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The marine natural product fucoxanthin has been reported previously to produce anti-Alzheimer's disease (AD) neuroprotective effects in vitro and in vivo. Fucoxanthin was also demonstrated to be safe in preclinical and small population clinical studies, but the low bioavailability of fucoxanthin in the central nervous system (CNS) has limited its clinical applications. To overcome this, poly lactic-co-glycolic acid-block-polyethylene glycol loaded fucoxanthin (PLGA-PEG-Fuc) nanoparticles with diameter at around 200 nm and negative charge were synthesized and suggested to penetrate into the CNS. Loaded fucoxanthin could be liberated from PLGA-PEG nanoparticles by sustained released in the physiological environment. PLGA-PEG-Fuc nanoparticles were shown to significantly inhibit the formation of Aβ fibrils and oligomers. Moreover, these nanoparticles were taken up by both neurons and microglia, leading to the reduction of Aβ oligomers-induced neurotoxicity in vitro. Most importantly, intravenous injection of PLGA-PEG-Fuc nanoparticles prevented cognitive impairments in Aβ oligomers-induced AD mice with greater efficacy than free fucoxanthin, possibly via acting on Nrf2 and NF-κB signaling pathways. These results altogether suggest that PLGA-PEG nanoparticles can enhance the bioavailability of fucoxanthin and potentiate its efficacy for the treatment of AD, thus potentially enabling its future use for AD therapy.

Lung adenocarcinoma (LUAD) is regarded as the most common type of lung cancer. The molecular targeted therapies for LUAD have being extensively studied. Ribonuclease H2 subunit A (RNASEH2A) is a nucleotide degrading enzyme gene that exerts great influence on cell proliferation, DNA replication and genomic stability. According to bioinformatics analysis, RNASEH2A expression in LUAD tissues is predicted to be upregulated and high expression of RNASEH2A might be related to lower survival rate in LUAD patients. In the present study, we investigated functions of RNASEH2A in LUAD. The mRNA RNASEH2A showed high expression in LUAD cells, and its knockdown inhibited proliferation and induced apoptosis in LUAD cells. RNASEH2A was found to be a target gene of microRNA miR-3529-5p after their expression levels and interaction being examined. Long noncoding RNA LINC01287 upregulated RNASEH2A expression in LUAD cells by combining with miR-3529-5p in a competitive way. Rescue assays revealed that the overexpression of RNASEH2A reversed the suppression of cell proliferation and the promotion of cell apoptosis induced by miR-3529-5p overexpression or LINC01287 knockdown. Finally, forkhead box A1 (FOXA1) interacted with RNASEH2A promoter and LINC01287 promoter to upregulate the expression levels of RNASEH2A and LINC01287 in LUAD cells. Overall, FOXA1-induced LINC01287 serves as a competing endogenous RNA to promote proliferation and inhibit apoptosis of LUAD cells via upregulation of RNASEH2A expression at the posttranscriptional level by competitively combining with miR-3529-5p.

Drought is a limiting factor for wheat production. Nitric oxide (NO) and hydrogen peroxide (H2O2) are key signalling molecules produced in response to drought stress. Drought priming is a promising strategy for enhancing drought tolerance. Here, the roles of NO and H2O2 in drought priming were investigated. The results showed that the scavengers of NO or H2O2 reduced the effects of priming‐induced tolerance to drought stress during seedling and grain filling stages. Drought priming induced the production of H2O2 and NO, suggesting that H2O2 and NO were involved in priming‐induced drought tolerance and that the synthesis of H2O2 could be related to respiratory burst oxidase homologues (RBOH). Further, nitrate reductase (NR) activity was not the unique source for NO production. The elevated production of NO in the primed plants was blocked by scavengers of both H2O2 and NO, whereas the H2O2 concentration was not affected by a scavenger of NO. Osmolyte accumulation induced by drought priming was partly inhibited by the removal of NO, but was higher than in non‐primed plants. NO worked downstream of H2O2‐mediated the accumulation of proline and glycine‐betaine in primed plants under drought stress during grain filling. The results increase our understanding of the roles of H2O2 and NO in priming‐induced drought tolerance in wheat.

