Metastasis of lung cancer?

BACKGROUND: Sarcoidosis is a multi-system, idiopathic, inflammatory disorder that affects the lungs in over 90% of patients. The incidence of bone lesions in sarcoidosis is only 1-13%. CASE REPORT: This study describes a 60-year-old woman with a previous history of thyroid cancer, and a more recent diagnosis of lung cancer with suspicious metastatic lesions, which were confirmed to be sarcoidosis. CONCLUSION: This case suggests that pulmonary neoplasms and pulmonary sarcoidosis can coexist and be easily confused. When lung cancer is accompanied by symmetric hilar lymph node enlargement and multiple lung nodules, sarcoidosis should be considered in addition to metastasis, and a biopsy should be performed for confirmation.

A PW12/Ag functionalized mesoporous silica-coated magnetic Fe3O4 core-shell composite as an efficient and recyclable photocatalyst.

The novel composite, Fe3O4@SiO2@mSiO2-PW12/Ag, was successfully prepared by in situ loading Ag nanoparticles (Ag NPs) on the surface of grafted phosphotungstate (denoted as PW12) Fe3O4@SiO2@mSiO2via a photoreduction deposition method. PW12 not only acts as a reducing agent and stabilizer for Ag NPs but also as a bridge to link Ag NPs and the SiO2 shell in the loading process. Its activity toward the photodegradation of methyl orange (MO) and photoreduction of Cr2O72- anions was evaluated. Experimental results showed that Fe3O4@SiO2@mSiO2-PW12/Ag with 5.3 wt% Ag loading and 18.65 wt% of PW12 exhibits the highest photocatalytic efficacy, and complete degradation of MO and 91.2% photoreduction of Cr(vi) were realized under simulated sunlight for 75 min, respectively. The enhanced catalytic activities of the composite are due to its high specific surface area, the synergistic effect among the components and the formation of a heterojunction of PW12/Ag. The possible enhanced photocatalytic mechanism is proposed. The catalyst is durable and can be easily recovered using a magnet for recycling without a significant loss of catalytic activity.

Bufalin Induces Glioma Cell Death by Apoptosis or Necroptosis.

INTRODUCTION: Bufalin is a component of Chinese traditional medicine, Chansu, which is reported to induce cell death among various kinds of tumors. Apoptosis evasion is a common problem of cancer treatment. MATERIALS AND METHODS: The proliferation of U-87 and U-373 treated by bufalin combined with or without apoptosis inhibitor was detected by MTT assay. The protein levels related to apoptosis and necroptosis were measured by Western blotting. Immunoprecipitation (IP) was applied for monitoring the formation of necrosome. The gene knockdown by CRISPR/Cas9 was applied to determine the roles of the proteins in apoptosis and necroptosis. RESULTS: In this study, we found that bufalin could induce apoptosis or necroptosis when U-87 and U-373 escaped from apoptosis. Bufalin triggered cell death by upregulating tumor necrosis factor (TNF) -α, TNF receptor 1 (TNFR1) and receptor-interacting protein 1 (RIPK1). Antagonizing cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2 were also contributory. Caspase-8 activation led to apoptosis. When caspase-8 was functionally lost, necrosome consisted of RIPK1, receptor-interacting protein 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) formed and necroptosis happened. The knockdown of above genes or the drug treatment confirmed the mechanism of bufalin-induced cell death. Cytotoxicity of bufalin to caspase-8 knockdown cell lines made control cell lines more sensitive to bufalin in their mixture. DISCUSSION: The cytotoxicity of bufalin to U-87 and U-373 was by inducing apoptosis or necroptosis when they were sensitive to apoptosis or not. The results indicated that seeking for treatments that could induce apoptosis and necroptosis was a good solution for the tumor evasion of apoptosis.

ROS-augmented and tumor-microenvironment responsive biodegradable nanoplatform for enhancing chemo-sonodynamic therapy.

Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.

[Establishment of neuritis migration model induced by Slit 2N and silk fibroin mixture in the rat hippocampal neurons in vitro].

