Plasmapheresis in the treatment of multi-drug intoxication involving levothyroxine sodium and calcium channel blockers: a case report.

Plasmapheresis, a procedure used to remove large molecular weight, protein-bound molecules from a patient's blood, has been shown to be useful in some cases of drug overdose. Levothyroxine sodium intoxication may result from the intentional or accidental ingestion of excessive amounts of the hormone, which can trigger a thyroid storm. However, case reports about the extremely large dose of 15,000 µg of thyroxine intoxication are extremely rare, and even combined with calcium channel blockers (CCBs) poisonings. We present a case of an intentional poisoning with high doses of thyroxine, diltiazem and amlodipine successfully treated with plasma exchange. A 40-year-old woman was admitted showing unconsciousness and sustained hypotension with high levels of thyroid hormones (THs). It was discovered that she had secretly ingested at least 15,000 µg of levothyroxine sodium and CCBs with unknown amounts of diltiazem and amlodipine. Following plasmapheresis, the levels of TH declined dramatically after each of the 4 sessions, with hemodynamics gradually stabilizing and mental state improving. The early and timely use of plasmapheresis appears to be a vital therapeutic tool for the management of acute and severe forms of l-thyroxine and CCB intoxication. Its use can prevent thyroid storm and reverse the disturbances in the patient's hemodynamic status.

Overexpression of lncRNA TUSC7 reduces cell migration and invasion in colorectal cancer.

Colorectal cancer (CRC) is a highly heterogeneous disease worldwide. Long non­coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) plays a crucial role in the development of several cancers. However, the role of TUSC7 in the tumorigenesis of CRC has not been explored. The TUSC7­overexpressing CRC cell lines SW480 and CaCo­2 were generated to investigate the effects of TUSC7 on the growth, migration, invasion and epithelial­mesenchymal transition (EMT) of CRC cells. CCK­8, wound­healing and Transwell assays were used to evaluate CRC cell proliferation, migration and invasion. The mRNA and protein expression of TUSC7 were detected by quantitative real­time PCR and immunoblotting, respectively. In the present study, we observed that the expression of TUSC7 was decreased in CRC cells compared to the expression in the normal colon epithelial cell line NCM460. Moreover, overexpression of TUSC7 inhibited CRC cell proliferation, metastasis, invasion and EMT. These findings indicated that TUSC7 is involved in CRC development.

UHRF1 mediates cell migration and invasion of gastric cancer.

Gastric cancer (GC) is a common highly aggressive malignant tumor in worldwide. Ubiquitin-like with PHD and ring-finger protein 1 (UHRF1) has a key role in several kinds of cancers development. However, the biology effect of UHRF1 on the tumorigenesis of GC remains unclear. In this research, the role of UHRF1 in the growth, migration, invasion and apoptosis and the underlying mechanisms were investigated in MGC803 and SGC7901 cells. The UHRF1 knockdown MGC803 and SGC7901 cell lines were used to investigate the roles of UHRF1 on GC cell growth, migration, invasion and apoptosis. The growth, migration and invasion rate of UHRF1 knockdown cells was lower than that of the control. Moreover, ROS generation and caspase-3/caspase-9 activities increased in UHRF1 knockdown cells. And mitochondrial membrane potential decreased in UHRF1 knockdown cells. These findings indicated that UHRF1 promoted the growth, migration and invasion of MGC803 and SGC7901 cells and inhibited apoptosis via a ROS-associated pathway.

Facile synthesis by a covalent binding reaction for pH-responsive drug release of carboxylated chitosan coated hollow mesoporous silica nanoparticles.

