1.Synthesis of a new chitosan derivative and assay of Escherichia coli adsorption
Bingbing SHANG ; Jun SHA ; Yang LIU ; Qin TU ; Manlin LU ; Jinyi WANG
Journal of Pharmaceutical Analysis 2011;01(1):39-45
A new chitosan derivative is prepared using chitosan.Ethyl chlorocarbonate was first introduced to the hydroxyl group of phthaloylchitosan through a nucleophilic reaction.Hydrazine was then added to recover the amino groups of chitosan and promote cross-linking.The structure of this new chitosan derivative was characterized by Fourier transform infrared(FT-IR)and proton nuclear magnetic resonance(1H NMR)spectroscopy,and its physical properties were determined by X-ray diffraction(XRD),differential scanning calorimetry(DSC),and thermogravimetric analysis(TGA).The thermal and chemical stabilities of the new derivative were improved compared with those of native chitosan.Assay of Escherichia coli adhesion on a film based on this chitosan derivative showed good adsorption and biofilm formation.
2.Effects of gabapentin on high voltage active calcium currents in injured dorsal root ganglion neurons in a rat model of neuropathic pain
Xiaodong CHEN ; Minmin ZHU ; Shanshan AN ; Qiang WANG ; Liang LU ; Qin SUN ; Hang XIAO ; Jianguo XU ; Manlin DUAN
Chinese Journal of Anesthesiology 2010;30(1):56-59
Objective To investigate the effect of gabapentin on high voltage active calcium currents in the injured dorsal root ganglion (DRG) neurons in a rat model of neuropathic pain.Methods Pathogen-free male SD rats aged 4-6 weeks were used in this study. The animals were anesthetized with intraperitoneal pentobarbital soclium 50 mg/kg. L_5 spinal nerve was ligated between DRG and sciatic nerve and cut distal to the ligature. The animals were decapitated on the 14th postoperative day. L_5 DRG was isolated and the neurons in the ganglion were enzymatically dissociated. The high voltage active calcium current was recorded using whole-cell patch-clamp technique.Results Gabapentin inhibited the peak calcium current in the injured DEG neurons. Peak calcium current was decreased by gabapentin 100 μmol/L and both activation and steady-state inactivation curve shifted to more hyperpolarized potentials. Conclusion Gabapentin can inhibit high voltage active in the injured DRG neurons in a rat model of neuropathic pain. The alteration in the inactivation of the electrophysiological properties may be involved in the mechanism.
3.Comparative study on fracture toughness of digital light processing three-dimensional printing zirconia and milled zirconia
Yuxin LOU ; Yuqing LU ; Ziyu MEI ; Manlin SUN ; Jikui SUN ; Haiyang YU
Chinese Journal of Stomatology 2021;56(7):639-645
Objective:To investigate the influence of digital light processing (DLP) and computer numerical controlmilling (CNC) on the mechanical behavior of zirconia.Methods:Prepared DLP samples (experimental group, n=52) and CNC samples (control group, n=52) with 12 samples in each group were randomly selected using random number table to measure density, grain size and crystal phase composition. According to the different methods fracture toughness test, the samples were divided into indentation method group (IM) and single-edge-V-notch-beam group (SEVNB), with 30 DLP and 30 CNC samples in IM group, 10 DLP and 10 CNC samples in SEVNB group. The IM group was tested under three different loads (49.03 N, 98.07 N, 196.10 N), there were 10 samples for each load and each sample was tested at 15 points, and the load with the ratio of crack length to indentation diagonal length greater than 2.5 was selected as the indentation load to calculate its IM fracture toughness. At the same time, the SEVNB group was tested with four point bending test to record the maximum load at the time of fracture and calculate the SEVNB fracture toughness. Finally, the indentation and fracture surface were observed using optical microscope and scanning electron microscope, and the results of DLP group and CNC group were further compared to explore the difference in fracture mechanism. Results:The microstructure of DLP and CNC zirconia was basically the same, the density of DLP group was (6.020±0.021) g/cm 3, the grain size was (0.603±0.033) μm; the density of CNC group was (6.038±0.012) g/cm 3, the grain size was (0.591±0.033) μm. Both groups were composed of tetragonal zirconia. The load of 196.10 N was chosen as the indentation load for two groups to calculate the IM fracture toughness. In terms of fracture toughness, there was no significant difference between the two groups ( P>0.05). Scanning electron microscope images of fracture surface showed the intergranular fracture was the leading fracture mode of two groups. The IM and SEVNB fracture toughness of DLP zirconia were (6.111±0.179) MPa·m 1/2 and (7.221±0.809) MPa·m 1/2, respectively. The IM and SEVNB fracture toughness of CNC zirconia were (6.126±0.383) MPa·m 1/2 and (7.408±0.533) MPa·m 1/2, respectively. Conclusions:The microstructure of DLP and CNC zirconia is almost the same, and there is little difference in the fracture toughness of zirconia between two processing technologies.
4.Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-β-induced epithelial-mesenchymal transition via directly targeting TGFβR1.
Jingnan ZHANG ; Ze ZHANG ; Zhenlin HUANG ; Manlin LI ; Fan YANG ; Zeqi WU ; Qian GUO ; Xiyu MEI ; Bin LU ; Changhong WANG ; Zhengtao WANG ; Lili JI
Acta Pharmaceutica Sinica B 2023;13(7):2990-3007
As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.