Bladder microenvironment actuated proteomotors with ammonia amplification for enhanced cancer treatment

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

Biogenic gas vesicles labeled bone marrow mesenchymal stem cells: from synthesis to ultrasound imaging and tracking / 中华核医学与分子影像杂志

Objective:To fabricate biogenic gas vesicles (GVs)- polyethyleneimine (PEI)-marrow mesenchymal stem cells (BMSCs) and evaluate its potential on stem cell tracking with ultrasound imaging.Methods:GVs were cationized by PEI to fabricate GVs-PEI. The diameter and zeta potential of GVs-PEI were determined. GVs-PEI were co-incubated with BMSCs to obtain GVs-PEI-BMSCs and stem cell uptake was observed by fluorescence microscope. The cell viability of GVs-PEI-BMSCs was verified by cell counting kit-8 (CCK-8) assay were set. Ultrasound imaging was performed on 0, 2, 4 and 6 d in agarose phantom to evaluate ultrasound imaging capability of GVs-PEI-BMSCs group and BMSCs group in vitro. GVs-PEI-BMSCs and BMSCs were injected into quadriceps femoris of SD rats, and ultrasound imaging was performed on 0, 2, 4 and 6 d to evaluate the ultrasound imaging capability in vivo. One-way analysis of variance and independent-sample t test were used to analyze the data. Results:The diameter and zeta potential of GVs-PEI were (383.63±11.55) nm and (18.48±2.20) mV. Plenty of GVs-PEI were observed in GVs-PEI-BMSCs through microscope. When BMSCs were incubated with GVs-PEI in absorbance ( A) 500 nm of 0.5 and 1.0, there were no significant changes in the cell viability of GVs-PEI-BMSCs at 24, 48 and 72 h ( F values: 7.078-11.982, all P>0.05). Compared with BMSCs, GVs-PEI-BMSCs showed better ultrasound imaging capability in vitro in all time points with still significantly different signal at 6 d (634.29±10.78 vs 2 864.51±100.86; t=-121.86, P<0.001). The ultrasound imaging capability of GVs-PEI-BMSCs in vivo was much better than that of BMSCs at each time point with still significantly different signal at 6 d (2 108.02±217.96 vs 267.71±7.87; t=-121.39, P<0.001). Conclusion:GVs-PEI-BMSCs are successfully fabricated with the advantages of significant ultrasound imaging capability, long duration and safety, which provide a brand-new means for stem cells tracking in vivo.

Research progress on nonspecific immune microenvironment in breast cancer / 浙江大学学报·医学版

The immune microenvironment plays an important role in the occurrence and development of breast cancer. The infiltrating immune cells and the produced inflammatory cytokines in the tumor microenvironment regulate the growth, proliferation and metastasis of breast cancer. In this article, the roles and related mechanisms of nonspecific immune microenvironment in breast cancer are summarized, focusing on the natural killer cells, dendritic cells, myeloid derived suppressor cells, tumor associated macrophages, interleukins, chemokines, tumor necrosis factor-α, transforming growth factor-β and so on.

Effects of Deoxyschisandrin on Hemorrheology and Coagulation Function in Ulcerative Colitis Mice / 现代生物医学进展

Objective:To observe the effects of Deoxyschisandrin on hemorrheology and coagulation function in ulcerative colitis (UC)mice.Methods:Trinitrobenzenesulfonic acid (TNBS)induced UC mice model was prepared.And then UC mice were randomly divided into model group,positive control group,high,medium,and low dose groups of deoxyschisandrin (80,40,20mg/kg),and in addition,a normal control group was set up.There were 10 mice in each group respectively.UC mice were intragastricly administrated with different concentration of deoxyschisandrin in medication group,or with equal volume distilled water in normal group or model group,respectively.The blood viscosity was determined by blood rheometer,and the bleeding time (BT)and the clotting time (CT)were also observed through the methods of tail cutting and blood coagulation in glass plates accordingly.Results:Compared with model group,the BT (P ＜ 0.01)and CT (P ＜ 0.05)were significantly prolonged,and the blood viscosity was decreased obviously (P ＜ 0.05) in UC mice after administrated with different concentration deoxyschisandfin for 14 days.And the effects in high dose group were strongest and similar to those in the positive group.Conclusions:Deoxyschisandrin can improve hemorrheology and coagulation function in UC mice.

Ardipusilloside-I stimulates gastrointestinal motility and phosphorylation of smooth muscle myosin by myosin light chain kinase

Ardipusilloside-I is a natural triterpenoid saponin, which was isolated from Ardisia pusilla A. DC. The aim of the study was to evaluate the stimulation of ardipusilloside-I on gastrointestinal motility in vitro and in vivo. The experiment of smooth muscle contraction directly monitored the contractions of the isolated jejunal segment (IJS) in different contractile states, and the effects of ardipusilloside-I on myosin were measured in the presence of Ca²⁺-calmodulin using the activities of 20 kDa myosin light chain (MLC₂₀) phosphorylation and myosin Mg²⁺-ATPase. The effects of ardipusilloside-I on gastro emptying and intestinal transit in constipation-predominant rats were observed, and the MLCK expression in jejuna of constipated rats was determined by western blot. The results showed that, ardipusilloside-I increased the contractility of IJS in a dose-dependent manner and reversed the low contractile state (LCS) of IJS induced by low Ca²⁺, adrenaline, and atropine respectively. There were synergistic effects on contractivity of IJS between ardipusilloside-I and ACh, high Ca²⁺, and histamine, respectively. Ardipusilloside-I could stimulate the phosphorylation of MLC₂₀ and Mg²⁺-ATPase activities of Ca²⁺- dependent phosphorylated myosin. Ardipusilloside-I also stimulated the gastric emptying and intestinal transit in normal and constipated rats in vivo, respectively, and increased the MLCK expression in the jejuna of constipation-predominant rats. Briefly, the findings demonstrated that ardipusilloside-I could effectively excite gastrointestinal motility in vitro and in vivo.

DR bedside and CR bedside photographic quality comparative analysis in chest / 中华放射医学与防护杂志

Objective To explore the advantages of the bedside DR,taking the quality analysis of the chest image taken from the bedside digital radiography systems (DR) and computed radiography system (CR).Method All of the 900 pieces chest image taken by bedside DR,compared with the 900 pieces CR image randomly chosen.Results Bedside DR could further reduce the rate of the remake and the radiation dose,and provided more excellent image information.Conclusion The chest image taken by bedside DR has obviously advantage than CR.It can play a positive role in the diagnosis and treatment of the critical patient and surgical patient.