Network pharmacology-based investigation and experimental validation of the therapeutic potential and molecular mechanism of Danshen Chuanxiongqin injection in acute pancreatitis.

BACKGROUND: Danshen Chuanxiong Injection (DCI) has demonstrated significant clinical efficacy in the treatment of acute pancreatitis (AP); however, the precise molecular mechanisms underlying its therapeutic effects remain incompletely understood. OBJECTIVE: In this study, we employed network pharmacology analysis to comprehensively investigate the active components, potential targets, and signaling pathways involved in DCI-mediated treatment of AP. METHODS: We utilized the mouse pancreatic acinar cell line 266-6 to establish an cholecystokinin (CCK)-induced AP cell injury model and evaluated cell viability using the Cell counting kit-8 assay. Western blotting and quantitative PCR were employed to determine the expression levels of key target proteins and genes. RESULTS: Network pharmacology analysis identified a total of 144 active components and 430 potential targets within DCI. By integrating data from public databases, we identified 762 AP-related genes. Among these, we identified 93 potential targets that may be involved in the therapeutic effects of DCI for AP. These targets were significantly enriched in biological processes such as oxidative stress, regulation of cytokine production, leukocyte migration, and the TNF signaling pathway. Molecular docking studies revealed a high binding affinity between the active components and the key targets AKT1 and NFKBA, indicative of potential interaction. Additionally, CCK-induced acinar cell injury led to upregulation of AKT1, NFKBA, and P53 proteins, as well as TNF, IL6, and MMP9 genes. Conversely, treatment with DCI dose-dependently attenuated CCK-induced acinar cell injury and restored the expression levels of the aforementioned proteins and genes. CONCLUSION: Overall, this study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of DCI in the treatment of AP. Our findings confirm the protective effect of DCI against CCK-induced acinar cell injury and its regulation of key targets.

Evaluation of 2-deoxy-2-[18F]fluoro glucaric acid (FGA) as a potential PET tracer for tumor necrosis.

In this study, [18F]FGA was obtained by a one-step oxidation of [18F]FDG using sodium hypochlorite. The conversion from [18F]FDG to [18F]FGA was confirmed by HPLC to be over 95% using the optimal condition. A549-luciferase NSCLC xenografted mice was used for in vivo PET imaging. Prior to either saline or cisplatin treatment, there was no significant difference on tumor uptake of [18F]FGA in all mice, with an average uptake of (0.21 ± 0.16) %ID/g. After treatment, tumor uptake of [18F]FGA was not changed significantly for saline-treated mice, whereas the tumor uptake of [18F]FGA drastically increased for cisplatin-treated mice, with an average uptake of (1.63 ± 0.16) %ID/g. The ratio of tumor uptake between cisplatin-treated vs. saline-treated mice was 7.8 ± 0.2 within one week of treatment. PET imaging results were consistent with ex vivo biodistribution data. BLI showed significant light intensity suppression after treatment, indicating necrosis. Our data indicate that [18F]FGA uptake was related to tumor necrosis. [18F]FGA PET/CT imaging might be a useful tool to monitor treatment response to chemotherapy by imaging tumor necrosis.

A meta-analysis of the association between vitamin D supplementation and the risk of acute respiratory tract infection in the healthy pediatric group.

No previous meta-analysis had explored the association between vitamin D supplementation in healthy pediatrics and the risk of acute respiratory tract infections (ARTIs). Thus, we meta-analyzed the current evidence in this regard to provide sufficient knowledge about this risk-benefit ratio for vitamin D supplementation in this specific age group. We searched seven databases for randomized controlled trials (RCTs) that investigated the effect of vitamin D supplementation and ARTIs risk on a healthy pediatric population (0-18 years old). Meta-analysis was performed through R software. We included eight RCTs after the screening of 326 records according to our eligibility criteria. There were comparable infection rates between Vitamin D and placebo groups (OR = 0.98, 95% CI = 0.90-1.08, P-value = 0.62), with no significant heterogeneity among the included studies (I2 = 32%; P-value = 0.22). Moreover, there was no significant difference between the two vitamin D regimens (OR = 0.85, 95% CI = 0.64-1.12, P-value = 0.32), with no considerable heterogeneity among the included studies (I2 = 37%; P-value = 0.21). However, there was a significant reduction in Influenza A rates in the high-dose vitamin D group compared to the low dose one (OR = 0.39, 95% CI = 0.26-0.59, P-value < 0.001), with no heterogeneity among the included studies (I2 = 0%; P-value = 0.72). Only two studies of 8,972 patients reported different side effects, with overall acceptable safety profile. Regardless of the dosing regimen used or the type of infection, in the healthy pediatric group, there is no evident benefit of using vitamin D to prevent or reduce the ARTI rates.