Arylcyclohexylamines is an ever-growing class of new psychoactive substances, including an increasing number of ketamine analogs. N-Ethylnorketamine (NENK) is a new synthetic ketamine analog that has emerged as an abused drug, but little is known about the pharmacological profile of NENK. In this study, we investigated the anesthetic and analgesic activity, abuse liability of NENK compared with ketamine. The ED

BackgroundCurcumin has multifunctional pharmacological properties, including anti-oxidant, anti-inflammatory, and anti-diabetic properties. We investigated whether curcumin can improve pathological changes associated with Alzheimer's disease, including amyloid β (Aβ), protein kinase B (PKB, also termed Akt), and glycogen synthase kinase 3β (GSK3β) levels and expression. MethodsAlzheimer’s transgenic APPSWE/PS1ΔE9 mice and wild type mice were treated with curcumin by intragastric administration for 2 weeks at 2 and 5 months of age. Aβ plaques and contents in the brain and retina were measured by immunohistochemistry and enzyme-linked immune sorbent assay, respectively, while the expression of Akt and GSK3β was tested by RNA isolation and quantitative real-time poly merase chain reaction. Bloods of patients with AD and age-matched health controls were used to determine the contents of Aβ, Akt and GSK3β. ResultsCurcumin treatment decreased Aβ accumulation in the early stages of AD at 5 months (p < 0.001). It also improved AD-associated pathological changes, including upregulation of Akt (p < 0.01) and downregulation of GSK3β (p < 0.01). In addition to AD-associated changes, the proinflammatory cytokine IL-1β was significantly decreased by curcumin treatment (p < 0.05). ConclusionsCurcumin can suppress Aβ accumulation during the early stages of AD, upregulate the expression of Akt, downregulate the expression of GSK3β, and inhibit the proinflammatory cytokine IL-1β. Curcumin can be used to improve pathological features of AD in the early stages of disease

Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a β-carboline alkaloid isolated from marine sponge Fascaplysinopsis bergquist in 1988. Previous studies have shown that fascaplysin might act on acetylcholinesterase and β-amyloid (Aβ) to produce anti-AD properties. In this study, a series of fascaplysin derivatives were synthesized. The cholinesterase inhibition activities, the neuronal protective effects, and the toxicities of these compounds were evaluated in vitro. Compounds 2a and 2b, the two most powerful compounds in vitro, were further selected to evaluate their cognitive-enhancing effects in animals. Both 2a and 2b could ameliorate cognitive dysfunction induced by scopolamine or Aβ oligomers without affecting locomotor functions in mice. We also found that 2a and 2b could prevent cholinergic dysfunctions, decrease pro-inflammatory cytokine expression, and inhibit Aβ-induced tau hyperphosphorylation in vivo. Most importantly, pharmacodynamics studies suggested that 2b could penetrate the blood-brain barrier and be retained in the central nervous system. All these results suggested that fascaplysin derivatives are potent multitarget agents against AD and might be clinical useful for AD treatment.

The dynamic characteristics of the computerized numerical control (CNC) machine tool directly affect its machining quality, and it is necessary to carry out the working mode analysis of the CNC machine tool. The traditional manual analysis and identification process is complicated and inefficient. In the industrial environment of big data, how to use the working modal analysis method to quickly and accurately obtain the dynamic characteristic parameters of the machine tool processing from these data has become the research difficulty at the current stage. This paper proposes an optimized particle swarm optimization algorithm to solve this problem. Based on the working modal analysis theory, the semi-self-power spectrum of the output signal can replace the frequency response function for modal parameter identification. The optimized semi-self-power spectrum signal is used as the objective function of the algorithm, and the ability of the algorithm to preprocess the data is optimized, so that the improved algorithm can automatically analyze the structural mode of the machine tool during processing. Comparing the experimental results, it is found that the natural frequency identification error of the cantilever beam is less than 1%, and the natural frequency identification error of the CNC milling machine is not more than 7%. The results show that the particle swarm optimization algorithm based on modal analysis theory can be applied to the automatic analysis of modal parameters under machine tool operating conditions, and it is efficient and accurate.

