Selective removal of iron from sulfuric acid leaching solution of aerospace magnetic material scraps by jarosite process.

Aerospace magnetic material scraps are abundant in cobalt and nickel. Sulfuric acid leaching process is an efficient method for extracting them. But it is a non-selective process, a significant amount of iron dissolves in the solution. This study focuses on the selective removal of iron from this solution using the jarosite process. Eh-pH diagram of K-S-Fe-H2O system was established. Based on thermodynamic analysis, H2O2 is used to oxidize Fe2+ into Fe3+, achieving efficient and selective removal of iron from the solution containing cobalt and nickel. The optimal conditions are as follows: temperature 95°C, K2SO4 dosage coefficient 1.5, seed dosage 10 g/L, time 90 min, pH 1.76, and endpoint pH controlled at approximately 3. Under these conditions, the iron removal efficiency is above 99%, while the loss ratios of cobalt and nickel are below 2%. The product is characterized by XRD and SEM-EDS. Results indicate that the product is jarosite ((K,H3O)Fe3(SO4)2(OH)6), exhibiting an ellipsoid structure with the mean particle size in the range of 0.2-5.0 µm. Temperature, pH value and seed dosage significantly affect reaction rate, particle size and crystallinity, and K2SO4 dosage mainly affects reaction rate and the morphology of jarosite. The jarosite crystallization kinetics can be described by the Avrami equation, with an Avrami index (n) of approximately 2.5 and the apparent activation energy of 42.68 kJ/mol.

Effects of Simulated Weightlessness on Metabolizing Enzymes and Pharmacokinetics of Folic Acid in SD Rats.

Folic acid (FA) affect human physiology and drug metabolism. Up to now, the effect of microgravity on the pharmacokinetics of FA remains unclear. The pharmacokinetics of FA in Sprague-Dawley (SD) rats are laying a foundation for safe medicine administration of astronauts. Proteins expression of such FA metabolic enzymes as Methyltetrahydrofolate reductase (MTHFR), Cystathionine beta synthase (CBS) and Methionine synthase (MS) in a variety of organs was analyzed with Western-Blot, and mRNA expression was detected by RT-PCR. The plasma concentration-time profile of FA in normal or tail-suspended SD rats was acquired by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after oral administration of FA. Area under curve (AUC) and Cmax of FA in SD rats decreased significantly with extending period of tail-suspension. In terms of expressed level of metabolic enzymes over four suspension terms, as well as the level of the corresponding mRNAs, the following regularities were found: an obvious sharp decline of MTHFR tissue in kidney, a time-dependent increase of CBS in liver tissue and duodenum tissues, the resemblance of MS fluctuation to that of CBS in tested tissues. A four-week simulated microgravity of SD rats exhibits an unequivocal diminish of bioavailability of FA, and simulated microgravity shows a varying effect on the expression of FA-metabolizing enzyme in a variety of tissues.

Enrichment and purification of red pigments from defective mulberry fruits using biotransformation in a liquid-liquid-solid three-phase system.

A large number of defective mulberries are discarded each year because mulberries are easy to break. The red pigments from defective mulberries are recognized as the sustainable sources of anthocyanins extracted from nature. Cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside are the main components of mulberry red pigments, accounting for 50% and 40% of the total, respectively. Cyanidin-3-O-glucoside exhibits anticancer, hypoglycemic, and liver and visceral protection properties. Cyanidin-3-O-glucoside can be prepared by enzymatically hydrolyzing the rhamnosidase bond of cyanidin-3-O-rutinoside. To obtain mulberry red pigment with a high purity of cyanidin-3-O-glucoside, immobilized α-L-rhamnosidase was added to the aqueous two-phase system to construct a liquid-liquid-solid three-phase enzyme catalytic system. After optimization, the three-phase system was composed of 27.12% (w/w) ethanol, 18.10% (w/w) ammonium sulfate, 15% (w/w) mulberry juice, 4.24% (w/w) immobilized α-L-rhamnosidase, and 35.54% (w/w) pure water. The three-phase system was employed to enrich and purify cyanidin-3-O-glucoside at pH 5 and 45 °C for 1 h. The purity of cyanidin-3-O-glucoside was increased from 40 to 82.42% with cyanidin-3-O-rutinoside conversion of 60.68%. The immobilized α-L-rhamnosidase could be reused seven times, maintaining a relative activity of over 50%. Overall, the developed system provided an efficient and simple approach for high purity mulberry red pigment production and recycling in the field of sustainable agriculture. Graphical abstract.

