Effects of Pluronic F68 and Labrasol on the Intestinal Absorption and Pharmacokinetics of Rifampicin in Rats

Li Ma,Xin'an Wu,Yuhui Wei,Yan Zhou,Xiaohua Ma 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

The aim of this study was to investigate the effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin. Intestinal permeability of rifampicin with or without excipients was evaluated by an in situ single-pass perfusion method. A highperformance liquid chromatographic method was applied to study the pharmacokinetics of rifampicin with or without excipients. Labrasol or Pluronic F68 (0.1% and 0.05%, v/v), co-perfused with rifampicin (60 μg/mL), significantly increased in situ permeability. Similarly, verapamil (a typical P-gp inhibitor) also increased in situ permeability, but to a lesser extent. In vivo, the oral administration of rifampicin with or without Pluronic F68, Labrasol or verapamil resulted in statistically significant effect on t1/2 (4.83 to 7.75, 6.42 and 7.46 h) and total body clearance (0.46 to 0.26, 0.28, 0.24 L/h/kg). In addition, Pluronic F68, Labrasol and verapamil produced minor changes in AUC_0-t, which improved 1.55-, 1.54-, and 1.73-fold in comparison to control group, respectively. These results showed that Labrasol and Pluronic F68 might inhibit the function of P-gp in the intestine, thereby increasing intestinal absorption and changing the pharmacokinetic parameters of rifampicin. Therefore, excipient selection is an important factor to consider in rational formulation design.

Manufacturing of 3D Microlens Array Mold on Bulk Metallic Glass by Self-Aligned Multi-Ball Hot Embossing

Xiaohua Liu,Ruodong Mo,Kangsen Li,Jun She,Jiang Ma,Feng Gong 한국정밀공학회 2021 International Journal of Precision Engineering and Vol.8 No.4

Bulk metallic glasses (amorphous alloys) exhibiting both high hardness and extraordinary thermoplastic forming ability, are perfect mold material for 3D optical microlens array. However, conventional 3D micro fabrication for metallic glass requires Si templates which are extremely costly and eco-unfriendly to machine and demold. In this study, we report a green and lowcost self-aligned multi-ball hot embossing process to create 3D micro dimple array on metallic glass by replicating spherical crowns of self-aligned precision balls. A 3D metallic glass micro dimple array with aperture of 867.2 μm and surface roughness of 8.2 nm was fabricated in 30 s. Different from conventional hot embossing that material full-filled into mold, the new process enables micro dimple fabrication with different specifications by freely controlling the down displacement of balls. Therefore, the relationship between down displacement and depth of micro dimple was revealed through exploring the material flow behavior by a verified FE model. In addition, to test the feasibility of the fabricated metallic glass mold, a PMMA compound eye structure was embossed and its focusing and imaging performance were subsequently evaluated. This research demonstrates a new manufacturing process for rapid fabrication of 3D microlens arrays metallic glass mold in a neat and economic way.

Engineered fibrotic liver-targeted truncated transforming growth factor β receptor type II variant for superior anti-liver fibrosis therapy

Manman Ma,Xiaohua Wang,Xiaohui Liu,Yang Han,Yanhui Chu,Yanzhong Guan,Haifeng Liu 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.3

Truncated transforming growth factor β receptor type II (tTβRII) is a promising anti-liver fibrotic candidate because it serves as a trap for binding excessive TGF-β1 by means of competing with wild type TβRII (wtTβRII). However, the widespread application of tTβRII for the treatment of liver fibrosis has been limited by its poor fibrotic liver-homing capacity. Herein, we designed a novel tTβRII variant Z-tTβRII by fusing the platelet-derived growth factor β receptor (PDGFβR)-specific affibody ZPDGFβR to the N-terminus of tTβRII. The target protein Z-tTβRII was produced using Escherichia coli expression system. In vitro and in vivo studies showed that Z-tTβRII has a superior specific fibrotic liver-targeting potential via the engagement of PDGFβR-overexpressing activated hepatic stellate cells (aHSCs) in liver fibrosis. Moreover, Z-tTβRII significantly inhibited cell migration and invasion, and downregulated fibrosis- and TGF-β1/Smad pathway-related protein levels in TGF-β1-stimiluated HSC-T6 cells. Furthermore, Z-tTβRII remarkably ameliorated liver histopathology, mitigated the fibrosis responses and blocked TGF-β1/Smad signaling pathway in CCl4-induced liver fibrotic mice. More importantly, Z-tTβRII exhibits a higher fibrotic liver-targeting potential and stronger anti-fibrotic effects than either its parent tTβRII or former variant BiPPB-tTβRII (PDGFβR-binding peptide BiPPB modified tTβRII). In addition, Z-tTβRII shows no significant sign of potential side effects in other vital organs in liver fibrotic mice. Taken together, we conclude that Z-tTβRII with its a high fibrotic liver-homing potential, holds a superior anti-fibrotic activity in liver fibrosis in vitro and in vivo, which may be a potential candidate for targeted therapy for liver fibrosis.