OBJECTIVE: To explore a simply feasible and affordable method to establish neuritis migration model induced by Slit 2N and silk fibroin mixture in the rat hippocampal neurons in vitro. METHODS: Neurons were derived from SD rat hippocampal tissues and cultured with a special cell culture-plate in vitro. The cultured neurons were divided into four groups, named as control group, pure silk fibroin, pure Slit 2N and Slit 2N mixture with silk fibroin (mixture group), and 50 different neurons were randomly selected in each group. Moreover, we photographed and recorded the soma coordinate and added the silk fibroin, Slit 2N and mixture to each neurite with a distance of 100 µm, except control group. Record again after 30 min. Property and positive rate of cells were identified by immunofluorescence staining. RESULTS: Neurites of the pure Slit 2N group and the mixture group became shorter, and there was no significant change in the pure silk fibroin and control groups. The results showed that the average duration and length difference before and after changed were in descending order of mixture group, Slit 2N group, silk fibroin group (P<0.05), and the silk fibroin and control groups were no significant change (P>0.05). The positive rate of MAP-2 in four groups was more than 90%. CONCLUSIONS: There were no significant effects of Silk fibroin on induced by Slit 2N in rat hippocampal neuron migration. It had an effect on reducing Slit 2N diffusion rate and extending its working time. It provides an advantageous construction method in vitro on based 3D directed neural repair for the treatment of central nervous system diseases.

Co-culture of oligodendrocytes and neurons can be used to assess drugs for axon regeneration in the central nervous system.

We present a novel in vitro model in which to investigate the efficacy of experimental drugs for the promotion of axon regeneration in the central nervous system. We co-cultured rat hippocampal neurons and cerebral cortical oligodendrocytes, and tested the co-culture system using a Nogo-66 receptor antagonist peptide (NEP1-40), which promotes axonal growth. Primary cultured oligodendrocytes suppressed axonal growth in the rat hippocampus, but NEP1-40 stimulated axonal growth in the co-culture system. Our results confirm the validity of the neuron-oligodendrocyte co-culture system as an assay for the evaluation of drugs for axon regeneration in the central nervous system.

Gold nanorods-based FRET assay for ultrasensitive detection of DNA methylation and DNA methyltransferase activity.

A fluorescence method for the detection of DNA methylation and the assay of methyltransferase activity is proposed using gold nanorods as a fluorescence quencher on the basis of fluorescence resonance energy transfer. It is demonstrated that this method is capable of detecting methyltransferase with a detection limit of 0.25 U mL(-1), which might make this method a good candidate for monitoring DNA methylation in the future.

Incorporation of M(H2O)6(2+) between layers {M(H2O)2Ru2(CO3)4Cl2}n(2n-) (M = Zn, Mn): syntheses, structures and magnetic properties.

Isostructural heterometallic diruthenium carbonates KM(H2O)6[M(H2O)2Ru2(CO3)4Cl2]·4H2O [M = Zn (1) and Mn (2)] were synthesized from the reaction of the precursors [Ru2(CO3)4Cl2](5-) and transitional metal ions in aqueous solution. Complexes 1 and 2 show layered structures in which Ru2(II,III) units are linked by four octahedral environment M(H2O)2(2+) ions in a cross fashion and vice versa giving a negative bimetallic square grid layer {M(H2O)2Ru2(CO3)4Cl2}n(3n-). M(H2O)6(2+) ions, linked by K(+) forming zigzag chain {KM(H2O)6}n(3+), are located in the void spaces between the layers. The adjacent bimetallic carbonate layers are connected with K-O and K-Cl bonds, and hydrogen bonding, forming a supramolecular 3D framework structure. Their magnetic properties were characterized in detail, and intralayer ferromagnetic coupling between the Ru2 dimer and Mn(2+) ion, as well as long-range ordering (Tc = 5.2 K) coexistence of domain movement behavior were observed for complex 2.

Cadmium diruthenium(II,III) carbonates showing diverse magnetism behavior arising from variety configuration of [Ru2(CO3)4]n(3n-) layer.

Two hetero-metallic carbonates, namely KCd(H2O)3Ru2(CO3)4·4H2O (1) and KCd(H2O)3Ru2(CO3)4·3.5H2O (2), have been synthesized in a neutral aqueous solution. Both of the 3D dimensional structured complexes contain mixed-valent diruthenium(II,III) carbonate paddlewheel cores of Ru2(II,III)(CO3)4(3-) that are connected to each other in trans- or cis-modes by carbonate oxygen atoms, forming rectangular square-grid and isomeric parallelogram layers [Ru2(CO3)4]n(3n-) in 1 and 2, respectively. The reaction temperature is found to play an important role in directing the final products with particular topologies and their layered structural diversity is due to the various linking modes between the Ru2(CO3)4(3-) units. The magnetic studies show that ferromagnetic interactions are propagated between the diruthenium units in both complexes 1 and 2 but their magnetic properties differ at low temperatures, in which the trans linking mode parallelogram layer [Ru2(CO3)4]n(3n-) in complex 2 leads to long-range magnetic ordering below 4.0 K. However, no Curie ordering down to 1.8 K is detected for complex 1 containing the isomeric rectangle square-grid layer linking in the cis mode.

