Metabolomic profiling of Saposhnikoviae Radix from Mongolia by LC–IT–TOF–MS/MS and multivariate statistical analysis

Journal of Natural Medicines - Saposhnikoviae Radix (SR) is a commonly used crude drug that is obtained from the root and rhizome of Saposhnikovia divaricata which is distributed throughout China,...     

Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin

Aims/Introduction

The aim of the present study was to evaluate the long‐term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase‐4 inhibitor, sitagliptin, in addition to diet and exercise therapies.

Materials and Methods

This was a multicenter, uncontrolled, dose‐titration study with a treatment period of 52 weeks. The primary end‐point was the change in glycated hemoglobin levels from baseline.

Results

The glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were −0.44 ± 0.28% and −0.50 ± 0.82%, respectively. The glycated hemoglobin‐lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of ‘major hypoglycemia’.

Conclusions

Combination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.     

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.A long-term goal in contemporary cancer nanomedicine has been to design and generate drug delivery systems that improve the narrow therapeutic window associated with conventional chemotherapeutics (1, 2). Conceptually, several nanotechnology-based entity candidates, including protocells (3), biosynthetic nanoparticles (NPs), viruses, and liposome-based nanoparticles, could be targeted for active delivery through a defined cell surface ligand receptor system and/or physically triggered for finely tuned cargo release (2, 4, 5).Numerous efforts have been made to functionalize NPs by combining them with antibodies, aptamers, peptides, vitamins, or carbohydrates (6–8), but the majority of studies involve untargeted nanoplatforms (4, 9). In practice, targeting NPs is far from trivial, and ongoing challenges include synthesis and purification, selection of an appropriate ligand receptor, and specific composition for NP conjugation. Even the conjugation reaction itself may alter the binding of the tumor-targeting moiety to its receptor through conformational changes, steric freedom restriction, or orientation distortion (10, 11). Unfortunately, the cost-to-benefit ratio of these modifications often elevate the complexity of the NP synthesis, complicating regulatory hurdles because of formulations that are heterogeneous or difficult to reproduce (10, 12, 13).To minimize such drawbacks, NPs can be functionalized via virus-based nanoplatforms as an alternative for targeted cargo delivery (14–16). In particular, filamentous bacteriophage (phage)—a prokaryotic virus—is an attractive candidate to develop a bionanomedicine for cancer therapeutics because phage particles are cost-effectively produced with biological uniformity, as well as being physically robust and stable under harsh conditions (17). Notably, phage-based nanoplatforms are biocompatible and nonpathogenic with eukaryotic organisms and are able to preserve the desired cell targeting and internalization (18). Moreover, phage particles are ideal for incorporating other NPs, which can be released after reaching the tumor site. An admixture of colloidal gold NP (AuNP) with phage particles spontaneously organizes into hydrogel network-like fractal structures (19, 20). These hydrogel networks offer convenient multifunctional integration within a single entity for tumor targeting, enhanced fluorescence and dark-field microscopy, near-infrared (NIR) photon-to-heat conversion, and surface-enhanced Raman scattering (SERS)-based detection (20, 21).In the present work, we developed a tumor targeting theranostic (meaning a combination of therapeutics and diagnostics) hydrogel-based nanoplatform that enables ligand-directed tumor targeting, multimodal imaging capability, and triggered therapeutic cargo release. Our data suggest that targeted hydrogel photothermal therapy represents a functional theranostic approach (fostering “see and treat, treat and see”) in the diagnosis and management of tumors.     

Successful laparoscopic extirpation of a large omental lipoblastoma in a child

Omental lipoblastoma is extremely rare among benign tumors. We herein report the case of a child who underwent laparoscopic extirpation of a large omental lipoblastoma. A 4‐year‐old girl was diagnosed with an intra‐abdominal solid tumor. Abdominal imaging revealed a fat density mass that was well encapsulated and measured 18 × 15 × 7.5 cm in size. Considering the MRI findings and movability of the tumor, we strongly suspected that the lesion was an omental lipoblastoma. We initially decided to perform laparoscopic exploration and, if possible, extirpation of the solid tumor sequentially. A total of five trocars were used, and the tumor was found to originate from the omentum. We successfully performed complete resection of the tumor laparoscopically. A histological examination revealed lipoblastoma. For large abdominal tumors in children, the laparoscopic approach is recommended as the first procedure when the tumor is preoperatively considered to be benign and resectable.