Link between miR-19b and the mTOR signaling pathway in cancer prognosis

Objective Previous studies have reported differing conclusions regarding the prognostic value of miR-19b in cancers.Moreover,miR-19b may affect tumor growth by different pathways,mainly targeting PTENPI3K-AKT,which activates the downstream mTOR pathway.Therefore,we performed data mining to explore the possible correlation between miR-19b and mTOR in cancer prognosis.Methods We conducted online search and collected a total of 943 articles.According to different authors cross check and our study including/excluding criteria we at end retained 21 articles with 25 studies in this meta-analysis.Then TCGA data containing miR-19b level with cancer progression were obtained using OncomiR.Furthermore,Trial Sequential Analysis(TSA)was performed to determine whether the results of our meta-analysis could be used in clinical applications.After that,articles regarding the mechanism of miR-19b in various cancers were analyzed and KEGG pathway database was used to find the main regulatory function of miR-19b in human cancers.Results Overall hazard ratio(HR)results showed that higher levels of miR-19b expression were correlated with shorter overall survival time[HR=1.54,95%confidence interval(CI)=1.20-1.98]by promoting distant metastasis,but had no correlation with disease-free survival(DFS)/progression-free survival(PFS;HR=0.61,95%CI=0.31–1.19).Data from The Cancer Genome Atlas also revealed the role of miR-19b in tumorigenesis.According to trial sequential analysis results,more evidence is required to confirm that miR-19b is not correlated with DFS/PFS.Exploration of the mechanism revealed a possible link between miR-19b and the mTOR pathway.Conclusion miR-19b may have a pro-carcinogenic role through the mTOR pathway and thus,it is likely to be a therapeutic target for cancers.

Prognostic factors for pN2 non-small cell lung cancer:a comprehensive evidence from 73 studies involving 23,772 patients

Obojective Non-small-cell lung cancer(NSCLC)is a common malignancy.pN2 NSCLC,with pathologically confirmed ipsilateral mediastinal/subcarinal nodes metastasis,has been known as a very heterogeneous subgroup in terms of its anatomical,biological and patient characteristics.Prognostic factors based on patient characteristics were not well determined yet in this subgroup,and there is currently no standard treatment recommendation for these heterogeneous pN2 subjects.Apparent disagreements and inconsistency exist in study reports concerning the prognostic significance of certain factors in pN2 NSCLC,especially regarding to the issue about whether skip N2 metastasis benefit from surgery.Methods We therefore performed this comprehensive summary of the published literatures to draw a more precise and less uncertain conclusion.After a comprehensive literature search,a total of 73 studies involving 23,773 subjects were included according to eligibility criteria.Results As expected,most of the investigated factors,such as old age,male,advanced pathological T stage,advanced clinical N stage,multiple N2 stations,extended surgical resection(pneumonectomy),and incomplete resection,but not post-operation treatment(eg.chemotherapy and radiotherapy)were significantly associated with poor survival.However,skip N2 metastasis was favourable prognostic factors in operable pN2 NSCLC subjects.Other factors(histological type and primary tumour side)were neutral in terms of association with overall survival.We highlighted a number of important prognostic factors for pN2 NSCLC patients.Particularly,patients with skip N2 disease benefit from surgery.Conclusion Our findings could be used as reference information for decision-making in clinical practice and future study design.

The possible value of ~18F-FDG positron emission tomography/computerized tomography imaging in detection of atherosclerotic plaque

Objective：To evaluate the clinical value with positron emission tomography/computerized tomography（PET/CT） imaging for the detection of vulnerable plaque in atherosclerotic lesions. Methods：Sixty people with a age of over 60[mean age （69.2 ± 7.1）years] underwent three dimension（3D） whole-body fluorine-18-2-fluoro-2-deoxy-D-glucose（^18F-FDG） PET/CT imaging and were evaluated retrospectively, including 6 cases assessed as normal and 54 cases with active atherosclerotic plaque. Fifty-four cases with SUVs and CT values in the aortic wall of high-FDG-uptake were measured retrospectively. These high-FDG-uptake cases in the aortic wall were divided into three groups according their CT value. Cases in group 1 had high uptake in atherosclerotic lesions of the aortic wall with CT value of less than 60 Hu（soft plaque）. Cases in group 2 had high uptake with CT value between 60-100 Hu （intermediate plaque）, Cases in group 3 had high uptake with CT value more than 100 Hu（calcified plaque）, Group 4 was normal. Results： In group 1, there were 42 high-FDG-uptake sites （average SUV 1.553 ± 0.486）. In group 2, there were 30 high-FDG-uptake sites（average SUV 1.393 ± 0.296）. In group 3, there were 36 high-FDG-uptake sites（average SUV 1.354 ± 0.189）. In group 4, there were 33 normal-FDG-uptake sites （average SUV was 1.102 ± 0.141）, The SUVs showed significant difference among the four groups（F = 678.909, P = 0.000）. There were also significant difference found between the normal-FDG-uptake group and the high-FDG-uptake groups（P = 0.000, 0.000, 0.001, respectively）. Conclusion：Different degrees of ^18F-FDG uptake in active large atherosclerotic plaque were shown in different stages of atherosclerotic plaque formation. The soft plaque had the highest FDG uptake in this study. This suggested that ^18F- FDG PET/CT imaging may be of great potential value in early diagnosis and monitoring of vulnerable soft plaque in atherosclerotic lesions.