Electrochemical strategy for sensing DNA methylation and DNA methyltransferase activity.

The present work demonstrates a novel signal-off electrochemical method for the determination of DNA methylation and the assay of methyltransferase activity using the electroactive complex [Ru(NH3)6](3+) (RuHex) as a signal transducer. The assay exploits the electrostatic interactions between RuHex and DNA strands. Thiolated single strand DNA1 was firstly self-assembled on a gold electrode via Au-S bonding, followed by hybridization with single strand DNA2 to form double strand DNA containing specific recognition sequence of DNA adenine methylation MTase and methylation-responsive restriction endonuclease Dpn I. The double strand DNA may adsorb lots of electrochemical species ([Ru(NH3)6](3+)) via the electrostatic interaction, thus resulting in a high electrochemical signal. In the presence of DNA adenine methylation methyltransferase and S-adenosyl-l-methionine, the formed double strand DNA was methylated by DNA adenine methylation methyltransferase, then the double strand DNA can be cleaved by methylation-responsive restriction endonuclease Dpn I, leading to the dissociation of a large amount of signaling probes from the electrode. As a result, the adsorption amount of RuHex reduced, resulting in a decrease in electrochemical signal. Thus, a sensitive electrochemical method for detection of DNA methylation is proposed. The proposed method yielded a linear response to concentration of Dam MTase ranging from 0.25 to 10UmL(-1) with a detection limit of 0.18UmL(-1) (S/N=3), which might promise this method as a good candidate for monitoring DNA methylation in the future.

The protective effects of 6-CySeCD with GPx activity against UVB-induced injury in HaCaT cells.

BACKGROUND: The generation of harmful reactive oxygen species (ROS) induced by UVB irradiation could induce cell apoptosis and change the cell cycle. 6A,6A'-dicyclohexylamine-6B,6B'-diselenide-bis-ß-cyclodextrin (6-CySeCD) is a novel glutathione peroxidase (GPx; EC 1.11.1.9) mimic. The aim of this study was to investigate the anti-oxidative effects of 6-CySeCD in cultured immortalised human keratinocyte cells (HaCaT). METHODS: HaCaT cells were treated with 30 mJ/cm(2) UVB to establish a damage model. The cultured HaCaT cells were randomly assigned to the control, UVB and treatment groups. The treatment group was incubated with 20 µmol/L of GPx mimics before UVB irradiation. Cell viability was detected by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the level of lipid peroxidation was determined by the formation of malondialdehyde (MDA), DNA fragmentation was observed using agarose gel electrophoresis and the levels of intracellular ROS and cell cycle progression were measured by flow cytometry. RESULTS: The levels of cytotoxicity, intracellular ROS, lipid peroxidation and oxidative DNA damage significantly increased after UVB irradiation in the HaCaT cells. UVB irradiation caused pre-G1 -phase arrest in HaCaT cells and significantly reduced the number of HaCaT cells in the S phase. The GPx mimics 6-CySeCD and 2-phenyl-l,2-benzisoselenazol-3(2H)-one (ebselen) significantly blocked UVB-induced apoptosis and changed the cell cycle of the HaCaT cells. The blocked effect of pretreatment 6-CySeCD in UVB-irradiated HaCaT cells was better than that of pretreatment with ebselen. CONCLUSION: 6-CySeCD can relieve the damage induced by UVB irradiation in HaCaT cells.

A simple and label-free electrochemical biosensor for DNA detection based on the super-sandwich assay.

The focus of this work was on designing a label-free DNA biosensor based on a super-sandwich assay using the electrochemical impedance spectroscopy technique. For this purpose, we designed a signal-up configuration whose linker probes could hybridize with two regions of the target DNA. In this configuration, the presented target DNA would effectively decrease the electron transfer, which would improve the sensitivity of the sensor. Ultimately, we employed gel electrophoresis to further confirm the formation of the proposed super-sandwich structure.