Production, identification, in silico analysis, and cytoprotection on H2O2-induced HUVECs of novel angiotensin-I-converting enzyme inhibitory peptides from Skipjack tuna roes.

Background: Exceeding 50% tuna catches are regarded as byproducts in the production of cans. Given the high amount of tuna byproducts and their environmental effects induced by disposal and elimination, the valorization of nutritional ingredients from these by-products receives increasing attention. Objective: This study was to identify the angiotensin-I-converting enzyme (ACE) inhibitory (ACEi) peptides from roe hydrolysate of Skipjack tuna (Katsuwonus pelamis) and evaluate their protection functions on H2O2-induced human umbilical vein endothelial cells (HUVECs). Methods: Protein hydrolysate of tuna roes with high ACEi activity was prepared using flavourzyme, and ACEi peptides were isolated from the roe hydrolysate using ultrafiltration and chromatography methods and identified by ESI/MS and Procise Protein/Peptide Sequencer for the N-terminal amino acid sequence. The activity and mechanism of action of isolated ACEi peptides were investigated through molecular docking and cellular experiments. Results: Four ACEi peptides were identified as WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12), respectively. The affinity of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) with ACE was -8.590, -9.703, -9.325, and -8.036 kcal/mol, respectively. The molecular docking experiment elucidated that the significant ACEi ability of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) was mostly owed to their tight bond with ACE's active sites/pockets via hydrophobic interaction, electrostatic force and hydrogen bonding. Additionally, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could dramatically elevate the Nitric Oxide (NO) production and bring down endothelin-1 (ET-1) secretion in HUVECs, but also abolish the opposite impact of norepinephrine (0.5 µM) on the production of NO and ET-1. Moreover, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could lower the oxidative damage and apoptosis rate of H2O2-induced HUVECs, and the mechanism indicated that they could increase the content of NO and activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to decrease the generation of reactive oxygen species (ROS) and malondialdehyde (MDA). Conclusion: WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) are beneficial ingredients for healthy products ameliorating hypertension and cardiovascular diseases.

Consumption of fish oil high-fat diet induces murine hair loss via epidermal fatty acid binding protein in skin macrophages.

Fats are essential in healthy diets, but how dietary fats affect immune cell function and overall health is not well understood. Mimicking human high-fat diets (HFDs), which are rich in different fatty acid (FA) components, we fed mice various HFDs from different fat sources, including fish oil and cocoa butter. Mice consuming the fish oil HFD exhibit a hair-loss phenotype. Further studies show that omega-3 (n-3) FAs in fish oil promote atypical infiltration of CD207- (langerin-) myeloid macrophages in skin dermis, which induce hair loss through elevated TNF-α signaling. Mechanistically, epidermal fatty acid binding protein (E-FABP) is demonstrated to play an essential role in inducing TNF-α-mediated hair loss by activating the n-3 FA/ROS/IL-36 signaling pathway in dermal resident macrophages. Absence of E-FABP abrogates fish oil HFD-induced murine hair loss. Altogether, these findings support a role for E-FABP as a lipid sensor mediating n-3 FA-regulated macrophage function and skin health.

Specific deletion of CDC42 in pancreatic ß cells attenuates glucose-induced insulin expression and secretion in mice.

