Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit

<p>Abstract</p> <p>Background</p> <p>Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH.</p> <p>Results</p> <p>Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 μm²) is significantly smaller than that in control group (462,128 ± 74,756 μm²), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 μm²) and SAH + vitamin C group (237,820 ± 21,703 μm²). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 μm², which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (<it>P </it>< 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (<it>P </it>> 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (<it>P </it>< 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Polymeric Systems Containing Supramolecular Coordination Complexes for Drug Delivery

Cancer has become a common disease that seriously endangers human health and life. Up to now, the essential treatment method has been drug therapy, and drug delivery plays an important role in cancer therapy. To improve the efficiency of drug therapy, researchers are committed to improving drug delivery methods to enhance drug pharmacokinetics and cancer accumulation. Supramolecular coordination complexes (SCCs) with well-defined shapes and sizes are formed through the coordination between diverse functional organic ligands and metal ions, and they have emerged as potential components in drug delivery and cancer therapy. In particular, micelles or vesicles with the required biocompatibility and stability are synthesized using SCC-containing polymeric systems to develop novel carriers for drug delivery that possess combined properties and extended system tunability. In this study, the research status of SCC-containing polymeric systems as drug carriers and adjuvants for cancer treatment is reviewed, and a special focus is given to their design and preparation

Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy

Polymeric Systems Containing Supramolecular Coordination Complexes for Drug Delivery

Cancer has become a common disease that seriously endangers human health and life. Up to now, the essential treatment method has been drug therapy, and drug delivery plays an important role in cancer therapy. To improve the efficiency of drug therapy, researchers are committed to improving drug delivery methods to enhance drug pharmacokinetics and cancer accumulation. Supramolecular coordination complexes (SCCs) with well-defined shapes and sizes are formed through the coordination between diverse functional organic ligands and metal ions, and they have emerged as potential components in drug delivery and cancer therapy. In particular, micelles or vesicles with the required biocompatibility and stability are synthesized using SCC-containing polymeric systems to develop novel carriers for drug delivery that possess combined properties and extended system tunability. In this study, the research status of SCC-containing polymeric systems as drug carriers and adjuvants for cancer treatment is reviewed, and a special focus is given to their design and preparation

Synthesis and optical properties of three novel functional polyurethanes bearing nonlinear optical chromophoric pendants with different pi electron conjugation bridge structure

High molecular weight functional polyurethanes bearing large pi electron conjugated chromophoric pendants with different conjugation bridge structure, poly(1a), poly(1b), and poly(1e), were synthesized and characterized by FTIR, H-1 NMR and UV-vis absorption spectra. Their optical properties were evaluated by optical limiting and nonlinear optical analyses. The results show that these polymers possess good optical limiting and large nonlinear optical properties, which are attributed to the long D-pi-A conjugated pi electron structure of the NLO-chromophoric segment. Poly(la) with C=C double bond as pi electron conjugation bridge shows better optical limiting property than poly(1b) and poly(1c) with C=N or N=N double bond as conjugation bridge structure under the same linear transmittance, while poly(le) with N=N double bond as pi electron conjugation bridge of the NLO-chromophoric segment is superior on nonlinear optical properties to poly(la) and poly(1b) with C=C and C=N double bonds as pi electron conjugation bridge structure, respectively. (c) 2006 Elsevier Ltd. All rights reserved

Experiment Study for Wrist-Wearable Electro-Tactile Display

Tactile sensation is a promising information display channel for human beings that involves supplementing or replacing degraded visual or auditory channels. In this paper, a wrist-wearable tactile rendering system based on electro-tactile stimulation is designed for information expression, where a square array with 8 × 8 spherical electrodes is used as the touch panel. To verify and improve this touch-based information display method, the optimal mode for stimulus signals was firstly investigated through comparison experiments, which show that sequential stimuli with consecutive-electrode-in-active mode have a better performance than those with single-electrode-in-active mode. Then, simple Chinese and English characters and 26 English characters’ recognition experiments were carried out and the proposed method was verified with an average recognition rate of 95% and 82%, respectively. This wrist-wearable tactile display system would be a new and promising medium for communication and could be of great value for visually impaired people

Architectures and Applications of BODIPY-Based Conjugated Polymers

Conjugated polymers generally contain conjugated backbone structures with benzene, heterocycle, double bond, or triple bond, so that they have properties similar to semiconductors and even conductors. Their energy band gap is very small and can be adjusted via chemical doping, allowing for excellent photoelectric properties. To obtain prominent conjugated materials, numerous well-designed polymer backbones have been reported, such as polyphenylenevinylene, polyphenylene acetylene, polycarbazole, and polyfluorene. 4,4&prime;-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based conjugated polymers have also been prepared owing to its conjugated structure and intriguing optical properties, including high absorption coefficients, excellent thermal/photochemical stability, and high quantum yield. Most importantly, the properties of BODIPYs can be easily tuned by chemical modification on the dipyrromethene core, which endows the conjugated polymers with multiple functionalities. In this paper, BODIPY-based conjugated polymers are reviewed, focusing on their structures and applications. The forms of BODIPY-based conjugated polymers include linear, coiled, and porous structures, and their structure&ndash;property relationship is explored. Also, typical applications in optoelectronic materials, sensors, gas/energy storage, biotherapy, and bioimaging are presented and discussed in detail. Finally, the review provides an insight into the challenges in the development of BODIPY-based conjugated polymers

Preparation and property of soluble azobenzene-containing substituted poly(1-alkyne)s optical limiting materials

Two novel poly(1-alkyne)s containing azobenzene nonlinear optical chromophoric group, poly(4-(4-[4-(n-dodecyloxy)phenylazophenyl]carbonyl)oxy-1-butyne) (P1) and poly(11-(4-[4-(n-dodecyloxy)phenylazophenyl]carbonyl)oxy-1-undecyne) (P2), were synthesized by [Rh(nbd)Cl](2)-Et3N catalysts and characterized by FTIR, H-1 NMR, GPC and UV-vis techniques. Their optical limiting and nonlinear optical properties were investigated using 8 ns pulse at 532 nm. The results show that these soluble functional poly(1-alkyne)s possess good optical limiting properties and large nonlinear optical properties. (c) 2006 Elsevier Ltd. All rights reserved