The novel ALK inhibitor ZX-29 induces apoptosis through inhibiting ALK and inducing ROS-mediated endoplasmic reticulum stress in Karpas299 cells.

It is a well-known fact that 60%-85% of anaplastic large cell lymphoma (ALCL) is mainly driven by the anaplastic lymphoma kinase (ALK) fusion protein. Although ALK-positive ALCL patients respond significantly to ALK inhibitors, the development of resistance is inevitable, which requires the development of new therapeutic strategies for ALK-positive ALCL. Here, we investigated the anticancer activities of N-(2((5-chloro-2-((2-methoxy-6-(4-methylpiperazin-1-yl)pyridin-3yl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide (ZX-29), a newly synthesized ALK inhibitor, against nucleophosmin-ALK-positive cell line Karpas299. We demonstrated that ZX-29 decreased Karpas299 cells growth and had better cytotoxicity than ceritinib, which was mediated through downregulating the expression of ALK and related proteins, inducing cell cycle arrest, and promoting cell apoptosis. Moreover, ZX-29-induced cell apoptosis by inducing endoplasmic reticulum stress (ERS). In addition, ZX-29 increased the generation of reactive oxygen species (ROS), and cells pretreatment with N-acetyl- l-cysteine could attenuate ZX-29-induced cell apoptosis and ERS. Taken together, ZX-29 inhibited Karpas299 cell proliferation and induced apoptosis through inhibiting ALK and its downstream protein expression and inducing ROS-mediated ERS. Therefore, our results provide evidence for a novel antitumor candidate for the further investigation.

Opsoclonus-myoclonus syndrome associated with herpes simplex virus infection: a case report.

Purpose: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease that can be associated with autoimmunity, paraneoplastic tumour, infection or unknown aetiology.Methods: We describe a 54-year-old woman who developed severe OMS, with the clinical onset occurring 2 months and 15 days after she experienced dizziness, vomiting and fever related to a herpes simplex virus infection. The patient was treated with hormones and clonazepam, and the symptoms of myoclonus and ataxia disappeared.Results: The patient was followed up for 1 year with no recurrence of symptoms.Conclusions: The case suggests that herpes simplex virus infection is a possible cause of OMS.

Inhibition of p38 MAPK regulates epileptic severity by decreasing expression levels of A1R and ENT1.

Epilepsy is a chronic nervous system disease. Excessive increase of the excitatory neurotransmitter glutamate in the body results in an imbalance of neurotransmitters and excessive excitation of neurons, leading to epileptic seizures. Long­term recurrent seizures lead to behavior and cognitive changes, and even increase the risk of death by 2­ to 3­fold relative to the general population. Adenosine A1 receptor (A1R), a member of the adenosine system, has notable anticonvulsant effects, and adenosine levels are controlled by the type 1 equilibrative nucleoside transporter (ENT1); in addition the p38 MAPK signaling pathway is involved in the regulation of ENT1, although the effect of its inhibitors on the expression levels of A1R and ENT1 is unclear. Therefore, in the present study, SB203580 was used to inhibit the p38 MAPK signaling pathway in rats, and the expression levels of A1R and ENT1 in the brain tissue of rats with acute LiCl­pilocarpine­induced status epilepticus was detected. SB203580 decreased pathological damage of hippocampal neurons, prolonged seizure latency, reduced the frequency of seizures, and decreased levels of A1R and ENT1 protein in rats.

Dynamic-related protein 1 inhibitor eases epileptic seizures and can regulate equilibrative nucleoside transporter 1 expression.