Insulin is a key hormone for maintaining glucose homeostasis in organisms. In general, deficiency of insulin synthesis and secretion results in type I diabetes, whereas insulin resistance leads to type 2 diabetes. Cell division cycle 42 (CDC42), a member of Rho GTPases family, has been shown as an essential regulator in the second phase of glucose-induced insulin secretion in pancreatic islets ß cells in vitro. However, the effect of CDC42 on insulin expression has not been explored. Here we reported that the glucose-induced insulin expression and secretion were significantly inhibited in mice lacking CDC42 gene in pancreatic ß cells (Rip-CDC42cKO) in vivo and in vitro. Deletion of CDC42 gene in pancreatic ß cells did not affect survival or reproduction in mice. However, the Rip-CDC42cKO mice showed the systemic glucose intolerance and the decrease of glucose-induced insulin secretion without apparent alterations of peripheral tissues insulin sensitivity and the morphology of islets. Furthermore, we demonstrated that deletion of CDC42 gene in pancreatic ß cells significantly attenuated the insulin expression through inhibiting the ERK1/2-NeuroD1 signaling pathway. Taken together, our study presents novel evidence that CDC42 is an important modulator in glucose-induced insulin expression as well as insulin secretion in pancreatic ß cells.

Recruitment of monocytes and epigenetic silencing of intratumoral CYP7B1 primarily contribute to the accumulation of 27-hydroxycholesterol in breast cancer.

Previous studies showed that intratumoral 27-Hydroxycholesterol (27-HC), a metabolite of cholesterol, promotes growth, invasion and migration of breast cancer cells and that tumor-associated macrophages (TAMs) in breast cancers are closely related to tumor growth and metastatic progression. However, the relationship between 27-HC and TAMs in breast cancer remains unclear. In the present study, we observed that CYP27A1, the 27-HC synthesizing enzyme, was expressed in a much higher level in THP1 monocytes and THP1-derived macrophages than in breast cancer cells, and the promoter of CYP7B1, the degrading enzyme for 27-HC, was highly methylated in breast tumor cells. In addition, THP-1 monocytes and murine bone marrow cells were differentiated toward M2 type macrophages after being co-cultured with breast cancer cells or being exposed to exosomes derived from breast cancer cells. M2 type macrophages produced higher amounts of 27-HC than M0 and M1 type macrophages. 27-HC not only stimulated ER+ cancer cell proliferation as reported, but also promoted the recruitment of CCR2- and CCR5-expressing monocytes by inducing macrophages to express multiple chemokines including CCL2, CCL3 and CCL4. Taken together, our data demonstrate that the hypermethylation of CYP7B1 and recruitment of monocytes likely contribute to the accumulation of 27-Hydroxycholesterol in breast cancer and that the interaction of 27-HC with macrophages further promote the development of breast cancer.

Carnosine Supplementation Enhances Post Ischemic Hind Limb Revascularization.

High (millimolar) concentrations of the histidine containing dipeptide - carnosine (ß-alanine-L-histidine) are present in the skeletal muscle. The dipeptide has been shown to buffer intracellular pH, chelate transition metals, and scavenge lipid peroxidation products; however, its role in protecting against tissue injury remains unclear. In this study, we tested the hypothesis that carnosine protects against post ischemia by augmenting HIF-1α angiogenic signaling by Fe2+ chelation. We found that wild type (WT) C57BL/6 mice, subjected to hind limb ischemia (HLI) and supplemented with carnosine (1g/L) in drinking water, had improved blood flow recovery and limb function, enhanced revascularization and regeneration of myocytes compared with HLI mice placed on water alone. Carnosine supplementation enhanced the bioavailability of carnosine in the ischemic limb, which was accompanied by increased expression of proton-coupled oligopeptide transporters. Consistent with our hypothesis, carnosine supplementation augmented HIF-1α and VEGF expression in the ischemic limb and the mobilization of proangiogenic Flk-1+/Sca-1+ cells into circulation. Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions. Similarly pretreatment of WT C57/Bl6 mice with carnosine showed enhanced blood flow in the ischemic limb following HLI surgery. In contrast, pretreatment of hypoxic C2C12 cells with methylcarcinine, a carnosine analog, lacking Fe2+ chelating capacity, had no effect on HIF-1α levels and VEGF release. Collectively, these data suggest that carnosine promotes post ischemic revascularization via augmentation of pro-angiogenic HIF-1α/VEGF signaling, possibly by Fe2+ chelation.