LncRNA CASC11 is a recently identified oncogenic lncRNA in colorectal cancer. This study aimed to investigate the role of lncRNA CASC11 in small cell lung cancer (SCLC). In the present study, expression levels of CASC11 and TGF-β1 were found to be positively and significantly correlated with the percentage of CDD133+ cells of SCLC cell lines. Plasma CASC11 and TGF-β1 were upregulated and positively correlated in SCLC patients, but not in healthy controls. Upregulation of plasma CASC11 and TGF-β1 predicted poor survival of SCLC patients. Overexpression of CASC11 and TGF-β1 also resulted in the increased percentage of CDD133+ cells of SCLC cell lines, while TGF-β inhibitor attenuated the effects of CASC11 overexpression. CASC11 overexpression mediated the upregulation of TGF-β1 in SCLC cells, while treatment with exogenous TGF-β1 showed no significant effect on CASC11. Therefore, lncRNA CASC11 promotes TGF-β1, increases cancer cell stemness and predicts postoperative survival in SCLC.

Fucoxanthin, one of the most abundant carotenoids from edible brown seaweeds, for years has been used as a bioactive dietary supplement and functional food ingredient. Recently, fucoxanthin was reported to penetrate the blood-brain barrier, and was superior to other carotenoids to exert anti-neurodegenerative disorder effects via acting on multiple targets, including amyloid protein aggregation, oxidative stress, neuroinflammation, neuronal loss, neurotransmission dysregulation and gut microbiota disorder. However, the concentration of fucoxanthin required for in vivo neuroprotective effects is somewhat high, and the poor bioavailability of this molecule might prevent its clinical use. As such, new strategies have been introduced to overcome these obstacles, and may help to develop fucoxanthin as a novel lead for neurodegenerative disorders. Moreover, it has been shown that some metabolites of fucoxanthin may produce potent in vivo neuroprotective effects. Altogether, these studies suggest the possibility for future development of fucoxanthin as a one-compound-multiple-target or pro-drug type pharmaceutical or nutraceutical treatment for neurodegenerative disorders.Trial registration: ClinicalTrials.gov identifier: NCT03625284.Trial registration: ClinicalTrials.gov identifier: NCT02875392.Trial registration: ClinicalTrials.gov identifier: NCT03613740.Trial registration: ClinicalTrials.gov identifier: NCT04761406.

Lung adenocarcinoma (LUAD) is regarded as the most common type of lung cancer. The molecular targeted therapies for LUAD have being extensively studied. Ribonuclease H2 subunit A (RNASEH2A) is a nucleotide degrading enzyme gene that exerts great influence on cell proliferation, DNA replication and genomic stability. According to bioinformatics analysis, RNASEH2A expression in LUAD tissues is predicted to be upregulated and high expression of RNASEH2A might be related to lower survival rate in LUAD patients. In the present study, we investigated functions of RNASEH2A in LUAD. The mRNA RNASEH2A showed high expression in LUAD cells, and its knockdown inhibited proliferation and induced apoptosis in LUAD cells. RNASEH2A was found to be a target gene of microRNA miR-3529-5p after their expression levels and interaction being examined. Long noncoding RNA LINC01287 upregulated RNASEH2A expression in LUAD cells by combining with miR-3529-5p in a competitive way. Rescue assays revealed that the overexpression of RNASEH2A reversed the suppression of cell proliferation and the promotion of cell apoptosis induced by miR-3529-5p overexpression or LINC01287 knockdown. Finally, forkhead box A1 (FOXA1) interacted with RNASEH2A promoter and LINC01287 promoter to upregulate the expression levels of RNASEH2A and LINC01287 in LUAD cells. Overall, FOXA1-induced LINC01287 serves as a competing endogenous RNA to promote proliferation and inhibit apoptosis of LUAD cells via upregulation of RNASEH2A expression at the posttranscriptional level by competitively combining with miR-3529-5p.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an β-amyloid (Aβ) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Aβ1-42 aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Aβ1-42 pentamers. Moreover, 13a effectively attenuated Aβ1-42 oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.

Additional file 1. Original western blotting protein bands.