In this study, a promising drug nano-carrier system consisting of mono-dispersed and pH sensitive carboxylated chitosan-hollow mesoporous silica nanoparticles (Ccs-HMSNs) suitable for the treatment of malignant cells was synthesised and investigated. At neutral pH, the Ccs molecules are orderly aggregated state, which could effectively hinder the release of loaded drug molecules. However, in slightly acidic environment, Ccs chains are heavily and flexibly entangled in gel state, which would enhance the subsequent controlled release of the loaded drug. Using doxorubicin hydrochloride (DOX•HCl) as the drug model, their results demonstrated that the system had an excellent loading efficiency (64.74 µg/mg Ccs-HMSNs) and exhibited a pH-sensitive release behaviour. Furthermore, confocal laser scanning microscopy revealed that the Ccs-HMSNs nanocomposite could effectively deliver and release DOX•HCl to the nucleus of HeLa cells, thereby inducing apoptosis. In addition, MTT assay also confirmed that DOX•HCl loaded Ccs-HMSNs (DOX•HCl@Ccs-HMSNs) exhibited a good anticancer effect on HeLa cells with a time-dependent manner. Finally, haemolysis experiment showed Ccs-HMSNs had no haemolytic activity at all the tested concentrations (5-320 µg/mL). Thus, this biocompatible and effective nano-carrier system will have potential applications in controllable drug delivery and cancer therapy.

PM2.5 exposure decreases viability, migration and angiogenesis in human umbilical vein endothelial cells and human microvascular endothelial cells.

Previous studies have confirmed that exposure to particulate matter with a diameter of ≤2.5 µm (PM2.5) is associated with inflammation. PM2.5 decreases cardiac cell viability and increases apoptosis through overproduction of reactive oxygen species (ROS). In the present study, the role of PM2.5 in ECs was investigated in vitro. Human umbilical vein endothelial cells and human microvascular endothelial cells (ECs) were incubated with PM2.5 (100­800 µg/ml) to investigate the effects of PM2.5 on EC viability, migration, tube formation and intracellular levels of ROS. Cell viability and cell apoptosis were determined by MTT assay and flow cytometry analysis. Cell migration was assessed using a Boyden chamber assay, and tube formation was determined by matrigel assay. Tumor necrosis factor­α and interleukin­8 levels were measured by ELISA, and ROS levels were assessed with 2',7'­dichlorofluorescin diacetate. The results indicated that PM2.5 decreases EC viability and increases EC apoptosis in a concentration­dependent manner. PM2.5 also decreased EC tube formation in a dose­dependent manner. The results also demonstrated that PM2.5 suppresses adhesion to EC extracellular matrix proteins. Furthermore, PM2.5 exposure significantly induced ROS generation, indicative of oxidative stress. Finally, it was demonstrated that PM2.5 decreased angiogenesis in vivo. These results suggested that repeated exposure to PM2.5 induces vascular inflammation.

Curcumin-Loaded TPGS/F127/P123 Mixed Polymeric Micelles for Cervical Cancer Therapy: Formulation, Characterization, and InVitro and InVivo Evaluation.

Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.

Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease.

BACKGROUND: Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD. OBJECTIVE: To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk. METHODS: A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs. RESULTS: Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10­3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2. CONCLUSION: These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD.

Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease / Hipometilação do Promotor de Interleucina-6 Associada com Risco de Doença Arterial Coronariana

Abstract Background: Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD. Objective: To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk. Methods: A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs. Results: Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10‑3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2. Conclusion: These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD.

Resumo Fundamento: Interleucina-6 (IL-6) está implicada na patogênese de doença arterial coronariana (DAC), sendo sua expressão associada com redução da metilação de DNA do promotor do seu gene. Entretanto, não há dados sobre metilação do promotor de IL-6 e risco de DAC. Objetivo: Verificar se a metilação do promotor de IL-6 medida no DNA de leucócitos sanguíneos acha-se associada com risco de DAC. Métodos: este estudo arrolou 212 casos com DAC e 218 controles. Metilação em dois sítios de CpG no promotor de IL-6 foi medida por pirosequenciamento de bissulfito, sendo a metilação média de IL-6 calculada pela média das medidas de metilação dos dois CpGs. Resultados: A média do nível de metilação no promotor de IL-6 nos casos de DAC foi significativamente mais baixa do que nos controles (p = 0,023). Análise de regressão logística mostrou associação inversa entre metilação de IL-6 e risco de DAC. As razões de chance (OR) de DAC para indivíduos no segundo e no primeiro (mais baixo) tercis de metilação de IL-6 foram 1,87 (IC 95%: 1,10-3,20) e 2,01 (IC 95%: 1,19-3,38) (ptrend = 0,013), respectivamente, comparadas à de indivíduos no terceiro (mais alto) tercil. As estimativas de risco relacionado à hipometilação de IL-6 tenderam a ser mais fortes para infarto agudo do miocárdio (ptrend = 0,006). Análise com especificidade de posição de CpG mostrou que hipometilação na posição 1 conferiu maior elevação no risco de DAC do que na posição 2. Conclusão: Tais achados sugerem que a hipometilação de DNA do promotor de IL-6 está associada com elevado risco de DAC, especialmente para infarto agudo do miocárdio. Os dois CpGs distintos no promotor de IL-6 podem contribuir de modo diferente para o desenvolvimento de DAC.

