MiRNAs are important regulators of different biological processes, including tumorigenesis. MiR-210 is a potential prognostic factor for survival in patients with cancer according to previous ...clinical researches. We conducted a systematic review and meta-analysis to summarize the significance of increased miR-210 expression in the prognosis of indicated cancers.
The present systematic review and meta-analysis of 16 researches included 1809 patients with 7 different types of cancers from 7 countries, and aimed to explore the association between miR-210 expression and the survival of cancer patients. Over-expression of miR-210 may predict poor overall survival (OS, HR = 1.33, 95% CI: 0.85-2.09, P = 0.210), but the effect was not significant. While the predictive effect on disease-free survival (DFS, HR = 1.89, 95% CI: 1.30-2.74, P = 0.001), progression-free survival (PFS, HR = 1.20, 95% CI: 1.05-1.38, P = 0.007) and relapse-free survival(RFS, HR = 4.42, 95% CI: 2.14-9.15, P = 0.000) for patients with breast cancer, primary head and neck squamous cell carcinoma (HNSCC), renal cancer, soft-tissue sarcoma, pediatric osteosarcoma, bladder cancer or glioblastoma was certain. Subgroup analysis showed the limited predictive effect of over-expressed miR-210 on breast cancer OS (HR = 1.63, 95% CI: 0.47-5.67, P = 0.443), breast cancer DFS (HR = 2.03, 95% CI: 0.90-4.57, P = 0.088), sarcoma OS (HR = 1.24, 95% CI: 0.20-7.89, P = 0.818) and renal cancer OS (HR = 1.16, 95% CI: 0.27-4.94, P = 0.842).
This systematic review and meta-analysis suggests that miR-210 has a predictive effect on survival of patients with studied cancer types as indexed by disease-free survival, progression-free survival and relapse-free survival. While the predictive effect on overall survival, breast cancer overall survival, breast cancer disease-free survival, sarcoma overall survival and renal cancer overall survival was not statistically significant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The mechanism of the clustering in Al-Mg-Si-Cu alloys has been a long-standing controversial issue. Here, for the first time, the mechanism of the clustering in the alloy was investigated by a ...Kinetic Monte Carlo (KMC) approach. In addition, reversion aging (RA) was carried out to evaluate the simulation results. The results showed that many small-size clusters formed rapidly in the early stages of aging. With the prolongation of aging time, the clusters merged and grew. The small clusters formed at the beginning of aging in Al-Mg-Si-Cu alloy were caused by initial vacancies (quenching vacancies). The merging and decomposition of the clusters were mainly caused by the capturing of vacancies, and the clusters had a probability to decompose before reaching a stable size. After repeated merging and decomposition, the clusters reach stability. During RA, the complex interaction between the cluster merging and decomposition leaded to the partial irregular change of the hardness reduction and activation energy.
It has been confirmed that mitochondrial impairment may underlie both sporadic and familial Parkinson’s disease (PD). Mitochondrial fission/fusion and biogenesis are key processes in regulating ...mitochondrial homeostasis. Therefore, we explored whether the protective effect of resveratrol in rotenone-induced neurotoxicity was associated with mitochondrial fission/fusion and biogenesis. The results showed that resveratrol could not only promote mitochondrial mass and DNA copy number but also improve mitochondrial homeostasis and neuron function in rats and PC12 cells damaged by rotenone. We also observed effects with alterations in proteins known to regulate mitochondrial fission/fusion and biogenesis in rotenone-induced neurotoxicity. Therefore, our findings suggest that resveratrol may prevent rotenone-induced neurotoxicity through regulating mitochondrial fission/fusion and biogenesis.
Alloys meeting the requirements of “700 °C and above” advanced ultra-super-critical technology, with higher thermal efficiency, have been developed in recent years. Here, a new wrought Ni-based ...superalloy with excellent high-temperature creep strength based on Waspaloy has been developed and is proposed as a candidate material for application in 700 °C class advanced ultra-super-critical steam turbine blades. In this new alloy, the Molybdenum (Mo) in Waspaloy is partially replaced by Tungsten (W). Creep tests have shown that this new Ni-based alloy has a 70 MPa higher creep-rupture strength than that of Waspaloy at 700 °C by extrapolating the experimental data. Detailed creep-rupture mechanisms have been analyzed by means of scanning electron microscopy, transmission electron microscopy, and chemical phase analysis with a view to devising potential approaches for performance improvements. The results showed that the partial replacement of Mo by W had negligible effect on the composition of carbides precipitated in the alloy. Instead, the amount of the γ′ phase was significantly increased, and mismatch between the γ and γ′ phases was reduced. In this way, the stability of the γ′ phase was increased, its coarsening rate was reduced, and its critical shear stress was increased. As a result, the high-temperature creep-fracture strength of the new alloy was increased.