A diruthenium soft ferromagnet showing T(c) = 3.0 K: Mn4(H2O)16H[Ru2(CO3)4]2[Ru2(CO3)4(H2O)2]·11H2O.

A three-dimensional CO(3)(2-)-bridged Mn(II)-Ru(2)(II,III) complex, Mn(4)(H(2)O)(16)H[Ru(2)(CO(3))(4)](2)[Ru(2)(CO(3))(4)(H(2)O)(2)]·11H(2)O (1), was synthesized by self-assembling Ru(2)(CO(3))(4)(3-) paddle-wheel precursors and Mn(2+) cations. It contains an unprecedented layer [Ru(2)(CO(3))(4)](n)(3n-) with (4,4) network. The ferromagnetic coupling between spin centers results in ordering below 3.0 K.

Synthesis and biological evaluation of azobicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes.

A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.

Synthesis and biological evaluation of bicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes.

A series of novel bicyclo[3.3.0]octane derivatives have been synthesized and found to be dipeptidyl peptidase 4 (DPP-4) inhibitors. Compounds 10a and 10b demonstrate good efficacies in oral glucose tolerance tests.

A trifunctional enzyme with glutathione S-transferase, glutathione peroxidase and superoxide dismutase activity.

Superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione S-transferase (GST) and glutathione reductase (GR) play crucial roles in balancing the production and decomposition of reactive oxygen species (ROS) in living organisms. These enzymes act cooperatively and synergistically to scavenge ROS, as not one of them can singlehandedly clear all forms of ROS. In order to imitate the synergy of the enzymes, we designed and generated a recombinant protein, which comprises of a Schistosoma japonicum GST (SjGST) and a bifunctional 35-mer peptide with SOD and GPX activities. The engineered protein demonstrated SOD, GPX and GST activities simultaneously. This trifunctional enzyme with SOD, GPX and GST activities is expected to be the best ROS scavenger.

[A discussion on the biological evaluation method for nanosilver antibiotic devices for gynecological external use].

Nanosilver antibiotic devices for gynecological external use are the third-class products of medical devices, whose biological safety and efficiency should be strictly controlled. But there is not yet the national standard or industry standard for the products to control the production process, so their testing method of biological evaluation mainly refers to GB/T16886 "The Guide to Implementation of Biological Evaluation of Medical Devices". To control the biological safety effectively, it's necessary to work out the testing items and methods of the biological evaluation for such products.

[The clinical characteristics of acute severe high-altitude diseases in indigenous Tibetans].

OBJECTIVE: To describe the incidence and clinical characteristics of acute severe high-altitude diseases in indigenous Tibetans. METHODS: The medical records of indigenous Tibetan patients with high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE), who were treated in this hospital from June of 1956 to June of 2005, were retrospectively reviewed. RESULTS: A total of 3 184 cases of high-altitude disease were recorded in this period. Twenty four patients (0.75%, 24/3 184), 21 with HAPE and 3 with HACE, were indigenous Tibetans. Risk factors or precipitating factors were found in all the 24 cases, including getting into even higher altitude, exertion, cold, and alcohol drinking. From clinical symptoms, physical signs and laboratory examinations, it was found that 9 cases were complicated with multi-organ dysfunction. CONCLUSION: Indigenous Tibetans who travel between the plateau and the plain or to even higher altitude can suffer from hypoxic injury, even acute severe high-altitude disease, which may be complicated by multi-organ dysfunction.

[Hemodynamic effects of aminophylline and nifedipine in patients with high altitude pulmonary edema].

AIM: To evaluate the hemodynamic effects of aminophylline and nifedipine in patients with HAPE. METHODS: 10 patients with HAPE undergone Swan-Ganz catheter. The parameters of hemodynamics and arterial blood gases in HAPE were measured before and after administration of nifedipine 20 mg sublingually and aminophylline 0.25 g intravenously respectively. RESULTS: After administering 0.25 g aminophylline the mPAP and PVR significantly decreased, the cardiac output and the level of PaO2, SaO2 increased obviously, the mSAP, HR did not change so much. After using 20 mg nifedipine, the mPAP, PVR and mSAP also decreased, while the cardiac output, HR and the level of PaO2, SaO2 did not show any changes. CONCLUSION: Both of aminophylline and nifedipine can attenuate pulmonary hypertension in patients with HAPE, but the effect of aminophylline was better than the effect of nifedipine.