BACKGROUND: Dynamic-related protein 1 (Drp1) is a key protein involved in the regulation of mitochondrial fission, and it could affect the dynamic balance of mitochondria and appears to be protective against neuronal injury in epileptic seizures. Equilibrative nucleoside transporter 1 (ENT1) is expressed and functional in the mitochondrial membrane that equilibrates adenosine concentration across membranes. Whether Drp1 participates in the pathogenesis of epileptic seizures via regulating function of ENT1 remains unclear. METHODS: In the present study, we used pilocarpine to induce status epilepticus (SE) in rats, and we used mitochondrial division inhibitor 1 (Mdivi-1), a selective inhibitor to Drp1, to suppress mitochondrial fission in pilocarpine-induced SE model. Mdivi-1administered by intraperitoneal injection before SE induction, and the latency to firstepileptic seizure and the number of epileptic seizures was thereafter observed. The distribution of Drp1 was detected by immunofluorescence, and the expression patterns of Drp1 and ENT1 were detected by Western blot. Furthermore, the mitochondrial ultrastructure of neurons in the hippocampal CA1 region was observed by transmission electron microscopy. RESULTS: We found that Drp1 was expressed mainly in neurons and Drp1 expression was significantly upregulated in the hippocampal and temporal neocortex tissues at 6 h and 24 h after induction of SE. Mitochondrial fission inhibitor 1 attenuated epileptic seizures after induction of SE, reduced mitochondrial damage and ENT1 expression. CONCLUSIONS: These data indicate that Drp1 is upregulated in hippocampus and temporal neocortex after pilocarpine-induced SE and the inhibition of Drp1 may lead to potential therapeutic target for SE by regulating ENT1 after pilocarpine-induced SE.

ZX-29, a novel ALK inhibitor, induces apoptosis via ER stress in ALK rearrangement NSCLC cells and overcomes cell resistance caused by an ALK mutation.

Although anaplastic lymphoma kinase (ALK) inhibitors have good clinical efficacy, the inevitable development of drug resistance is the most common obstacle to their clinical application. There is an urgent need to develop more effective and selective ALK inhibitors to overcome the problem of drug resistance. Here, we screened a series of ALK inhibitors and found that ZX-29 displayed potent cytotoxic activity against ALK rearrangement non-small cell lung cancer (NSCLC) NCI-H2228 cells. Then, we investigated the antitumor effects of ZX-29. We demonstrated that ZX-29 time- and dose-dependently inhibited the viability of NCI-H2228 cells, induced cell cycle arrest in the G1 phase, and then they subsequently progressed into cell death. The type of cell death induced by ZX-29 was apoptosis through endoplasmic reticulum (ER) stress. Interestingly, ZX-29 induced protective autophagy, and inhibiting autophagy could enhance the antitumor effect of ZX-29. Furthermore, ZX-29 suppressed tumor growth in a mouse xenograft model. More importantly, ZX-29 could overcome the drug resistance caused by the ALK G1202R mutation. In conclusion, we demonstrated that ZX-29 showed excellent anti-ALK rearrangement NSCLC activity in vitro and in vivo and overcame the drug resistance caused by an ALK mutation. Therefore, ZX-29 is a promising antitumor drug targeting ALK rearrangement or ALK G1202R mutation NSCLC.

A novel ALK inhibitor ZYY inhibits Karpas299 cell growth in vitro and in a mouse xenograft model and induces protective autophagy.

