We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 µg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t_1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy.

Aims/Introduction: Studies have been carried out to evaluate the correlation between TCF7L2 genetic polymorphisms and gestational diabetes mellitus (GDM) risk. However, the conclusions from these studies are incomplete, because partial single nucleotide polymorphisms (SNPs) were analyzed. We carried out a meta‐analysis aimed to systematically evaluate TCF7L2 gene polymorphisms and GDM susceptibility in all population and racial/ethnic subgroups to afford a foundation for future research.Materials and Methods: Published studies censoring TCF7L2 variants and GDM risk were captured from the EMBASE, PubMed, CNKI and Wanfang databases. The meta‐analysis was processed using software of RevMan 5.2 and Stata13. The relationship between TCF7L2 polymorphism and GDM occurrence was evaluated by pooled odds ratios. Stratified analysis based on race/ethnicity was also carried out. The allele‐specific odds ratios and 95% confidence intervals were counted, and based on homogeneity evaluated using the I²‐test, fixed‐ or random‐effects pooled measures were selected.Results: A total of 22 studies were covered, capturing eight TCF7L2 SNPs and involving 5,573 cases and 13,266 controls. Six of eight SNPs showed significant relationships with GDM occurrence, of which the SNPs rs7903146, rs12255372 and rs7901695 were the most powerful. Stratified analysis by race/ethnicity showed discrepant results in these three SNPs. In Caucasians and other races, all these SNPs were found to have a significant association with GDM risk, but in Asians, only SNP rs7903146 showed a significant association.Conclusions: Six of eight SNPs were found to have significant associations between TCF7L2 variants and GDM risk in the overall population, with the most powerful in SNPs being rs7903146, rs12255372 and rs7901695, but the contribution of these SNPs to GDM risk were variable among different racial/ethnic groups.

Temozolomide (TMZ) is a widely used chemotherapeutic agent for glioblastoma multiforme (GBM). However, chemoresistance to TMZ is still a major obstacle for GBM patients. An abundance of candidates has been reported to improve the chemotherapeutic sensitization of TMZ. In the present study, it was demonstrated that momelotinib (MTB) enhanced the sensitivity of glioma cells to TMZ in vitro, as evidenced by a noticeable decrease in cell growth and a significant increase in apoptosis and autophagy following treatment with the combination of TMZ and MTB compared to TMZ alone. Mechanistically, MTB and TMZ combination treatment reduced U251 cell growth by activating both apoptosis and autophagy pathways. MTB potentiated TMZ to inhibit the phosphorylation of JAK2 and STAT3 in U251 cells, resulting in the inactivation of JAK2/STAT3 signaling pathways. Moreover, we investigated the effect of MTB in xenograft tumor model mice. MTB and TMZ combination reduced tumor weight, decreased the expression of Ki-67, P62, p-STAT3 and p-JAK2, while increased the ratio of LC3-II/I and the expression of caspase-3 and Beclin1 in vivo. Importantly, this combination was well tolerated, and caused significant tumor growth inhibition in the GBM xenografts. In summary, the present study provides pharmacological evidence that MTB has potential value in the treatment of GBM.

Chemotherapy with temozolomide (TMZ) is the traditional treatment for glioblastoma (GBM). Nevertheless, majority of GBM patients have recurrence from resistance to the chemotherapy. Herein, we examined combinational effects of MCCK1 (a specific and effective IKKε inhibitor) with TMZ in GBM U251MG and U‐87MG cell lines as well as U251MG xenograft models to overcome the therapeutic limitation of chemotherapy for GBM. Although MCCK1 alone showed inhibitory effects on in vitro proliferation, migration, invasion, and EMT of U251MG and U‐87MG cells, combination of MCCK1 and TMZ showed enhanced inhibitory effects. In the U251MG GBM xenograft models, MCCK1 showed synergistic therapeutic effects in combination with TMZ to reduce tumor volumes significantly. These data indicated that MCCK1 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for GBM.