BackgroundOfloxacin is an important drug with anti-bacterial effects, and (–)-ofloxacin has been shown to have better anti-bacterial activity than racemic ofloxacin. But chiral resolution of compounds is a major challenge worldwide. Many methods do not show high specificity to target molecules, causing errors in the separation of these pharmaceutical molecules, thus affecting the purity of drugs.MethodThe paper mainly research on a method for quick resolution of ofloxacin using chiral magnetic surface molecular imprinting polymers (chiral MMIP). Fe3O4 magnetic nanoparticles coated with silica is acted as the substrate. Chiral reagent is N-octyl-D-glucosamine as monomer, with ofloxacin as the template molecules to prepare magnetic surface molecularly imprinted polymer. The chiral polymer can be combined with (+)-ofloxacin, eventually (-)-ofloxacin was isolated. ResultsFinally by using extermal magnetic field and transmission electron microscopy (TEM), the character of magnetic surface molecularly imprinted polymer is tested, and The product was tested by ultraviolet spectrum and optical rotation tests and was confirmed to be (-)-ofloxacin. ConclusionA simple, rapid, and cost-effective method for separating chiral compounds was established.

To investigate the effect of lncRNA LCTS5 in the non-small cell lung cancer (NSCLC).LncRNA profiling was used to identify the novel lncRNA LCTS5. Viability and migration assays were implemented to evaluate the in vitro effect of LCTS5. Transplantation study was designed to investigate the in vivo role. Short hairpin RNA (shRNA) and lentiviral vector were used to alter LCTS5 expression.We identified a novel lncRNA named LCTS5 whose abundance is dramatically decreased in NSCLC. Overexpressing LCTS5 effectively inhibits viability and migration. Meanwhile, LCTS5 overexpression retards xenograft tumor growth and proliferation. LCTS5 interacts with INO80 to reduce INO80 occupancy at enhancer regions of multiple lung cancer related genes without affecting INO80 decay.The newly identified lncRNA LCTS5 impairs NSCLC progression and provides a compelling target for therapeutic intervention during NSCLC treatments.

Non-small cell lung carcinoma (NSCLC) accounts for 85% of all lung cancers and the five-year survival rate is ~1% in the late stage. Circular RNAs (circRNAs) were reported to be involved in the progression of diverse human cancers. However, the role of circ-ACACA in NSCLC progression remains elusive. Quantitative polymerase chain reaction was conducted to detect the expression levels of circ-ACACA and microRNA (miR)-1183 in NSCLC tissues and cells. A Cell Counting Kit-8 assay and transwell assay were employed to check proliferation and migration, respectively. Metabolic alternations in NSCLC cells were monitored by the Seahorse XFe96 analyzer. The protein levels of cellular myelocytomatosis, matrix metallopeptidase 9, glucose transporter 1, phosphatase and tensin homolog, phosphoinositide 3-kinases (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (PKB) and p-PKB in samples were measured by western blotting. The interaction between circ-ACACA and miR-1183 was predicted by circular RNA Interactome, which was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft tumor model was established to investigate the biological roles of circ-ACACA in vivo. The level of circ-ACACA was markedly upregulated in NSCLC tissues and cells, which was contrary to the expres-sion of miR-1183. Knockdown of circ-ACACA inhibited proliferation and migration of NSCLC cells and also reduced the glycolysis rate. In addition, miR-1183 was a target of circ-ACACA and its downregulation reversed circ-ACACA silencing-mediated inhibitory impact on NSCLC progression. Further studies indicated that circ-ACACA regulated the PI3K/PKB pathway through interacting with miR-1183 and downregulation of circ-ACACA suppressed tumor growth. Knockdown of circ-ACACA impeded NSCLC progression by sponging miR-1183 and inactivating the PI3K/PKB signaling pathway.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a β-carboline alkaloid isolated from marine sponge