In recent years, anaplastic lymphoma kinase (ALK) rearrangement-positive anaplastic large cell lymphoma (ALCL) has rising morbidity and mortality. Unfortunately, no ALK inhibitor has been approved by the FDA for single treatment of ALK rearrangement-positive ALCL. In this study, we investigated the antitumor effect of ZYY, a novel ALK inhibitor, showing a strong growth inhibitory effect on Karpas299 cells in vitro and in vivo. Specifically, ZYY significantly reduced the mRNA and protein expression of ALK and its downstream signaling proteins in Karpas299 cells. Furthermore, ZYY induced G1 phase arrest and promoted apoptosis in Karpas299 cells. Furthermore, we demonstrated that ZYY-induced apoptosis was mainly related to the mitochondria-dependent endogenous pathway. In vitro studies further showed that ZYY induced autophagy in Karpas299 cells, along with increased levels of the autophagy-related proteins, including LC3II and Beclin-1. Moreover, knockdown Beclin-1 and application of autophagy inhibitor chloroquine potentiated ZYY-induced cytotoxicity and apoptosis in vitro, indicating that cytoprotective autophagy might be triggered by ZYY in Karpas299 cells. Taken together, the novel ALK inhibitor ZYY has tremendous potential for treating human ALCL, and a combination of autophagy and ALK inhibition could effectively elicit potent antitumor effects.

Acetaldehyde Induces Neurotoxicity In Vitro via Oxidative Stress- and Ca2+ Imbalance-Mediated Endoplasmic Reticulum Stress.

Excessive drinking can damage brain tissue and cause cognitive dysfunction. Studies have found that the early stage of neurodegenerative disease is closely related to heavy drinking. Acetaldehyde (ADE) is the main toxic metabolite of alcohol. However, the exact mechanisms of ADE-induced neurotoxicity are not fully clear. In this article, we studied the cytotoxic effect of ADE in HT22 cells and primary cultured cortical neuronal cells. We found that ADE exhibited cytotoxicities against HT22 cells and primary cultured cortical neuronal cells in dose-dependent manners. Furthermore, ADE induced apoptosis of HT22 cells by upregulating the expression of caspase family proapoptotic proteins. Moreover, ADE treatment could significantly increase the intracellular Ca2+ and reactive oxygen species (ROS) levels and activate endoplasmic reticulum stress (ERS) in HT22 cells. ADE upregulated ERS-related CHOP expression dose-dependently in primary cultured cortical neuronal cells. In addition, inhibition of ROS with antioxidant N-acetyl-L-cysteine (NAC) reduced the accumulation of ROS and reversed ADE-induced increase of ERS-related protein and apoptosis-related protein levels. Mitigation of ERS with ERS inhibitor 4-PBA obviously suppressed ADE-induced apoptosis and the expression of ERS-related proteins. Therefore, ADE induces neurotoxicity of HT22 cells via oxidative stress- and Ca2+ imbalance-mediated ERS.

Silver nanoparticles induce protective autophagy via Ca2+/CaMKKß/AMPK/mTOR pathway in SH-SY5Y cells and rat brains.

Silver nanoparticles (AgNPs) are widely used for manufacturing products containing antibacterial agents, as well as food technologies such as edible films and food packaging. Routes of AgNPs exposure are principally derived by contacting with certain medical sprays, food, toothpaste, and purification products. Previously, we showed that AgNPs induce endoplasmic reticulum (ER) stress and promote apoptosis progression in SH-SY5Y cells; however, whether AgNP-induced ER stress is able to trigger autophagy in vivo and in vitro, and the role of autophagy in AgNP-induced cytotoxicity remain unclear. In the present study, we found that increased intracellular calcium (Ca2+) levels arising from AgNP-induced-ER stress resulted in activation of calmodulin-dependent protein kinase kinase ß (CaMKKß) and adenosine 5'-monophosphate-activated protein kinase (AMPK), which downregulated the level of mammalian target of rapamycin (mTOR) and upregulated Beclin-1 to activate autophagy in SH-SY5Y cells. Specifically, inhibition of autophagy by the addition of chloroquine (CQ) or silencing of Beclin-1 significantly enhanced the cytotoxicity of AgNPs, suggesting that autophagy plays a protective role in AgNP-induced cell apoptosis. Furthermore, we showed that oral administration of AgNPs for 28 continuous days induced ER stress-mediated apoptosis and autophagy in rats via activation of CaMKKß and AMPK. In summary, this study is the first to report that AgNPs induce protective autophagy via a Ca2+/CaMKKß/AMPK/mTOR pathway in vivo and in vitro. Therefore, public exposure to AgNPs should arouse concerns regarding environmental safety and human health. Highlight Silver nanoparticle-induced ER stress elicits protective autophagy via a Ca2+-dependent mechanism in SH-SY5Y cells. The Ca2+/CaMKKß/AMPK/mTOR pathway is involved in autophagy. Orally administered silver nanoparticles induce ER stress-mediated autophagy and apoptosis in rats.

