isolation and identification were utilized to test tumor-infiltrating dendritic cell (TIDC) maturation. Results In this study, we firstly identified that FKBP4/NR3C1 axis was a novel negative regulator of TMEM173 in BC cells. The effect of FKBP4 appeared to be at the transcriptional level of TMEM173 since it could suppress the promoter activity of TMEM173, thereby affecting TMEM173 at mRNA and protein levels. Bioinformatics and in vitro experiments further demonstrated that FKBP4 regulated TMEM173 via regulating nuclear translocation of NR3C1. We then reported that naringenin, a flavonoid, could enhance autophagy and suppress proliferation of BC cells through the induction of TMEM173 in vitro and in vivo. Naringenin was also found to promote TIDC maturation through FKBP4/NR3C1/TMEM173 axis of both BC cells exosome and DC itself. Conclusion We demonstrated that naringenin could induce cell proliferation inhibition and cytoprotective autophagy of BC cells and enhance TIDC maturation, at least in part, though regulation of FKBP4/NR3C1/TMEM173 signaling pathway. Identification of FKBP4/NR3C1 axis as a novel TMEM173 regulator would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.

Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. In current study, 11 DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. Four hundred and eighty two predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top 20 lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients' overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. Three hundred and twenty target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the topest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients' OS.

Oil-in-water (o/w) Pickering emulsions stabilized by polyacrylamide (PAM) and poly(acrylamide-co-acrylic acid) nano-sized crosslinked polymeric particles (nanogels) under various conditions are described herein. Nanogels with different crosslinking and charge degree were synthesized through suspension polymerization and characterized at various salinities and pH using dynamic light scattering (DLS) and scanning electron microscopy (SEM). The PAM nanogel-stabilized o/w Pickering emulsions were quickly demulsified in alkaline solutions whereas they showed markedly stability in brines and under acidic conditions. A small amount of nanogels were sufficient for the formation of Pickering emulsions. The average diameter of oil droplets was no longer decreasing with nanogel concentration increment above 1000 mg/L. In addition, the average diameter of oil drops was independent of sonication period in the range of 15–240 s. Interestingly, the string-like structures of nanogel aggregations were found in the aromatic hydrocarbons/water Pickering emulsions, which significantly enhanced the emulsion stability. Compared to the crude oil, the corresponding Pickering emulsions showed excellent flowability at various shear rates. The crude oil/water Pickering emulsions could be broken using alkali as a trigger, which suggests the potential utility for the recovery of crude oil.

Nicotine has been found to induce the proliferation of lung cancer cells through tumor invasion and to confer resistance to apoptosis. Periostin is abnormally highly expressed in lung cancer and is correlated with angiogenesis, invasion and metastasis. Here, we investigated the roles of periostin in the lung cancer cell proliferation, drug resistance, invasion and epithelial-mesenchymal transition (EMT) induced by nicotine. The periostin gene was silenced using small interfering RNA (siRNA) in A549 non-small cell lung cancer (NSCLC) cells. The cells were transfected with control or periostin siRNA plasmids. Periostin mRNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cell proliferation was detected using the MTT assay and cell apoptosis was detected by Annexin V-FITC and propidium iodide (PI) double staining. Tumor invasion was detected by the Boyden chamber invasion assay. Western blotting was performed to detect the expression of the EMT marker Snail. Our results revealed that stably periostin-silenced cells were acquired by G418 screening, and the periostin mRNA expression levels of which were decreased by nearly 80%. Periostin-silenced A549 cells exhibited reduced cell proliferation, elevated sensitivity to chemotherapy with cisplatin, decreased cell invasion and Snail expression (P

The prognosis is extremely poor for patients with brain metastases in recursive partitioning analysis (RPA) class 3. It is not clear whether dose elevation for brain lesions in addition to whole-brain radiotherapy could improve survival for those patients. This study aimed to assess the efficacy and safety of dose elevation with intensity-modulated radiation therapy (IMRT) for patients with 1 to 3 brain metastases in RPA class 3. From January 2013 to December 2015, 24 patients with 1 to 3 brain metastases in RPA class 3 were included in this study. The median age was 60 (range 41–85) years and the mean graded prognostic assessment (GPA) score was 1.25 (range 0.5–2). Whole-brain radiotherapy (30 Gy) with a simultaneous integrated boost (SIB) to the brain metastases (totaling 40 Gy) was delivered in 10 fractions using IMRT technique. Survival times and overall safety were assessed. The significance of prognostic variables on survival was assessed by both univariate and multivariate analyses. All of the patients completed the planned SIB schedule. The overall response rate was 66.7%. The median survival time (MST) was 8 months for the entire group of patients. The MST was 5 months for patients with a GPA score of 0.5 to 1 (n = 11 patients) and 12 months with a GPA score of 1.5 to 2 (n = 13 patients). No acute or late toxicities greater than grade 2 were detected. Age and subsequent chemotherapy were significantly associated with MST on univariate and multivariate analyses. It is feasible to elevate radiation doses to 40 Gy using the IMRT technique in RPA class 3 patients with 1 to 3 brain metastases without serious toxicities. The preliminary results are encouraging and further studies with larger cohorts are warranted.