Proteomic characteristics of circulating microparticles in patients with newly-diagnosed type 2 diabetes.

OBJECTIVE: This study aimed to evaluate the proteomic characteristics of plasma microparticles (MPs) from patients with newly diagnosed type 2 diabetes (T2DM). METHODS: The subjects comprised eight male T2DM patients recruited between December 2013 and March 2014, as well as eight age and sex-matched healthy controls enrolled during the same period. Plasma microparticles (MPs) were extracted from the blood of each subject, and subjected to proteomics analysis using label-free methods. Bioinformatic analyses were performed using specialized software. RESULTS: 3,148 unique peptides and 496 proteins were identified, among these, 46 proteins were differentially expressed between the two groups. Among these 46 candidates, 20 proteins had higher expression in T2DM group compared with the control group, whereas 3 proteins displayed lower expression. There were 17 proteins only detected in T2DM group, and 6 proteins only detected in the control group. Gene ontology (GO) analysis revealed significant differences between the two groups in some functional nodes, including neutrophil accumulation, chemokine production, platelet activation, and blood coagulation. Pathway analysis showed that proteins involved in platelet activation, cell adhesion, focal adhesion, and extracellular matrix-receptor interaction were differentially expressed between the 2 groups. Network analysis indicated that ubiquitin was the protein with the highest degree of connectivity. CONCLUSIONS: Blood MPs from T2DM patients are enriched in proteins involved in platelet activation, cell adhesion, and inflammation. Therefore, MPs in T2DM patients might be associated with hypercoagulable state in diabetic patients and the development of diabetic complications.

Association of depression with pre-diabetes, undiagnosed diabetes, and previously diagnosed diabetes: a meta-analysis.

We performed a meta-analysis to analyze the associations of depression with pre-diabetes (PreDM), undiagnosed diabetes (UDM), and previously diagnosed diabetes (PDM), and whether the association was affected by important study characteristics. We searched relevant articles published in PubMed and EMBASE up to August, 2015. Studies reporting cross-sectional associations of depression with PreDM, UDM, or PDM compared with normal glucose metabolism (NGM) were included. Odds ratios (ORs) were pooled with random-effect and fixed-effect models. Subgroup analyses by sex, study mean age, different degrees of adjustment, publication year, quality score, and depression assessment scales were also performed. Twenty studies were eligible and included in current analysis. Summary estimates showed that compared with NGM individuals, prevalence of depression was moderately increased in PreDM (random-effect odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.03-1.19) and UDM (OR 1.27, 95 % CI 1.02-1.59), and markedly increased in PDM (OR 1.80, 95 % CI 1.40-2.31). Subgroup analyses showed that the positive association remained only among studies with mean age <60 years old but not among those with mean age ≥60 years old. Summary estimates of ORs with cardiovascular disease adjustment substantially attenuated the association. Our findings suggested that risk of prevalent depression was gradually increased with the deterioration of glucose metabolism among younger age groups but not among older age groups. Comorbid cardiovascular diseases might be an important intermediate factor underlying the association between depression and diabetes.

pH sensitive nano layered double hydroxides reduce the hematotoxicity and enhance the anticancer efficacy of etoposide on non-small cell lung cancer.

