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Aim: To investigate the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor activator, on body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. Methods: A total of 328 Chinese overweight and obese type 2 diabetic patients were included in this multi-center, open-labeled and self-controlled clinical study. The patients were subcutaneously injected with liraglutide once daily for 24 weeks as add-on therapy to their previous hypoglycemic treatments. Statistical analyses were performed using SPSS software package version 11.5 for Windows. Results: Liraglutide treatment caused significant reduction of the mean body weight (from 86.61±14.09 to 79.10±13.55 kg) and waist circumference (from 101.81±13.96 to 94.29±14.17 cm), resulting in body weight lose of 5%-10% in 43.67% patients, and body weight loss above 10% in 34.06% patients, who had significant lower plasma creatinine levels. Baseline waist circumference, BMI and HOMA-IR were independently correlated with the body weight loss. Furthermore, liraglutide treatment significantly decreased HbA1c levels (from 8.66%±2.17% to 6.92%±0.95%) with HbA1c<7.0% in 35.37% patients, who had a significantly lower baseline level of HbA1c, but higher baseline levels of C peptide and glucagon. Moreover, liraglutide treatment resulted in greater body weight loss in patients with a long duration of diabetes, and better glycemic control in patients with a short duration of diabetes. Conclusion: Liraglutide significantly reduces body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. Patients with apparent visceral obesity, insulin resistance and a long duration of diabetes may have greater body weight loss; whereas patients with high insulin-secreting ability, hyperglucagonemia, and short-duration diabetes may obtain better glycemic control with liraglutide.

Background Clinical studies have shown that the efficacy of programmed cell death receptor-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors on glioblastoma (GBM) is much lower than what is expected because of the low immunogenicity of GBM. Ferroptosis of cancer cells can induce the maturation of dendritic cells (DC cells) and increase the activity of T cell. The activated T cells release IFN-γ, which subsequently induces the ferroptosis of cancer cells. Thus, the aim of this paper is to set up a new GBM-targeted drug delivery system (Fe3O4-siPD-L1@M-BV2) to boost ferroptosis for immunotherapy of drug-resistant GBM. Results Fe3O4-siPD-L1@M-BV2 significantly increased the accumulation of siPD-L1 and Fe2+ in orthotopic drug-resistant GBM tissue in mice. Fe3O4-siPD-L1@M-BV2 markedly decreased the protein expression of PD-L1 and increased the ratio between effector T cells and regulatory T cells in orthotopic drug-resistant GBM tissue. Moreover, Fe3O4-siPD-L1@M-BV2 induced ferroptosis of GBM cells and maturation of DC cell, and it also increased the ratio between M1-type microglia and M2-type microglia in orthotopic drug-resistant GBM tissue. Finally, the growth of orthotopic drug-resistant GBM in mice was significantly inhibited by Fe3O4-siPD-L1@M-BV2. Conclusion The mutual cascade amplification effect between ferroptosis and immune reactivation induced by Fe3O4-siPD-L1@M-BV2 significantly inhibited the growth of orthotopic drug-resistant GBM and prolonged the survival time of orthotopic drug-resistant GBM mice. Graphical Abstract

Introduction To evaluate efficacy and safety data of dulaglutide in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with 1–2 oral antihyperglycemic medications (OAMs). Methods This is a subgroup analysis of a phase 3, open-label, randomized, parallel-arm, 52-week study in Chinese patients aged ≥ 18 years with T2DM who had inadequate glycemic control with OAMs (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤ 11.0%). The primary endpoint was assessment of the noninferiority of dulaglutide 1.5 mg as measured by change in HbA1c, compared with insulin glargine (glargine), using a 0.4% noninferiority margin at week 26. Results A total of 607 patients from China were randomized 1:1:1 to once-weekly dulaglutide 1.5 or 0.75 mg or once-daily glargine. At week 26, the least squares mean (LSM) change from baseline in HbA1c was greater with dulaglutide 1.5 mg (− 1.67%) and dulaglutide 0.75 mg (− 1.31%) compared with glargine (− 1.11%). The LSM (95% confidence interval) for the difference of dulaglutide 1.5 mg and 0.75 mg vs glargine was − 0.56% (− 0.75 to − 0.37) and − 0.20% (− 0.39 to − 0.01), respectively. Both doses of dulaglutide were noninferior and superior to glargine at 26 weeks and 52 weeks (two-sided P value < 0.05). The mean body weight decreased ( P < 0.001) and total hypoglycemia rates were lower ( P < 0.05) in the dulaglutide groups compared with the glargine group. Gastrointestinal adverse events (AEs) were the most frequently reported AEs in dulaglutide groups. Conclusion Both doses of dulaglutide are efficacious and tolerable in Chinese patients with T2DM who had inadequate glycemic control on OAMs. Trial Registration ClinicalTrials.gov identifier, NCT01648582. Funding Eli Lilly and Company. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-0646-y) contains supplementary material, which is available to authorized users.