Validation of 2-18F-Fluorodeoxysorbitol as a Potential Radiopharmaceutical for Imaging Bacterial Infection in the Lung.

2-18F-fluorodeoxysorbitol (18F-FDS) has been shown to be a promising agent with high selectivity and sensitivity in imaging bacterial infection. The objective of our study was to validate 18F-FDS as a potential radiopharmaceutical for imaging bacterial infection longitudinally in the lung. Methods: Albino C57 female mice were intratracheally inoculated with either live or dead Klebsiella pneumoniae to induce either lung infection or lung inflammation. One group of mice was imaged to monitor disease progression. PET/CT was performed on days 0, 1, 2, and 3 after inoculation using either 18F-FDS or 18F-FDG (n = 12 for each tracer). The other group was first screened by bioluminescent imaging (BLI) to select only mice with visible infection (region of interest > 108 ph/s) for PET/CT imaging with 18F-FDS (n = 12). For the inflammation group, 5 mice each were imaged with PET/CT using either 18F-FDS or 18F-FDG from days 1 to 4 after inoculation. Results: For studies of disease progression, BLI showed noticeable lung infection on day 2 after inoculation and significantly greater infection on day 3. Baseline imaging before inoculation showed no focal areas of lung consolidation on CT and low uptake in the lung for both PET radiotracers. On day 2, an area of lung consolidation was identified on CT, with a corresponding 2.5-fold increase over baseline for both PET radiotracers. On day 3, widespread areas of patchy lung consolidation were found on CT, with a drastic increase in uptake for both 18F-FDS and 18F-FDG (9.2 and 3.9). PET and BLI studies showed a marginal correlation between 18F-FDG uptake and colony-forming units (r = 0.63) but a much better correlation for 18F-FDS (r = 0.85). The uptake ratio of infected lung over inflamed lung was 8.5 and 1.7 for 18F-FDS and 18F-FDG on day 3. Conclusion: Uptake of both 18F-FDS and 18F-FDG in infected lung could be used to track the degree of bacterial infection measured by BLI, with a minimum detection limit of 107 bacteria. 18F-FDS, however, is more specific than 18F-FDG in differentiating K. pneumoniae lung infection from lung inflammation.

Assessment of radiopharmaceutical retention for vascular access ports using positron emission tomography imaging.

PURPOSE: The purpose of this study was to resolve the issue of whether various generations of CR Bard peripheral vascular access ports and catheters are prone to retain PET radiopharmaceuticals. The study evaluates the residual radioactivity remaining following injection for two PET radiopharmaceuticals currently used extensively in the clinic, FDG and Na18 F. METHODS: FDG was purchased from a local cyclotron facility and Na18 F was prepared in-house. Three generations of currently marketed vascular access ports were tested. A total of five (n = 5) of each model was tested. Radiopharmaceutical of 2-3 mCi of each was injected into each port and flushed with 10, 30, 60, and 120 ml of saline. MicroPET scans were performed after each flush to detect the residual radioactivity on each port. A dose calibrator was used to detect the retention of radioactivity after each flush. RESULTS: Radioactivity retention for all vascular port models measured by microPET imaging was similar for both FDG and Na18 F, with less than 1% residual activity following a 10 ml saline flush. Based on the microPET images, all the subsequent flushes of 30, 60, and 120 ml were also considered. Dose calibrator activity measurements validated microPET measurements as negligible for all the ports, even with the first 10 ml flush. CONCLUSIONS: MicroPET imaging was more sensitive than the dose calibrator in determining the radioactivity retention of the vascular access ports from CR Bard. These ports may be used for the injection of FDG and Na18 F to track glucose metabolism and bone uptake with PET imaging. It is recommended to apply at least a 10 ml flush after radiopharmaceutical administration, to reduce residual activity to baseline levels.

Expression profiling of TRIM protein family in THP1-derived macrophages following TLR stimulation.

Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup. Besides TRIM21, TRIM22 and TRIM38 were shown to be upregulated by TLR3 and TLR4 ligands as previous reported, we identified a novel group of TRIM genes (TRIM14, 15, 31, 34, 43, 48, 49, 51 and 61) that were significantly up-regulated by TLR3 and TLR4 ligands. In contrast, the expression of TRIM59 was down-regulated by TLR3 and TLR4 ligands in both human and mouse macrophages. The alternations of the TRIM proteins were confirmed by Western blot. Finally, overexpression of TRIM59 significantly suppressed LPS-induced macrophage activation, whereas siRNA-mediated knockdown of TRIM59 enhanced LPS-induced macrophage activation. Taken together, the study provided an insight into the TLR ligands-induced expressions of TRIM family in macrophages.

In Vitro PET Imaging of a Miniature Ventricular Assist Device.

UNLABELLED: Interactions between the life-sustaining ventricular assist devices and diagnostic therapies must be carefully considered to decrease the risk of inaccurate diagnostic imaging or pump failure. METHODS: The MVAD(®) pump, currently under investigational use, was tested for interaction with radiotracers in an in vitro flow-loop study. The radiotracers (18)F-sodium fluoride and (18)F-FDG were injected into a closed loop to determine the feasibility of direct imaging of the MVAD(®) pump in a PET scanner. RESULTS: No real-time changes were observed in pump operation, and there were no statistical differences in pump parameters (power consumption, speed, and estimated flow rate) between the baseline and circulation conditions. In addition, no effect was observed on any external components, including the permissive-action-link controller and the batteries powering the device. Imaging of the internal pump components was possible, with obscuration observed only in the portion of the pump where the spinning impeller is located. Retention of radiotracer in the pump components after circulation was minimal (<1%). CONCLUSION: PET imaging is an attractive diagnostic tool for patients with a ventricular assist device and may have additional utility outside its current use, detection of infection.

Systemically delivered adipose stromal vascular fraction cells disseminate to peripheral artery walls and reduce vasomotor tone through a CD11b+ cell-dependent mechanism.

Vasoactivity, an important aspect of tissue healing, is often compromised in disease and tissue injury. Dysfunction in the smaller vasoactive arteries is most impactful, given the role of these vessels in controlling downstream tissue perfusion. The adipose stromal vascular fraction (SVF) is a mix of homeostatic cells shown to promote tissue healing. Our objective was to test the hypothesis that autologous SVF cells therapeutically modulate peripheral artery vasoactivity in syngeneic mouse models of small artery function. Analysis of vasoactivity of saphenous arteries isolated from normal mice 1 week after intravenous injection of freshly isolated SVF cells revealed that pressure-dependent artery vasomotor tone was decreased by the SVF cell isolate, but not one depleted of CD11b(+) cells. Scavenging hydrogen peroxide in the vessel wall abrogated the artery relaxation promoted by the SVF cell isolate. Consistent with a CD11b(+) cell being the relevant cell type, SVF-derived F4/80-positive macrophages were present within the adventitia of the artery wall coincident with vasorelaxation. In a model of artery inflammation mimicking a common disease condition inducing vasoactive dysfunction, the SVF cells potentiated relaxation of saphenous arteries without structurally remodeling the artery via a CD11b(+) cell-dependent manner. Our findings demonstrate that freshly isolated, adipose SVF cells promote vasomotor relaxation in vasoactive arteries via a hydrogen peroxide-dependent mechanism that required CD11b(+) cells (most likely macrophages). Given the significant impact of small artery dysfunction in disease, we predict that the intravenous delivery of this therapeutic cell preparation would significantly improve tissue perfusion, particularly in diseases with diffuse vascular involvement.

The reverse Warburg effect and 18F-FDG uptake in non-small cell lung cancer A549 in mice: a pilot study.