BaTiO_(3)@Au nanoheterostructure suppresses triple-negative breast cancer by persistently disrupting mitochondrial energy metabolism

Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity,resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment.To address these limitations,here we developed a robust pyroelectric BaTiO_(3)@Au core–shell nanostructure(BTO@Au)to selectively and persistently block energy generation of tumor cells.Stimulated by near-infrared(NIR)laser,the Au shell could generate heat to activate the BaTiO_(3)core to produce reactive oxygen species(ROS)regardless of the constrained microenvironment,thus prominently inhibits mitochondrial oxidative phosphorylation(OXPHOS)and reduces ATP production to induce TNBC cell apoptosis.The therapeutic effects have been well demonstrated in vitro and in vivo,paving a new way for the development of metabolic interventions.

Polydopamine and ammonium bicarbonate coated and doxorubicin loaded hollow cerium oxide nanoparticles for synergistic tumor therapy

The development of effective nanoplatforms is extremely necessary for cancer therapy.Herein,we prepared polydopamine(PDA)andammonium bicarbonate(NH4HCO3)coated and doxorubicin(Dox)loaded hollow cerium oxide(CeO2)NPs(PDAC NPs),which showedexcellent synergistic effect for photothermal therapy,chemotherapy and chemodynamic therapy.Under near infrared laser irradiation,PDA shell could absorb the incident light and convert it into heat,which could not only kill tumor cells with hyperthermia,but also trigger thedecomposition of NH4HCO3 into gaseous carbon dioxide and ammonia,leading to the destroy of PDA shell.The leakage of PDA furtheraccelerated Dox release and exposed CeO2 surface,in which Dox could enter into cell nucleus to induce chemotherapy,and CeO2 couldcatalyze cellular hydrogen peroxide into hydroxyl radical to present chemodynamic therapy.In fact,PDAC NPs showed an excellenttherapeutic efficacy both in vitro and in vivo.This design provides a new strategy for synergistic tumor therapy.

Crystallographic facet-dependent stress responses by polyhedral lead sulfide nanocrystals and the potential ＂safe-by-design＂ approach

The particular physicochemical properties of nanomaterials are able to elicit unique biological responses. The property activity relationship is usually established for in-depth understanding of toxicity mechanisms and designing safer nanomaterials. In this study, the toxic role of specific crystallographic facets of a series of polyhedral lead sulfide （PbS） nanocrystals, including truncated octahedrons, cuboctahedrons, truncated cubes, and cubes, was investigated in human bronchial epithelial cells （BEAS-2B） and murine alveolar macrophages （RAW 264.7） cells./100} facets were found capable of triggering facet-dependent cellular oxidative stress and heavy metal stress responses, such as glutathione depletion, lipid peroxidation, reactive oxygen species （ROS） production, heme oxygenase-1 （HO-1） and metallothionein （MT） expression, and mitochondrial dysfunction, while {111} facets remained inert under biological conditions. The {100}-facet-dependent toxicity was ascribed to {100}-facet-dependent lead dissolution, while the low lead dissolution of {111} facets was due to the strong protection afforded by poly（vinyl pyrrolidone） during synthesis. Based on this facet-toxicity relationship, a ＂safe-by-design＂ strategy was designed to prevent lead dissolution from {100} facets through the formation of atomically thin lead-chloride adlayers, resulting in safer polyhedral PbS nanocrystals.

Superfluid-superradiant mixed phase of the interacting degenerate Fermi gas in an optical cavity

We investigate the ground-state properties of an attractively interacting degenerate Fermi gas coupling with a high-finesse optical cavity. We predict a new mixed phase with both the superfluid and superradiant properties for the intermediate fermion-fermion interaction and fermion-photon coupling strengths. Moreover, in this mixed phase a relatively large ratio of the scaled polarization to the dimensionless mean-field gap, which is in contrast to that in the conventional superfluid regime can be obtained. We also figure out rich phase diagrams depending crucially on the atomic resonant frequency(effective Zeeman field) and address briefly the experimental detection of our predicted quantum phases.