The main pathological features of ischemic stroke include neuronal damage and blood–brain barrier (BBB) dysfunction. Previous studies have shown that Evans Blue, a dye used to probe BBB integrity, could enter the brain only during the pathological status of ischemic stroke, indicating the potential pathologically activated therapeutic use of this chemical to treat ischemic stroke. In this study, we have reported that Evans Blue could produce in vitro neuroprotective effects against iodoacetic acid (IAA)-induced hypoxia neuronal death in HT22 cells. We further found that P2X purinoreceptor 4 (P2X4R), a subtype of ATP-gated cation channel, was expressed in HT22 cells. Evans Blue could prevent IAA-induced increase of P2X4R mRNA and protein expression. Interestingly, shRNA of P2X4R could protect against IAA-induced activation of p38, and SB203580, a specific inhibitor of p38, could reverse IAA-induced neurotoxicity, indicating that p38 is a downstream signaling molecule of P2X4R. Molecular docking analysis further demonstrated the possible interaction between Evans Blue and the ATP binding site of P2X4R. Most importantly, pre-treatment of Evans Blue could largely reduce neurological and behavioral abnormity, and decrease brain infarct volume in middle cerebral artery occlusion/reperfusion (MCAO) rats. All these results strongly suggested that Evans Blue could exert neuroprotective effects via inhibiting the P2X4R/p38 pathway, possibly by acting on the ATP binding site of P2X4R, indicating that Evans Blue might be further developed as a pathologically activated therapeutic drug against ischemic stroke.

The aim of the present study was to analyze the stem cell marker, Nanog gene, for the diagnosis and prognosis of lung cancer cases, and to study its application in the diagnosis of lung cancer. In total, 100 patients diagnosed with lung cancer between April, 2013 and May, 2015 were included in the present study. The patients were randomly divided into group A (lung cancer) and group B (squamous cell lung carcinoma). RT-PCR was used to detect the cancer and adjacent tissues, and Nanog gene expression was detected in groups A and B in cells. The results showed that, analysis of Nanog gene expression in the two groups of patients varied to different degrees. There was no significant difference between the two groups with regard to age, gender, disease stage and lymph node metastasis. Nanog gene expression in patients with carcinoma were significantly higher than that in the adjacent tissues (p

Aims To investigate the effect of lncRNA LCTS5 in the non-small cell lung cancer (NSCLC). Materials and methods LncRNA profiling was used to identify the novel lncRNA LCTS5. Viability and migration assays were implemented to evaluate the in vitro effect of LCTS5. Transplantation study was designed to investigate the in vivo role. Short hairpin RNA (shRNA) and lentiviral vector were used to alter LCTS5 expression. Key findings We identified a novel lncRNA named LCTS5 whose abundance is dramatically decreased in NSCLC. Overexpressing LCTS5 effectively inhibits viability and migration. Meanwhile, LCTS5 overexpression retards xenograft tumor growth and proliferation. LCTS5 interacts with INO80 to reduce INO80 occupancy at enhancer regions of multiple lung cancer related genes without affecting INO80 decay. Significance The newly identified lncRNA LCTS5 impairs NSCLC progression and provides a compelling target for therapeutic intervention during NSCLC treatments.

Pathological β-amyloid (Aβ)-induced microglial activation could cause chronic neuroinflammation in the brain of Alzheimer's disease (AD) patients, and has been considered as one of the main pathological events of this disease. Chicago sky blue 6B (CSB6B), a pigment used in biochemical staining, has been reported to produce analgesic effects in neuroinflammatory-associated pain models. We have previously found that CSB6B could directly inhibit Aβ aggregation and prevent Aβ toxicity in neurons. However, it remains unclear whether this compound could prevent Aβ-induced neuroinflammation and impairments of learning and memory in the AD models. In this study, CSB6B was found to effectively inhibit the production of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, without affecting cell viability in BV2 microglia cells stimulated by Aβ oligomer and lipopolysaccharide. Moreover, CSB6B significantly reduced mRNA expression of inducible nitric oxide synthase and increased mRNA expression of arginase-1, suggesting that CSB6B might promote the polarization of BV2 cells into M2 phenotype. In Aβ oligomer-treated mice, hippocampal injection of CSB6B prevented cognitive impairments, and attenuated pro-inflammatory cytokines production. In addition, CSB6B inhibited nuclear transcription factor-κB (NF-κB), and restrainedthe activation of NOD-like receptor pyrin domain containing-3 (NLRP3) both in vitro and in vivo. According to our results, CSB6B may counteract Aβ-induced cognitive impairments and neuroinflammation by inhibiting NF-κB and NLRP3. Combined with previous studies, we anticipated that CSB6B may further develop into a potential anti-AD drug with multiple functions on neurons and microglia cells, concurrently.