Etoposide (VP16), used for the treatment of many carcinomas, can cause leukopenia, thrombocytopenia and hair loss. To overcome the side effects and achieve target therapy, layered double hydroxides (LDHs), a pH sensitive layered double hydroxide nanohybrid, was used here as a nano-carrier. The functions of LDHs-VP16 on non-small cell lung cancer (NSCLC) were firstly explored both in vitro and in vivo. In A549 cell line, LDH-VP16 induced apoptosis 2.3-fold as that of plain VP16 by targeting to mitochondrial, stocking cells in G1 phase. The cellular uptake demonstrated the delivery of LDH for VP16 to pass through the membrane and accumulate in mitochondria. As a carrier, LDH greatly decreased the liver toxicity and hematotoxicity of VP16. The detected liver parameters, including glutamic-oxaloacetic transaminase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), were all turn back to normal range after the delivery of LDH, except ALP. In vivo, LDH-VP16 reduced A549 tumor growth significantly by 60.5%, whereas native VP16 exerted no significant anticancer activity. In LDH-VP16 treated mice, the AUC was increased by 6.26 folds as the native drug, and t1/2 of LDH-VP16 was prolonged from 6.68 to 98.78h. LDH-VP16 showed a targeting effect, which largely increase the concentration in tumor and lung. The phosphorylation antibody array and Western Blot of proteins from xenografts revealed that PI3K-AKT signaling was suppressed in the LDH-VP16 treated tumor, while in VP16 treated mice, ERBB signaling pathway was involved. These results suggested that LDH-VP16 diminishes hematotoxicity, targets NSCLC tumor, performs more effectively than VP16, and different signaling pathway is involved compared to VP16. STATEMENT OF SIGNIFICANCE: This paper explored that nano-sized layered double hydroxide (LDH) could be used as a pH sensitive delivery system to overcome hematotoxicity and enhance the bioavailability and anticancer efficacy of etoposide (VP16) against non small cell lung cancer, which was not reported before, as the best of our knowledge. We found that the liver and hematotoxicity is nearly recovered after the loading of VP16 in pH sensitive LDH, which prongs the half time from 6.68h to 98h, helps target VP16 to tumor and lung, and protects white blood cells by its pH sensitive and nano-size property. LDH-VP16 achieve markedly performance on non-small cell lung cancer by targeting to mitochondria of A549 cells in vitro and effectively inhibiting the PI3K-AKT signaling pathway in vivo. The inhibition ratio of VP16 on A549 tumor growth is increased from less than 20% (no significance compared to control) to 60.5% after the delivery of LDH. This work provides a novel system for the safe and efficient use of etoposide on non-small cell lung cancer and explores the mechanism of the function of nano carrier in cancer therapy both in vitro and in vivo.

Discovery of Xuebijing Injection Exhibiting Protective Efficacy on Sepsis by Inhibiting the Expression of HMGB1 in Septic Rat Model Designed by Cecal Ligation and Puncture.

Xuebijing (XBJ) injection is a complex traditional Chinese prescription that has been widely used to treat sepsis in China. However, its underlying mechanisms on sepsis still remain uninvestigated. In this study, 150 male Sprague Dawley rats were randomly divided into a normal control group, cecal ligation and puncture (CLP) group, CLP+XBJ group, and CLP+gibberellic acid group. Each of them contained 3 subgroups of different treatment periods (12, 24, and 48 hours after injection, respectively). The mRNA expression of HMGB1 in liver tissue of the 4 groups was calculated by the semiquantitative reverse-transcription polymerase chain reaction. The level of IL-6, IL-10, and TNF-α was determined by an enzyme-linked immunosorbent assay. Immunohistochemical analysis for HMGB1 showed the effect of XBJ on infiltration of inflammatory cells. The mRNA expression of HMGB1 in liver tissue in CLP+XBJ and CLP+gibberellic acid groups was lower than that in the CLP group. The levels of IL-6, IL-10, and TNF-α were decreased at the each monitored time point. All these results indicated that XBJ exhibits protective efficacy on sepsis by inhibiting the expression of HMGB1.

Clinical features of ischemic hepatitis caused by shock with four different types: a retrospective study of 328 cases.

