Fluid management in children with severe dengue: a narrative review.

Dengue is a mosquito-borne arboviral infection of increasing public health importance. Globally, children account for a significant proportion of infections. No pathogen-specific treatment currently exists, and the current approach to reducing disease burden is focused on preventative strategies such as vector control, epidemiological interventions, and vaccination in selected populations. Once infected, the mainstay of treatment is supportive, of which appropriate fluid management is a cornerstone. The timely provision of fluid boluses has historically been central to the management of septic shock. However, in patients with dengue shock, particular emphasis is placed on judicious fluid administration. Certain colloids such as hydroxyethyl starches and dextran, despite no longer being used routinely in intensive care units due to concerns of acute kidney injury and impairment of coagulation, are still commonly used in dengue shock syndrome. Current guidelines recommend initial crystalloid therapy, with consideration of colloids for severe or recalcitrant shock in patients with dengue. In this review, we discuss the pathophysiology of septic shock, and consider whether any differences in dengue exist that may warrant a separate approach to fluid therapy. We critically review the available evidence for fluid management in dengue, including the role of colloids. In dengue, there is increasing recognition of the importance of tailoring fluid therapy to phases of disease, with attention to the need for fluid "deresuscitation" once the critical phase of vascular leak passes.

Phenylboronic ester-modified anionic micelles for ROS-stimuli response in HeLa cell.

Smart polymers as ideal drug nanocarriers have attracted much attention due to the effective drug delivery, internalization and release once triggered by intracellular stimuli, as well as reduced cytotoxicity. We here reported the anionic micelle consisting of copolymer (PEG-b-PAsp) and a PBE (Phenylboronic Ester) group grafted, which can achieve fast response to intracellular ROS and enhanced anti-tumor activity. With this, PEG-b-PAsp-g-PBE/DOX system showed better tumor growth inhibition when studied on HeLa cell lines with high level of intracellular ROS and its subcutaneous tumor models. Additionally, the administration of PEG-b-PAsp-g-PBE/DOX did cause significantly lower systemic toxicity in comparison with free DOX. Hence, PEG-b-PAsp-g-PBE could be a highly efficient and safe nanocarrier to improve the efficacy of chemotherapeutic.

Peptide-mediated cationic micelles drug-delivery system applied on a VEGFR3-overexpressed tumor.

Copolymers as a kind of drug delivery carrier always lack targeting efficiency. So a peptide conjugated to a drug delivery system has attracted much attention for tumor-targeted nanomedicine. Thus, we here report a conjugation compound consisting of a copolymer (PEG-b-PLL) and a peptide (Cys-Ile-Gln-Pro-Phe-Tyr-Pro, CP7). For receptor-mediated endocytosis by this peptide, the CP7-PEG-b-PLL conjugation significantly enhanced the chemotherapeutic efficacy as a potent nanocarrier compared with free DOX. The CP7-PEG-b-PLL exhibited excellent pharmacokinetic behavior via a radioactive iodine-131 (I) tracing method. With this, the CP7-PEG-b-PLL/DOX system showed better tumor growth inhibition when studied on A549 cell lines and subcutaneous tumor models, but with less toxicity than free DOX. All these results suggest that the CP7-modified drug cationic micelles could represent a novel platform for successful drug delivery toward VEGFR3-overexpressed tumors.

De Novo Computational Design for Development of a Peptide Ligand Oriented to VEGFR-3 with High Affinity and Long Circulation.

The overexpression of VEGFR-3 is correlated with a worse prognosis in lung cancer and has been regarded as a rational target for specific drug delivery. Here, VEGFR-3 homing peptide library was efficiently established by computational design. Strong fluorescent signals of selected peptides were observed in A549 cells, but much weaker in other cells. The positive immunostaining overlapped with VEGFR-3 confirmed high affinity and selectivity of one novel peptide (CP-7). In addition, cell uptake of FITC-CP-7 peptide was significantly blocked by coinjection of excess CP-7 peptide. After labeled with 131I, the profile of pharmacology and biodistribution could be traced in vivo. The 131I-radiolabeled CP-7 peptide conjugates were >85% stable in serum over 4 h and exhibited a specific uptake of 18.04 ± 2.04% ID/g at 0.5 h after injection to high VEGFR-3 expressing A549 tumor mice. More importantly, lower uptake concentration in heart (1.06 ± 0.15% ID/g) after 2 h demonstrated the safety of peptide in vivo. The high uptake in the kidneys revealed that renal clearance was the main route of 131I-CP-7 peptide elimination from the body. Lower accumulation of 131I-CP-7 peptide in VEGFR-3 negative HeLa tumor mice further indicated that CP-7 peptide exhibited a higher tumor-homing efficiency. These studies provided a straightforward analytical access to design and screen bioactive peptide based on protein structure and revealed that CP-7 peptide represented a promising homing peptide of VEGFR-3-positive cancer in vitro and in vivo which could be used as a novel target molecule to achieve efficient drug delivery.

An Integrative Folate-Based Metal Complex Nanotube as a Potent Antitumor Nanomedicine as Well as an Efficient Tumor-Targeted Drug Carrier.

Metal-organic complexes (MOCs) are emerging developing functional materials, the different categories of metal ions and organic biomolecules provide great possibilities for the morphologies, sizes, and properties of the products. Enlightened by the previous works of folate-nickel nanotubes (FA-Ni NTs), herein, a series of metal ions are tested to coordinate with folate (FA) by the solvothermal method, among which the folate-cobalt(II) complex is formed to be a scaffold for the nanotube with the length of 150-500 nm and inner diameter of 6-11 nm, while the other metal ions fail. In vitro experiments reveal that folate-cobalt nanotubes (FA-Co NTs) have excellent antitumor activity toward tumor cells with high expression levels of folate receptor (FR), whereas they show extremely low toxicity to normal cells. Furthermore, these kinds of NTs show better antitumor ability when the anticancer drug doxorubicin is encapsulated through cell surface receptor-mediated endocytosis. Moreover, we study the fundamental pharmacokinetic profiles and biodistribution of FA-Co NTs on mice and also prove its targeting capability to tumor tissues on tumor-bearing mice using the radioactive iodine-131 (131I) tracing method. FA-Co NTs can also markedly inhibit the growth of tumor with minimal side effects when administered individually in vivo. These findings will expand the research on FA based metal complex nanomaterials as a kind of potential antitumor nanomedicine as well as a targeted drug carrier.