In this study, based on the sensitivity of the chemical composition fluctuation to the thermodynamic parameter, which controls the level of the stacking fault energy (SFE), a series of high Cr–Mn–N ...twinning-induced plasticity (TWIP) stainless steels are designed by using a sublattice model, and their mechanical properties and micro deformation mechanism are analyzed The formation of mechanical twins (Mts) during the deformation makes the test steel show a perfect combination of strength and ductility after different solution treatments. Among them, after a solution treatment at 950 °C and 1050 °C, the 19Cr–0.7N and 19CrSi–0.7N samples have the maximum value with the product of the strength and plasticity reaching 60.7% and 64.6%, and 12Cr–CN has the maximum value after the solution treatment at 1200 °C, reaching 81.3%. The SFE values of the 19Cr–0.7N and 19CrSi–0.7N samples were relatively high, 48 mJ·m−2 and 45 mJ·m−2, respectively. The SFE of 12Cr–CN is 37 mJ·m−2, and the Mts grow rapidly during the deformation and maintain the highest twinning density under the same strain conditions. The characterization of the tensile samples occurs under different deformations by electron backscattered diffraction (EBSD) and transmission electron microscope (TEM). The results of the EBSD local misorientation difference angle analysis showed the Silicon element addition with a good Mts saturation rate. It is observed from the TEM that the nucleation process of the Mts with a high SFE is difficult, and the Mts emit and grow inward along the grain boundary during the tensile process and present a cross shape with the increase in strain. The contribution of the grain boundary strengthening (σ0), dislocation strengthening (σf), and twinning strengthening effect (σt) under dynamic micro-refinement to stress were calculated. It is known that under a certain amount of strain, the ratio of σt and σf changes with increasing, and when the contribution of the twinning deformation to the stress exceeds about 25%, the reinforcement of the plastic deformation is dominated by the plane of σf.
Nitrogen mustard (NM) causes severe skin injury with an obvious inflammatory response, which is lack of effective and targeted therapies. Vitamin D3 (VD3) has excellent anti‐inflammatory properties ...and is considered as a potential candidate for the treatment of NM‐induced dermal toxicity; however, the underlying mechanisms are currently unclear. Cyclooxygenase‐2 (COX2; a widely used marker of skin inflammation) plays a key role in NM‐induced cutaneous inflammation. Herein, we initially confirmed that NM markedly promoted COX2 expression in vitro and in vivo. NM also increased NOD‐like receptor family pyrin domain containing 3 (NLRP3) expression, caspase‐1 activity, and interleukin‐1β (IL‐1β) release. Notably, treatment with a caspase‐1 inhibitor (zYVAD‐fmk), NLRP3 inhibitor (MCC950), and NLRP3 or caspase‐1 siRNA attenuated NM‐induced NLRP3 inflammasome activation, with subsequent suppression of COX2 expression and IL‐1β release in keratinocytes. Meanwhile, NM increased mitochondrial reactive oxygen species (mtROS) and decreased manganese superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) activities. Mito‐TEMPO (a mtROS scavenger) ameliorated NM‐caused NLRP3 inflammasome activation in keratinocytes. Moreover, VD3 improved SIRT3 and SOD2 activities, decreased mtROS contents, inactivated the NLRP3 inflammasome, and attenuated cutaneous inflammation induced by NM in vitro and in vivo. The beneficial activity of VD3 against NM‐triggered cutaneous inflammation was enhanced by the inhibitors of IL‐1, mtROS, NLRP3, caspase‐1, and NLRP3 or caspase‐1 siRNAs, which was abolished in SIRT3 inhibitor or SIRT3 siRNA‐treated keratinocytes and skins from SIRT3−/− mice. In conclusion, VD3 ameliorated NM‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome, which was partially mediated through the SIRT3–SOD2–mtROS signaling pathway.
Vitamin D3 (VD3) has excellent anti‐inflammatory properties and is considered as a potential candidate for the treatment of nitrogen mustard (NM)‐induced dermal toxicity; however, the underlying mechanisms are currently unclear. In the present study, we found that VD3 ameliorated NM‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome, which was partially mediated through the SIRT3–SOD2–mtROS signaling pathway. These results provide a new molecular mechanism of VD3 that might be utilized for the treatment of NM‐induced dermal toxicity.