The aim of the study was to investigate the clinical features of ischemic hepatitis due to shock with four different types (allergic shock, hypovolemic shock, septic shock, and cardiogenic shock). A total of 328 patients (200 males, 128 females, mean age, 65.84 ± 15.21 years old, range, 15-94 years) diagnosed with shock in Tongji Hospital were retrospectively investigated from Jun 2008 to Feb 2010. The parameters of liver function test, including alanine aminotransferanse (ALT), aspartate aminotransferanse (AST), lactate dehydrogenase (LDH), total bilirubin (TB), alkaline phosphatase (ALP) and γ-glutamyltransferase (γ-GT), were recorded and analyzed. Besides, the serum levels of C-reactive protein (CRP) and brain natriuretic peptide (BNP) were also measured and relevant correlation analysis was conducted. Among all the cases, 242 (73.8%) patients developed ischemic hepatitis. The mortality of shock patients combined with ischemic hepatitis was significantly higher than the total mortality (26.0% vs 23.8%, P < 0.05). The incidence of hepatic damage was highest in the septic shock (87.5%), while the lowest in thehypovolemic shock (49.4%). The sensitivity of ALT elevation was higher than that of AST. In addition, CRP was positively correlated with the levels of liver function parameters in the septic shock and BNP was positively correlated with that in the cardiogenic shock. Ischemic hepatitis is a common complication of shock, increasing the mortality of shock patients. The septic shock is the most common cause of hepatic damage in shock patients. CRP may be a useful predictor for septic shock, while BNP may be a useful predictor for cardiogenic shock.

Increased Expressions of Integrin Subunit ß1, ß2 and ß3 in Patients with Acute Infection.

OBJECTIVE: Our previous studies have shown that integrin subunits ß1, ß2 and ß3 were the core proteins of venous thrombi and potential useful biomarker of venous thromboembolism (VTE). Patients with acute infection have a high risk of VTE. In this study we explored that is there any relevance between core proteins and acute infection. METHODS: A total of 230 patients (112 females) with clinically proven acute infection in the emergency unit were recruited into this study, meanwhile 230 patients without acute infection matched in sex and age were recruited as control group. Flow cytometry was done to measure the expressions of blood integrin ß1, ß2, ß3 and cellular immunity (CD3, CD4, CD8, CD4/CD8, CD16CD56 and CD19). The association degree between increased core proteins and acute infection was analyzed by calculating the relative risk (RR). RESULTS: The expression of integrin ß1, ß2 and ß3 was markedly increased in patients with acute infection (P=0.000, 0.000 and 0.015, respectively). The relative risk ratio (RR) of increased integrin ß1, ß2 and ß3 in acute infection patients was 1.424 (95%CI: 1.156-1.755, P=0.001), 1.535 (95%CI: 1.263-1.865, P=0.000) and 1.20 (95%CI: 0.947-1.521, P=0.148), respectively. Combined integrin ß1, ß2 and ß3 analysis showed that the relative risk ratio (RR) of increased in patients with acute infection was 2.962 (95%CI: 1.621-5.410, P=0.001), and this relative risk (RR) rise to 3.176 (95%CI: 1.730-5.829, P=0.000) in patients with respiratory tract infection (RTI). CONCLUSION: As the core proteins of venous thrombi, integrinß1, ß2 and ß3 were markedly increased expression in patients with acute infection, which maybe explain the increased risk of VTE in acute infection patients. A weakened immune system could be the basic condition of VTE occurrence.

Layered double hydroxide nanoparticles promote self-renewal of mouse embryonic stem cells through the PI3K signaling pathway.