Background Pancreatic cancer is a devastating invasive disease. Understanding the molecular mechanism of metastasis of this cancer is basis for its treatment and prevention. Methods Pancreatic cancer tissues and normal adjacent tissues were collected from patients tour hospital. Western blotting and a sphere growth and invasion assay were performed to conduct analysis. Pancreatic ductal adenocarcinoma cell Line PANC-1 were cultured. To test the level of Raf-1 kinase inhibitor protein (RKIP), immunofluorescence analyses were performed. Results In this study, we showed that expression of RKIP was downregulated in pancreatic cancer. RKIP can inhibit epithelial to mesenchymal transition (EMT) in PANC-1 cells. MicroRNA-181a (miR-181a) has a high expression in pancreatic cancer and can induce EMT phenotype by directly degrading RKIP in pancreatic cancer PANC-1 cells. Conclusions We concluded that miR-181a induces EMT phenotype through its regulation of RKIP in pancreatic cancer. MicroRNA-18a may be a novel target in the treatment of pancreatic cancer in future.

Two new γ-lactones, aspergilactones A (1) and B (2), were discovered along with two known compounds, annularin A (3) and pericoterpenoid A (4), from a culture of the sponge-associated fungus Aspergillus sp. LS45. The planar structures of 1–4 were characterized using comprehensive spectroscopic methods and comparison with literature data. The absolute configurations of 1 and 2 were determined by comparison of electronic circular dichroism (ECD) spectroscopic and optical rotation data with those of known analogues as well as calculated ECD analysis. Compounds 1–4 were tested in a variety of bioassays, and both 1 and 4 exhibited significant inhibition against the lateral root growth of Arabidopsis thaliana Columbia-0 at a concentration of 100 μM. In addition, the in vitro cytotoxic activities of 1–4 against six human cancer cell lines CCRF-CEM, K562, BGC823, AGS, HCT-116 and MDA-MB-231 were evaluated. Compound 4 showed moderate inhibitory effects on CCRF-CEM and K562 cancer cell lines with IC50 values of 13.8 ± 1.6 and 12.9 ± 2.5 μM, respectively. However, compounds 1–4 did not show any notable AChE inhibitory activity in vitro.

25C-NBOMe is a designer substituted phenethylamine and a high-potency psychedelic that acts on the 5-HT2A receptor. Although 25C-NBOMe overdoses have been related to several deaths in the USA and Europe, very limited data exists on the in vitro neurotoxicity of 25C-NBOMe. In this study, we found that 25C-NBOMe potently reduced cell viability of SH-SY5Y, PC12, and SN4741 cells, with IC50 values of 89, 78, and 62 μM, respectively. Methamphetamine decreased the cell viability of these cells with IC50 values at millimolar range in the same tests, indicating that 25C-NBOMe is > 50 times more potent than methamphetamine in its ability to reduce viability of SH-SY5Y cells. The neurotoxicity of 25C-NBOMe on SH-SY5Y cells was further confirmed by using fluorescein diacetate/propidium iodide double staining. 25C-NBOMe elevated the expression of phosphorylated extracellular signal-regulated kinase (pERK), but decreased the expression of phosphorylated Akt and phosphorylated Ser9- glycogen synthase kinase 3β (GSK3β) in time- and concentration-dependent manners. Interestingly, either specific GSK3β inhibitors or specific mitogen-activated protein kinase kinase (MEK) inhibitors significantly prevented 25C-NBOMe-induced neurotoxicity in SH-SY5Y cells. These results suggest that 25C-NBOMe unexpectedly produced more potent neurotoxicity than methamphetamine and that the inhibition of the Akt pathway and activation of the ERK cascade might be involved in 25C-NBOMe-induced neurotoxicity. Most importantly, these findings further inform the toxicity of 25C-NBOMe abuse to the central nervous system for public health.