Chemical Component Optimization Based on Thermodynamic Calculation of Fe-1.93Mn-0.07Ni-1.96Cr-0.35Mo Ultra-High Strength Steel.

Due to the complex composition and high proportion of alloys in traditional ultra-high-strength steel, the dilemma caused by ultra-high strength and low toughness in casting and forging forming processes requiring subsequent heat treatment can be mitigated with an efficient and economical rolling process. In this work, a thermodynamic model is proposed to calculate the change in the mechanical response due to the thermal contribution based on alloy phase diagrams. The influence of alloy content on precision laws was analyzed, and the chemical component was optimized. A verification simulation without real experiment was conducted to study the potential and limitations of the alloy content on mechanical properties. The results showed that the main equilibrium phases and the phases' chemical compounds were clarified. The influences of Ni, Mo, Cr, and W on transformation laws were elucidated in detail, and the main optimized composition was determined to be 0.23C, 1.96Si, 1.93Mn, 0.07Ni, 1.96Cr, and 0.35Mo. At a cooling rate of 10 °C/s, the content of optimized alloying element fully performed its role in steel, verifying that the chemical component system was in the optimal range. The thermodynamic models and our conclusions have the potential to be generalized for many other materials and process configurations without requiring extensive material testing.

Titanium dioxide nanoparticles induce mouse hippocampal neuron apoptosis via oxidative stress- and calcium imbalance-mediated endoplasmic reticulum stress.

The purpose of this study was to explore the potential neurotoxicity and the underlying mechanism of titanium dioxide nanoparticles (TiO2-NPs) to mouse hippocampal neuron HT22 cells. We found that TiO2-NPs had concentration-dependent and time-dependent cytotoxicities to HT22 cells by the MTT assay. Propidium iodide (PI) staining with FACScan flow cytometry proved that TiO2-NPs dose-dependently increased the apoptosis rate in HT22 cells, and the apoptotic features were observed by Hochest 33258 and AO/EB staining. The levels of calcium (Ca2+) and reactive oxygen species (ROS) were significantly increased in TiO2-NPs-treated cells. Further studies by western blot and real-time QPCR proved that the protein and mRNA levels of GRP78, IRE-1α, ATF6, CHOP and caspase-12 were up-regulated after TiO2-NPs treatment, which indicates that TiO2-NPs-induced cytotoxicity is related to endoplasmic reticulum stress (ERS). Apoptosis-related protein cleaved caspase-3 and pro-apoptotic protein Bax expression levels were up-regulated, and the anti-apoptotic protein Bcl-2 expression level was down-regulated in TiO2-NPs-treated cells. The antioxidant N-acetyl-L-cysteine (NAC) can significantly reduce TiO2-NPs-induced ERS characterized by the down-regulation of GRP78 and cleaved caspase-12 levels, which indicates that oxidative stress is participated in TiO2-NPs-induced ERS. Our study suggests that TiO2-NPs-induced apoptosis in HT22 cells is through oxidative stress- and calcium imbalance-mediated ERS.

Alcohol aggravates ketamine-induced behavioral, morphological and neurochemical alterations in adolescent rats: The involvement of CREB-related pathways.