cDNA Cloning and Expression Analysis of a Novel Human F-Box Only Protein

Haipeng Cheng,Yushu Ma,Xiaohua Ni,Min Jiang,Lingchen Guo,Wei Jin,Weiwen Xu,Gentao Cao,Chaoneng Ji,Kang Ying,Shaohua Gu,Yuhong Ma,Yi Xie,Yumun Mao 한국분자세포생물학회 2002 Molecules and cells Vol.14 No.1

F-box proteins are an expanding family of eukaryotic proteins that are characterized by an approximately 40 amino acid motif. Some F-box proteins are critical for the controlled degradation of cellular regulatory proteins. During a large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA clone that encodes a novel F-box protein. It showed a 90.0% identity with the previously isolated mouse F-box protein16 at the amino acid level. Northern blot analysis showed no detectable expression, while re-verse transcription-polymerase chain reaction analysis indicated that FBXO16 was expressed in the heart, spleen, and colon. By mapping, we localized the FBXO16 gene to the human chromosome 8p12. The FBXO16 gene consisted of 9 exons that spanned 67,816 bp of human genomic DNA.

Isolation, Identification, and Expression of Microbial Cellulases from the Gut of Odontotermes formosanus

( Jiwei Duan ),( Jun Liu ),( Xueling Ma ),( Yue Zhang ),( Xiaohua Wang ),( Kai Zhao ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.1

Termites are destructive to agriculture, forestry, and buildings, but they can also promote agro-ecosystem balance through the degradation of lignocellulose. Termite-triggered cellulose digestion may be clarified through microbial metabolism of cellulose products. In the present study, we characterized the activities of cellulase and its three components synthesized by the cellulase-producing fungal strain HDZK-BYTF620 isolated from the gut of Odontotermes formosanus. The protein components of cellulases were synthesized by strain HDZK-BYTF620, which were isolated and characterized using polyacrylamide gel electrophoresis, and the expression of the cellulases was studied at the proteome level.

Isolation, Purification, and Identification of Taxol and Related Taxanes from Taxol-Producing Fungus Aspergillus niger subsp. taxi

( Dan Li ),( Dongwei Fu ),( Yue Zhang ),( Xueling Ma ),( Liguo Gao ),( Xiaohua Wang ),( Dongpo Zhou ),( Kai Zhao ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.8

The content of taxol in the bark of yews is very low, and this is not affordable from the environmental point of view. Thus, it is a necessity to look for alternative sources of taxol production to solve its supply. Currently, a large portion of the taxol in the market comes from chemical semi-synthesis, but the semi-synthetic precursors such as baccatin III and 10- deacetyl-baccatin III are extracted from needles and twigs of yew trees. Taxol-producing fungi as a renewable resource is a very promising way to increase the scale of taxol production. Our group has obtained a taxol-producing endophytic fungus, Aspergillus niger subsp. taxi HD86-9, to examine if A. niger can produce the taxanes. Six compounds from the fermentation broth of strain HD86-9 were isolated and identified by ¹H NMR, ¹³C NMR, and ESI-MS. The results showed that the six compounds included four taxane diterpenoids (taxol, cephalomannine, baccatin III, and 10-deacetyl-baccatin III) and two non-taxane compounds (β-sitosterol and flavonoid isovitexin). The study verified that the taxanes can be produced by the A. niger, which is very important to taxol production via chemical semi-synthesis. Additionally, the finding is potentially very significant to solve the taxol semi-synthetic precursors extracted from needles and twigs of yew trees, and the precursor production can be easily increased through the culture condition optimization, genetic breeding, and metabolic engineering of the A. niger.

Measurement of TOF of fast neutrons with ²³⁸U target

Li, Meng,Guan, Yuanfan,Lu, Chengui,Zhang, Junwei,Yuan, Xiaohua,Duan, Limin,Yang, Herun,Hu, Rongjiang,He, Zhiyong,Wei, Xianglun,Ma, Peng,Gan, Zaiguo,Yang, Chunli,Zhang, Hongbin,Chen, Liang,Qiu, Tianli Korean Nuclear Society 2021 Nuclear Engineering and Technology Vol.53 No.6

We developed a Dual-PPACs detector for fast neutron measurements that consists of two sets of PPAC: conventional PPAC and fission PPAC. A²³⁸U(U₃O₈) coating is placed in the fission PPAC's anode, which is used as the neutrons conversion layer. An experiment was performed to measure neutron time-of-flight (TOF) in which ²⁵²Cf spontaneous fission source was used. An excellent time resolution of 164ps has been observed at 6 mbar in isobutene gas. With the excellent time resolution of Dual-PPACs detector, exact neutron energy can be extracted from the timing measurement. The experimental detection efficiency was 1.9 × 10^-7, consistent with the efficiency of 2.5 × 10^-7 given by a Geant4 simulation. Ultimately, the results show that the Dual-PPACs detector is a suitable candidate for measuring fast neutrons in the future CiADS system.