UNLABELLED: The purpose of this study was to observe the effect of fasting and feeding on (18)F-FDG uptake in a mouse model of human non-small cell lung cancer. METHODS: In in vivo studies, (18)F-FDG small-animal PET scans were acquired in 5 mice bearing non-small cell lung cancer A549 xenografts on each flank with continuous feeding and after overnight fasting to observe the changes in intratumoral distribution of (18)F-FDG and tumor (18)F-FDG standardized uptake value (SUV). In ex vivo studies, intratumoral spatial (18)F-FDG distribution assessed by autoradiography was compared with the tumor microenvironment (including hypoxia by pimonidazole and stroma by hematoxylin and eosin stain). Five overnight-fasted mice and 5 fed mice with A549 tumors were observed. RESULTS: Small-animal PET scans were obtained in fed animals on day 1 and in the same animals after overnight fasting; the lapse was approximately 14 h. Blood glucose concentration after overnight fasting was not different from fed mice (P = 0.42), but body weight loss was significant after overnight fasting (P = 0.001). Intratumoral distribution of (18)F-FDG was highly heterogeneous in all tumors examined, and change in spatial intratumoral distribution of (18)F-FDG between 2 sets of PET images from the same mouse was remarkably different in all mice. Tumor (18)F-FDG mean SUV and maximum SUV were not significantly different between fed and fasted animals (all P > 0.05, n = 10). Only tumor mean SUV weakly correlated with blood glucose concentration (R(2) = 0.17, P = 0.03). In ex vivo studies, in fasted mice, there was spatial colocalization between high levels of (18)F-FDG uptake and pimonidazole-binding hypoxic cancer cells; in contrast, pimonidazole-negative normoxic cancer cells and noncancerous stroma were associated with low (18)F-FDG uptake. However, high (18)F-FDG uptake was frequently observed in noncancerous stroma of tumors but rarely in viable cancer cells of the tumors in fed animals. CONCLUSION: Host dietary status may play a key role in intratumoral distribution of (18)F-FDG. In the fed animals, (18)F-FDG accumulated predominantly in noncancerous stroma in the tumors, that is, reverse Warburg effect. In contrast, in fasted status, (18)F-FDG uptake was found in hypoxic cancer cells component (Pasteur effect). Our findings may provide a better understanding of competing cancer glucose metabolism hypotheses: the Warburg effect, reverse Warburg effect, and Pasteur effect.

Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery.

CONTEXT: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on. OBJECTIVE: Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers. METHODS: Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. (1)H nuclear magnetic resonance ((1)H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates. RESULTS AND DISCUSSION: PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ∼12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX. CONCLUSION: Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.

[Inhibition of MCF-7/ADR cells by DOX-loaded pluronic-attached PAMAM dendrimer conjugate].

Pluronic modified polyamidoamine (PAMAM) conjugate (PF127-PAMAM) was prepared and the inhibiting effect of MDR against MCF-7/ADR was investigated with doxorubicin (DOX) as model drug. 1H NMR and FTIR spectra showed that the conjugate was synthesized successfully. Element analysis accurately measured that 27.63% amino of per PAMAM was modified by pluronic (PAMAM : PF127, 1 : 35.37 mole ratio). PF127-PAMAM showed an increased size and a reduced zeta potential compared to PAMAM. PF127-PAMAM had lower hemolytic toxicity and cytotoxicity due to the reduced zeta potential and the protection of PF127. Each PF127-PAMAM molecular could load 19.58 DOX molecules, and the complex exhibited sustained and pH-sensitive release behavior. PF127-PAMAM/DOX exhibited weaker cytotoxicity than free DOX in MCF-7 cells; while the complex showed much stronger reverse effect of drug resistance in MCF-7/ADR cells, and resistance reversion index (RRI) was as high as 33.15.

Dendritic Ni-P-coated melamine foam for a lightweight, low-cost, and amphipathic three-dimensional current collector for binder-free electrodes.

A highly conductive 3D current collector that is dendritic, lightweight, and robust is synthesized for binder-free electrodes in lithium-ion batteries. It has excellent chemical/electrochemical stability in a wide voltage window (0-5 V) and robust mechanical behavior even after 600 cycles of compression. When active materials are grown in situ on the as-obtained current collector, the resulting cycling stability and rate capability far exceed those of conventional electrodes and other 3D current collectors.

Aptamer imaging with Cu-64 labeled AS1411: preliminary assessment in lung cancer.