AlCrFeNiMoNb high-entropy alloys were successfully coated onto a ZM5 alloy using high-velocity air fuel spray (HVAF). Microcomputed tomography(micro-CT) results revealed that the porosity of the ...coating was only 0.36%, which demonstrates the coating has a highly dense structure. The average microhardness of high-entropy alloys coating was ＞ 5 times greater than that of the ZM5 alloy substrate. The changes of ZM5 substrate microhardness can be attributed to dynamic recrystallisation. The corrosion potential (Ecorr) of the AlCrFeNiMoNb coating was improved to approximately∼ − 0.998 V and the corrosion current (Icorr) of the coating significantly decreased by two orders of magnitude. The wear volume loss of the coating was ∼15 times lower than that of the ZM5 substrate. This indicates that the coating of the AlCrFeNiMoNb high-entropy alloy on the ZM5 substrate significantly improved the wear resistance of the ZM5 alloy. The ZM5 alloy surface had better corrosion and wear resistance properties owing to the protection offered by the AlCrFeNiMoNb high-entropy alloy.
Nitrogen mustard (NM) causes severe vesicating skin injury, which lacks effective targeted therapies. The major limitation is that the specific mechanism of NM-induced skin injury is not well ...understood. Recently, autophagy has been found to play important roles in physical and chemical exposure-caused cutaneous injuries. However, whether autophagy contributes to NM-induced dermal toxicity is unclear. Herein, we initially confirmed that NM dose-dependently caused cell death and induced autophagy in keratinocytes. Suppression of autophagy by 3-methyladenine, chloroquine, and bafilomycin A1 or ATG5 siRNA attenuated NM-induced keratinocyte cell death. Furthermore, NM increased transient receptor potential vanilloid 1 (TRPV1) expression, intracellular Ca
content, and the activities of Ca
/calmodulin-dependent kinase kinase β (CaMKKβ), AMP-activated protein kinase (AMPK), unc-51-like kinase 1 (ULK1), and mammalian target of rapamycin (mTOR). NM-induced autophagy in keratinocytes was abolished by treatment with inhibitors of TRPV1 (capsazepine), CaMKKβ (STO-609), AMPK (compound C), and ULK1 (SBI-0206965) as well as TRPV1, CaMKKβ, and AMPK siRNA transfection. In addition, an mTOR inhibitor (rapamycin) had no significant effect on NM-stimulated autophagy or cell death of keratinocytes. Finally, the results of the in vivo experiment in NM-treated skin tissues were consistent with the findings of the in vitro experiment. In conclusion, NM-caused dermal toxicity by overactivating autophagy partially through the activation of TRPV1-Ca
-CaMKKβ-AMPK-ULK1 signaling pathway. These results suggest that blocking TRPV1-dependent autophagy could be a potential treatment strategy for NM-caused cutaneous injury.
MiR-198 has been considered as an inhibitor of cell proliferation, invasion, migration and a promoter of apoptosis in most cancer cells, while its effect on non-cancer cells is poorly understood.
The ...effect of miR-198 transfection on HaCaT cell proliferation was firstly detected using Cell Count Kit-8 and the cell cycle progression was analyzed by flow cytometry. Using bioinformatics analyses and luciferase assay, a new target of miR-198 was searched and identified. Then, the effect of the new target gene of miR-198 on cell proliferation and cell cycle was also detected.
Here we showed that miR-198 directly bound to the 3'-UTR of CCND2 mRNA, which was a key regulator in cell cycle progression. Overexpressed miR-198 repressed CCND2 expression at mRNA and protein levels and subsequently led to cell proliferation inhibition and cell cycle arrest in the G1 phase. Transfection ofSiCCND2 in HaCaT cells showed similar inhibitory effects on cell proliferation and cell cycle progression.
In conclusion, we have identified that miR-198 inhibited HaCaT cell proliferation by directly targeting CCND2.
SM (Sulfur mustard) is an oily, hydrophobic, and lipophilic chemical agent that damages cells with intricate patterns. CEES (2-chloroethyl ethyl sulfide soluble) is a standard SM analog commonly ...employed in the toxicity mechanism study. To obtain ideal results in vitro, researchers should disperse CEES well in the medium, avoiding the presence of undissolved droplets. However, such a purpose is not easy to reach under the conventional solution preparation, and the information about droplet formation and function is little available. Here, we showed that phospholipid and triglyceride, two essential components of serum lipids, could prevent CEES from dissolving in water after vortex, which kept partial CEES as small droplets. By detecting CEES level, we proved that residual droplets slowed CEES hydrolysis and conversion. Under the microscope, CEES droplets were observed to degrade and diffuse with time to induce the necrosis and mitochondrial membrane potential decline from nearby cells. In conclusion, the damage pattern of CEES droplets is quite different from that of dissolved CEES, and a low level of phospholipid and triglyceride is beneficial for preventing droplets formation in preparing CEES solution.
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