Embryonic stem cells (ESCs) hold great potential for regenerative medicine due to their two unique characteristics: self-renewal and pluripotency. Several groups of nanoparticles have shown promising applications in directing the stem cell fate. Herein, we investigated the cellular effects of layered double hydroxide nanoparticles (LDH NPs) on mouse ESCs (mESCs) and the associated molecular mechanisms. Mg-Al-LDH NPs with an average diameter of ∼100 nm were prepared by hydrothermal methods. To determine the influences of LDH NPs on mESCs, cellular cytotoxicity, self-renewal, differentiation potential, and the possible signaling pathways were explored. Evaluation of cell viability, lactate dehydrogenase release, ROS generation and apoptosis demonstrated the low cytotoxicity of LDH NPs. The alkaline phosphatase activity and the expression of pluripotency genes in mESCs were examined, which indicated that exposure to LDH NPs could support self-renewal and inhibit spontaneous differentiation of mESCs under feeder-free culture conditions. The self-renewal promotion was further proved to be independent of the leukemia inhibitory factor (LIF). Furthermore, cells treated with LDH NPs maintained the potential to differentiate into all three germ layers both in vitro and in vivo through formation of embryoid bodies and teratomas. In addition, we observed that LDH NPs initiated the activation of the PI3K/Akt pathway, while treatment with the PI3K inhibitor LY294002 could block the effects of LDH NPs on mESCs. The results confirmed that the promotion of self-renewal by LDH NPs was associated with activation of the PI3K/Akt signaling pathway. Altogether, our studies identified a new role of LDH NPs in maintaining self-renewal of mouse ES cells which could potentially be applied in stem cell research.

Fatal cases of human infection with avian influenza A (H7N9) virus in Shanghai, China in 2013.

We retrospectively reviewed the medical records of 17 fatal H7N9 cases in Shanghai in 2013, analyzed clinical variables and described their clinical and epidemiologic characteristics. The median age was 73 years, and 82.4% had underlying medical conditions. The most frequent symptoms were fever (100%), followed by productive cough (47.1%) and dry cough (35.5%). Thirteen (76.5%) patients had dyspnea or respiratory distress, five (29.4%) had shock, and four (23.5%) had acute kidney injury. Seventeen (100.0%) patients had lymphopenia. Involvement of both lungs was found by chest radiography in 14 (82.4%) patients at presentation. Fifteen (88.2%) patients were hospitalized. The median times from illness onset to hospitalization and to diagnosis confirmation were both six days. Eleven (64.7%) patients were admitted to the intensive care unit. Sixteen (94.1%) patients were treated with oseltamivir. The median time from illness onset to oseltamivir treatment was six days. Among six patients for whom the duration of viral shedding was available, the median duration of viral shedding after oseltamivir treatment was 17 days. The median time from illness onset to death was 11 days. Refractory hypoxemia accounted for most deaths. The clinical and epidemiologic characteristics in the Shanghai fatal series of patients do not differ from other reports of H7N9 patients in China. This investigation reflects a delay in the diagnosis and antiviral treatment of H7N9 patients in the early stage of the epidemic in Shanghai. Late antiviral treatment and a long duration of viral shedding may be associated with a fatal outcome in these patients.

Graphene-SnO2 nanocomposites decorated with quantum tunneling junctions: preparation strategies, microstructures and formation mechanism.

Tin dioxide (SnO2) and graphene are versatile materials that are vitally important for creating new functional and smart materials. A facile, simple and efficient ultrasonic-assisted hydrothermal synthesis approach has been developed to prepare graphene-SnO2 nanocomposites (GSNCs), including three samples with graphene/Sn weight ratios = 1 : 2 (GSNC-2), 1 : 1 (GSNC-1), and graphene oxide/Sn weight ratio = 1 : 1 (GOSNC-1). Low-magnification electron microscopy analysis indicated that graphene was exfoliated and adorned with SnO2 nanoparticles, which were dispersed uniformly on both the sides of the graphene nanosheets. High-magnification electron microscopy analysis confirmed that the graphene-SnO2 nanocomposites presented network tunneling frameworks, which were decorated with the SnO2 quantum tunneling junctions. The size distribution of SnO2 nanoparticles was estimated to range from 3 to 5.5 nm. Comparing GSNC-2, GSNC-1, and GOSNC-1, GOSNC-1 was found to exhibit a significantly better the homogeneous distribution and a considerably smaller size distribution of SnO2 nanoparticles, which indicated that it was better to use graphene oxide as a supporting material and SnCl4·5H2O as a precursor to synthesize hybrid graphene-SnO2 nanocomposites. Experimental results suggest that the graphene-SnO2 nanocomposites with interesting SnO2 quantum tunneling junctions may be a promising material to facilitate the improvement of the future design of micro/nanodevices.