Currently, an increasing proportion of adolescent ketamine users simultaneously consume alcohol. However, the potential behavioural and neurological alterations induced by such a drug combination and the underlying mechanisms have not been systematically examined. Therefore, in the present study, the behavioural and morphological changes and the underlying mechanisms were studied in adolescent rats after repeated alcohol and/or ketamine treatment. This study provided the first evidence that co-administration of alcohol (2 and 4 g/kg, i.g.) in adolescent rats significantly potentiated the neurotoxic properties of repeated ketamine (30 mg/kg, i.p.) treatments over 14 days, manifesting as increased locomotor activity, stereotypic behaviour, ataxia and morphological changes. This potentiation was associated with the enhancement by alcohol of ketamine-induced glutamate (Glu) and dopamine (DA) release in the cortex and hippocampus. Further mechanistic study demonstrated that alcohol potentiated ketamine-induced neurotoxicity through down-regulation of Akt (a serine/threonine kinase or protein kinase, PKB), protein kinase A (PKA), calmodulin-dependent kinase IV (CaMK-IV)-mediated cyclic AMP-responsive element binding protein (CREB) pathways and induction of neuronal apoptosis in the cortex and hippocampus of the adolescent rats. As this study provides strong evidence that repeated alcohol and ketamine co-exposure may cause serious neurotoxicity, attention needs to be drawn to the potential risk of this consumption behaviour, especially for adolescents.

CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib.

The c-ros oncogene 1 (ROS1) is a receptor tyrosine kinase, which has been identified as an oncogene driver of non-small-cell lung cancer (NSCLC). Although crizotinib has a prominent effect on ROS1, resistance is inevitable. Development of the acquired ROS1 G2032R mutation has been reported as a resistant mechanism to ROS1 inhibitors in ROS1-rearranged (ROS1+) NSCLC patients. To explore the mechanism of drug resistance, we constructed the crizotinib resistance cell line, A549-CD74-ROS1 G2032R mutation cells, by the methods of fusion polymerase chain reaction (PCR), plasmid construction and cell transfection in vitro. The results showed that the expression of CD74-ROS1 or CD74-ROS1 G2032R mutation in A549 cells induced epithelial-mesenchymal transition (EMT), dramatically enhanced the ability of invasion and migration, and increased expression of matrix metalloproteinase (MMP)-9 and Twist1 transcription factor. Moreover, we found that inhibition of Twist1 could reverse EMT induced by CD74-ROS1 G2032R mutation. Combination of Twist1 siRNA and crizotinib significantly reduced cell vitality, inhibited cell invasion and migration, and promoted apoptosis in A549-CD74-ROS1 G2032R mutation cells. Taken together, these results suggested that CD74-ROS1 G2032R mutation mediated EMT phenotype by increasing the expression of Twist1, resulting in drug resistance. Combination of Twist1 silence and ROS1 inhibitor may provide a potent strategy to treat the ROS1+ NSCLC patients with crizotinib resistance.

Silver nanoparticles induce SH-SY5Y cell apoptosis via endoplasmic reticulum- and mitochondrial pathways that lengthen endoplasmic reticulum-mitochondria contact sites and alter inositol-3-phosphate receptor function.

Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response. Prolonged exposure of cells to AgNPs damaged calcium (Ca2+) homeostasis, increased the length of contact sites between the ER and mitochondria, altered IP3R function by the increased levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the ER and enhanced mitochondrial Ca2+ uptake. Finally, Ca2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death. Our results suggest that caution should be exercised in the use of AgNPs in humans.

Three dimensional hierarchical heterostructures of g-C3N4 nanosheets/TiO2 nanofibers: Controllable growth via gas-solid reaction and enhanced photocatalytic activity under visible light.

Graphitic C3N4 nanosheets were uniformly grown on electrospun TiO2 nanofibers with three-dimensional nanofibrous networks via a facial gas-solid reaction. The mass loading of g-C3N4 nanosheets could be easily controlled by adjusting the mass ratios of gaseous precursors (urea) to TiO2 NFs. The three-dimensional hierarchical heterostructures of g-C3N4 nanosheets/TiO2 nanofibers could be obtained with excellent distribution and high specific surface area of 121.5m2g-1, when the mass loading of g-C3N4 was 59.8wt.%. Under visible light irradiation, the degradation rate constant (rhodamine B) and the H2 evolution rate of the heterostructures were about 4.6 and 1.6 times of pure g-C3N4, while 23 and 167.8 times of TiO2 nanofibers, respectively. Their enhanced performance could be attributed to the effective charge separation and electron transfer process. Our work provides an attractive strategy to construct various three-dimensional hierarchical heterostructures of g-C3N4 nanosheets for environmental and energy applications.