The metastasis-associated gene 1 (MTA1) has previously been recognized as an oncogene in many tumors, and aberrant MTA1 expression has been related to invasion and migration; however, its role and underlying molecular mechanism in oral squamous carcinoma (OSCC) remain largely unexplored. In this work, we determined the expression of MTA1 in OSCC tissues and cell lines. The effect of MTA1 on metastasis and the role of MTA1 in the epithelial-to-mesenchymal transition (EMT) of OSCC cells were evaluated by assays both in vitro and in vivo. We also identified the key Hedgehog signaling pathway-related protein involved in the MTA1-induced EMT. We found that MTA1 expression was upregulated and positively related to the metastasis in OSCC tissues and cell lines. MTA1 overexpression promoted OSCC invasion, migration, and induced EMT, while its silencing had the opposite effect both in vitro and in vivo. Additionally, our data further revealed the relevant molecular mechanism, Hedgehog(Hh) signaling pathway contributed to the effect of MTA1 on the aggressive phenotypes of OSCC cells.These findings indicate that MTA1 enhances OSCC cells invasion and migration by inducing EMT via the Hedgehog signaling pathway, which suggests MTA1 may be an effective anti-OSCC therapeutic target.

The vibration of machine tool plays an important role in surface generation. However, the vibration characteristics is different for different machine tool structures and different machining path. This paper proposed a new method of structural sensitivity analysis to identify trajectory dependent structural vibration and its effect on surface generation in milling. The experimental and theoretical results verify that (i) Multimode low-frequency vibration of the sensitive structures (MLFVSS) directly determines the surface topography in milling; (ii) The sensitivity is different for different structures or the same structure at different modes; (iii) Structural vibration characteristics is related to the machining path, resulting in different influence of the structural vibration on surface generation at different position of the machining path. Finally, a surface topography prediction model was established based on the experimental results. This study is helpful to the optimization of machine tool structures and the selection of machining parameters.

Non-small cell lung carcinoma (NSCLC) metastasis is responsible for most of cancer-related mortality. The tumor associated macrophages (TAMs) are known to be crucial cells in lung cancer and are usually divided into two antagonistic types, M1 and M2. Puerarin has a wide spectrum of pharmacological properties. The present study explores puerarin on macrophage polarization and metastasis of NSCLC. The results demonstrated that puerarin inhibited tumor growth and tumor volumes in NSCLC xenograft model, increased M1 markers [CD197+, inducible nitric oxide synthase (iNOS)+, CD40+)] and reduced M2 markers (CD206+, Arg-1+ and CD163+). Besides, puerarin elevated the level of pro-inflammatory cytokine interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-12, decreased the expression of pro-tumor cytokines IL-10, IL-4 and transforming growth factor (TGF)-β. To explore whether puerarin directly acts on macrophages, we purified macrophages from NSCLC model, the results showed that puerarin inhibited macrophages polarized to M2 phenotype and did not require the auxiliary of other cells. In addition, puerarin suppressed the invasion and migration of NSCLC macrophages, restrained the expression of angiogenesis factors. Puerarin also inhibited the activation of mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) 1/2 pathway through inhibition of ERK nucleus translocation. Finally, IL-4 induced M2 macrophage polarization and metastasis were partially offset by puerarin through inactivating the MEK/ERK 1/2 pathway. Taken together, this study validated that puerarin is able to skew macrophage populations back to M1 subsets to stimulate antitumor effects and suggests puerarin is a negative metastatic regulator of NSCLC.

The aim of the present study was to analyze the stem cell marker, Nanog gene, for the diagnosis and prognosis of lung cancer cases, and to study its application in the diagnosis of lung cancer. In total, 100 patients diagnosed with lung cancer between April, 2013 and May, 2015 were included in the present study. The patients were randomly divided into group A (lung cancer) and group B (squamous cell lung carcinoma). RT-PCR was used to detect the cancer and adjacent tissues, and Nanog gene expression was detected in groups A and B in cells. The results showed that, analysis of Nanog gene expression in the two groups of patients varied to different degrees. There was no significant difference between the two groups with regard to age, gender, disease stage and lymph node metastasis. Nanog gene expression in patients with carcinoma were significantly higher than that in the adjacent tissues (p