INTRODUCTION: AS1411 is a 26-base guanine-rich oligonucleotide aptamer shown binding to surface nucleolin, a protein over-expressed in multiple cancer cells, thus AS1411 labeled with a PET isotope can be explored as a potential diagnostic imaging agent. Our objective was to perform preliminary biological characterization of (64)Cu-labeled AS1411 in vitro and in vivo. METHODS: Four chelators (DOTA, CB-TE2A, DOTA-Bn and NOTA-Bn) were selected to label AS1411 with Cu-64. 185kBq (5µCi) of each tracer was incubated in each well with H460 cells at 37°C for 1, 3, 6, 12, 24 and 48h, respectively (n=4). For microPET/CT imaging, 7.4MBq (200µCi) of AS1411 labeled with either (64)Cu-DOTA or (64)Cu-CB-TE2A was I.V. injected and multiple scans were obtained at 1, 3, 6 and 24h post injection. Afterward in vivo biodistribution studies were performed. RESULTS: Percent uptake of (64)Cu-DOTA-AS1411 and (64)Cu-CB-TE2A-AS1411 was significantly higher than that of (64)Cu-DOTA-Bn-AS1411 and (64)Cu-NOTA-Bn-AS1411. About 90% of uptake for (64)Cu-DOTA-AS1411 and (64)Cu-CB-TE2A-AS1411 was internalized into cells within 3h and the internalization process was completed before 24h. Both tracers demonstrated reasonable in vivo stability and high binding affinity to the cells. MicroPET imaging with (64)Cu-CB-TE2A-AS1411 showed clear tumor uptake at both legs from 1 to 24h post injection, whereas both tumors were undetectable for up to 24h with (64)Cu-DOTA-AS1411. In addition, (64)Cu-CB-TE2A-AS1411 had faster in vivo pharmacokinetics than (64)Cu-DOTA-AS1411 with lower liver uptake and higher tumor to background contrast. CONCLUSION: CB-TE2A is a preferred chelator with higher tumor-to-background ratio, lower liver uptake and faster clearance than DOTA. Aptamer imaging with (64)Cu-CB-TE2A-AS1411 may be feasible for detecting lung cancer, if an appropriate chelator can be identified and further validation can be performed with a known control oligonucleotide. It may also be used as a companion diagnostic imaging agent for AS1411 in the treatment of cancer.

Preparation, characterization and optimization of nanocellulose whiskers by simultaneously ultrasonic wave and microwave assisted.

Simultaneously ultrasonic wave and microwave assisted technique (SUMAT), as a method of process intensification, was first applied to the preparation of nanocellulose whiskers (NCWs) from filter paper by sulfuric acid hydrolysis. The effects of temperature, sulfuric acid concentration, and mass of raw material and time on the yield of NCWs were investigated by single-factor experiments, and the preparation conditions were optimized with response surface methodology. The obtained NCWs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and thermal gravimetry. The results showed NCWs were facilely prepared by using SUMAT. However, some harsh reaction conditions such as high temperature, strong acidity and long time treatment easily induced the reduction of the yield of NCWs. Under the optimal conditions, the yield and the crystallinity of NCWs with the crystal form of cellulose Iα is 85.75% and 80%, respectively.

Liquefaction of sawdust in 1-octanol using acidic ionic liquids as catalyst.

Acidic ionic liquids (AILs) as a novel catalyst in biomass liquefaction can accord with the demand of green chemistry and enhance the development of biomass thermal chemical conversion. A series of AILs containing HSO4- were synthesized by the imidazolium cation functionalization and applied to the Chinese fir sawdust liquefaction in 1-octanol in this paper. The experimental results showed that the liquefaction rate was gradually improved with the AILs acidity increasing, and reached 71.5% when 1-(4-sulfobutyl)-3-methylmidazolium hydrosulfate was used as catalyst with the 6:1 mass ratio of 1-octanol to sawdust at 423K after 60 min. Lignin, hemicellulose and cellulose were orderly desquamated, and then depolymerized and liquefied with the catalyst acidity increasing in the sawdust liquefaction process. The light oil was mainly composed of the octyl ether and the octyl ester compounds, suggesting that the solvent may play an important role in producing the high octane rating biofuel.