Effects of yak-activated protein on hematopoiesis and related cytokines in radiation-induced injury in mice.

The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation. Yak-activated protein was administered orally to mice in the treatment groups and an equal volume of saline was administered orally to mice in the normal control and radiation model groups for 14 days. The positive control group received amifostine (150 mg/kg) via intraperitoneal injection. With the exception of the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body once. Changes in the peripheral hemogram, thymus and spleen indices, DNA content in the bone marrow, interleukin (IL)-2 and IL-6 levels, and the expression levels of B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) following irradiation were assessed. The low dose of yak-activated protein significantly increased Spleen indices in mice 14 days after irradiation and the high and middle dose of yak-activated protein significantly increased Thymus indices in mice 14 days after irradiation (P<0.05) compared with the control group. In addition, hemogram results increased gradually in the low-yak-activated protein dose group and were significantly higher 7 days after irradiation compared with the radiation model group (P<0.05). The DNA content in the bone marrow was markedly increased in the yak-activated protein groups, and increased significantly in the low dose group at 7 days post-irradiation compared with the radiation model group (P<0.05). The IL-2 content was significantly increased in the yak-activated protein groups (P<0.05). Furthermore, Bcl-2 expression was increased and Bax expression was decreased (P<0.05). These results suggest that yak-activated protein exerts protective effects against radiation-induced injury in mice. The optimal effects of yak-activated protein were observed in the medium dose group 14 days after irradiation.

Alcohol amplifies ketamine-induced apoptosis in primary cultured cortical neurons and PC12 cells through down-regulating CREB-related signaling pathways.

Recreational use of ketamine (KET) has been increasing worldwide. Previous studies have demonstrated that KET induced neurotoxicity; however, few studies have examined how alcohol (ALC) affects KET-induced neurotoxicity. In light of the fact that some KET abusers combine KET with ALC, the present study was aimed to investigate the effects of ALC on KET-induced neurotoxicity and the underlying mechanism in vitro. Our data revealed that co-treatment with ALC and KET was more detrimental to cell viability than KET single treatment in both PC12 cells and primary cultured rat cortical neurons. Furthermore, ALC exacerbated KET-induced apoptosis characterized by morphological changes and the sub-G1 phase increase, which were mitigated by the pretreatment of CNQX, a known alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainite (KA) receptor antagonist. In addition, ALC and KET co-treatment led to intracellular Ca2+ overload, down-regulation of p-Akt, p-CREB, PKA, CaMK-IV, Bcl-2 and BDNF expression and up-regulation of cleaved caspase-3 and Bax expression, which can be attenuated by CNQX pretreatment. These results indicate that the potentiation of ALC on KET-induced neurotoxicity was related to the down-regulation of CREB-related pathways. Our present study also indicates that ALC and KET co-abuse might cause serious neurotoxicity which should be conveyed to the public and drew enough attention.

Enhancing cell nucleus accumulation and DNA cleavage activity of anti-cancer drug via graphene quantum dots.

Graphene quantum dots (GQDs) maintain the intrinsic layered structural motif of graphene but with smaller lateral size and abundant periphery carboxylic groups, and are more compatible with biological system, thus are promising nanomaterials for therapeutic applications. Here we show that GQDs have a superb ability in drug delivery and anti-cancer activity boost without any pre-modification due to their unique structural properties. They could efficiently deliver doxorubicin (DOX) to the nucleus through DOX/GQD conjugates, because the conjugates assume different cellular and nuclear internalization pathways comparing to free DOX. Also, the conjugates could enhance DNA cleavage activity of DOX markedly. This enhancement combining with efficient nuclear delivery improved cytotoxicity of DOX dramatically. Furthermore, the DOX/GQD conjugates could also increase the nuclear uptake and cytotoxicity of DOX to drug-resistant cancer cells indicating that the conjugates may be capable to increase chemotherapy efficacy of anti-cancer drugs that are suboptimal due to the drug resistance.