Glioblastoma (GBM) is an invasive cancer with high mortality in central nervous system. Resistance to temozolomide (TMZ) and immunosuppressive microenvironment lead to low outcome of the standardized treatment for GBM. In this study, a 2-deoxy-d-glucose modified lipid polymer nanoparticle loaded with TMZ and siPD-L1 (TMZ/siPD-L1@GLPN/dsb) was prepared to reprogram the TMZ-resistant and immunosuppressive microenvironment in orthotopic GBM. TMZ/siPD-L1@GLPN/dsb simultaneously delivered a large amount of TMZ and siPD-L1 to the deep area of the orthotopic TMZ-resistant GBM tissue. By inhibiting PD-L1 protein expression, TMZ/siPD-L1@GLPN/dsb markedly augmented the percentage of CD3+CD8+IFN-γ+ cells (Teff cells) and reduced the percentage of CD4+CD25+FoxP3+ cells (Treg cells) in orthotopic TMZ-resistant GBM tissue, which enhanced T-cell mediated cytotoxicity on orthotopic TMZ-resistant GBM. Moreover, TMZ/siPD-L1@GLPN/dsb obviously augmented the sensitivity of orthotopic TMZ-resistant GBM to TMZ through decreasing the protein expression of O 6-methyl-guanine-DNA methyltransferase (MGMT) in TMZ-resistant GBM cells. Thus, TMZ/siPD-L1@GLPN/dsb markedly restrained the growth of orthotopic TMZ-resistant GBM and extended the survival time of orthotopic GBM rats through reversing a TMZ-resistant and immunosuppressive microenvironment. TMZ/siPD-L1@GLPN/dsb shows potential application to treat orthotopic TMZ-resistant GBM.

Aim: To prepare pH-sensitive nanoparticle composed of alendronate (ALN) and poly(amidoamine) (PAMAM) to treat bone metastases of lung cancer. Methods: The solvent evaporation method was used to prepare docetaxel (DTX)-loaded ALN-PAMAM nanoparticles (DTX@ALN-PAMAM). Results: The in vitro results showed DTX@ALN-PAMAM significantly enhanced the anticancer activity of DTX and inhibited the formation of osteoclasts. DTX@ALN-PAMAM concentrated at bone metastasis site in mice, which resulted in the suppression of bone resorption, pain response and growth of bone metastases. Eventually, the therapeutic effect of DTX on bone metastases of lung cancer was obviously improved. Conclusion: ALN modified PAMAM nanoparticle could be an effective platform for the treatment of bone metastases of lung cancer.

Background Ischemic stroke is one of the main causes of death and disability in the world. The treatment for ischemic stroke is to restore blood perfusion as soon as possible. However, when ischemic brain tissue is re-perfused by blood, the mitochondrial permeability transition pore (mPTP) in neuron and microglia is excessively opened, resulting in the apoptosis of neuron and nerve inflammation. This aggravates nerve injury. Cyclosporine A (CsA) inhibits the over-opening of mPTP, subsequently reducing the release of ROS and the apoptosis of cerebral ischemia/reperfusion injured neuron and microglia. However, CsA is insoluble in water and present in high concentrations in lymphatic tissue. Herein, cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury. Results CsA@HFn efficiently penetrated the blood-brain barrier (BBB) and selectively accumulated in ischemic area, inhibiting the opening of mPTP and ROS production in neuron. This subsequently reduced the apoptosis of neuron and the damage of BBB. Consequently, CsA@HFn significantly reduced the infarct area. Moreover, CsA@HFn inhibited the recruitment of astrocytes and microglia in ischemic region and polarized microglia into M2 type microglia, which subsequently alleviated the nerve inflammation. Conclusions CsA@HFn showed a significant therapeutic effect on cerebral ischemia/reperfusion injury by alleviating the apoptosis of neuron, nerve inflammation and the damage of BBB in ischemic area. CsA@HFn has great potential in the treatment of ischemic stroke. Graphical Abstract

Background At present, patients with myocardial infarction remain an increased risk for myocardial ischemia/reperfusion injury (MI/RI). There lacks effectively method to treat MI/RI in clinic. For the treatment of MI/RI, it is still a bottleneck to effectively deliver drug to ischemic myocardium. In this paper, a regulatory T cells (Tregs) biomimetic nanoparticle (CsA@PPTK) was prepared by camouflaging nanoparticle with platelet membrane. Results CsA@PPTK actively accumulated in ischemic myocardium of MI/RI mice. CsA@PPTK significantly scavenged reactive oxygen species (ROS) and increased the generation of Tregs and the ratio of M2 type macrophage to M1 type macrophage in ischemic myocardium. Moreover, CsA@PPTK significantly attenuated apoptosis of cardiomyocytes and reduced the infarct size and fibrosis area in ischemic myocardium. CsA@PPTK markedly decreased the protein expression of MMP-9 and increased the protein expression of CX43 in ischemic myocardium tissue. Subsequently, the remodeling of the left ventricle was significant alleviated, and heart function of MI/RI mice was markedly improved. Conclusion CsA@PPTK showed significant therapeutic effect on MI/RI, and it has great potential application in the treatment of MI/RI. Graphical Abstract