Characterization of the triplet state of tanshinone IIA and its reactivity by laser flash photolysis.

Tanshinone IIA (Tan IIA) has the properties of cardiovascular protection, anti-inflammation, antioxidation and anticancer. Its light-induced instability has drawn our interests in its photochemistry. Therefore, laser flash photolysis herein was used to investigate the transient photochemistry of Tan IIA. Our results show that direct photoexcitation by 355 nm laser pulses or photosensitization by energy transfer can lead to the formation of the triplet state of Tan IIA ((3)Tan IIA*). The triplet absorption spectrum and molar absorption coefficient, and ISC quantum yield were determined. Self-quenching of (3)Tan IIA* by its ground state was identified as an autooxidation reaction. (3)Tan IIA* was proved to react quickly with N, N-dimethylaniline, tert-butylhydroquinone and propyl gallate via electron transfer with the diffusion-controlled rate constants. One of the products with maximum absorption around 390 nm was assigned to the radical anion of Tan IIA. Our results indicate that (3)Tan IIA* is a reactive transient species and can be generated by photosensitization or direct photoexcitation. According to our results, the possible role of Tan IIA as a photosensitizer to induce potential phototoxicity via Type-II pathway in the presence of O2 can be predicted.

Interaction of retinoic acid radical cation with lysozyme and antioxidants: laser flash photolysis study in microemulsion.

All-trans retinoic acid (ATRA) plays essential roles in the normal biological processes and the treatment of cancer and skin diseases. Considering its photosensitive property, many studies have been focused on the photochemistry of ATRA. In this study, we investigated the transient phenomena in the laser flash photolysis (LFP) of ATRA in microemulsion to further understand the photochemistry of ATRA. Results show that 355 nm LFP of ATRA in both acidic and alkaline conditions leads to the generation of retinoic acid cation radicals (ATRA(•+)) via biphotonic processes. The employment of microemulsion system allows us to investigate the reaction of hydrophobic ATRA(•+) with molecules of different polarity. Therefore, we studied the reaction activity of ATRA(•+) to many hydrophobic and hydrophilic molecules. Results show that ATRA(•+) can efficiently interact with lysozyme, tyrosine, tryptophan and many antioxidants, such as curcumin (Cur), vitamin C (VC) and gallic acid (GA). The apparent rate constants of these reactions were measured and compared. These findings suggest that ATRA(•+) is a reactive transient product which may pose damage to lysozyme, and antioxidants, such as Cur, VC and GA, may inactivate ATRA(•+) by efficient quenching reactions.

Synergetic effect of SLN-curcumin and LDH-5-Fu on SMMC-7721 liver cancer cell line.

Curcumin and 5-Fluorouracil (5-Fu) have been reported to have anticancer potentials and show certain synergetic effect on some cancer cell lines. However, the poor bioavailability and rapid metabolism limited their medical application. In this study, we encapsulated curcumin with solid lipid nanoparticles (SLN), 5-Fu with Layered double hydroxides (LDHs) separately and tested its properties and anticancer potentials. SLN-curcumin and LDH-5-Fu were determined to be 100 and 60 nm by Transmission Electron Microscopy detection, and the loading efficiency were 28%±2.5% and 16.7%±1.8%, individually. Furthermore, SLN-curcumin and LDH-5-Fu showed a significantly synergetic effect on SMMC-7721 cell stronger than plain drugs together, of which the Idrug loaded nano-carriers was only 0.315. FACS analysis revealed that the combination of SLN-curcumin and LDH-5-Fu induced 80.1% apoptosis in SMMC-7721 cells, which were 1.7-folds of the sum of the two plain drug loaded carriers. The results demonstrated the significant synergetic anticancer potentials of nano-encapsulated curcumin and 5-Fu, which could be further explored for the treatment of other carcinoma.