Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy

Xianghui Li,Haoran Wang,Zhiyan Li,Dandan Li,Xiaofeng Lu,Shichao Ai,Yuxiang Dong,Song Liu,Jinhui Wu,Wenxian Guan 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: Mitochondria play an essential role in cellular redox homeostasis maintenance and meanwhile serve as an important target for organelle targeted therapy. Photodynamic therapy (PDT) is a promising strategy for organelle targeted therapy with noninvasive nature and highly spatiotemporal selectivity. However, the efficacy of PDT is not fully achieved due to tumor hypoxia. Moreover, aerobic respiration constantly consumes oxygen and leads to a lower oxygen concentration in mitochondria, which continuously limited the therapeutic effects of PDT. The lack of organelle specific oxygen delivery method remains a main challenge. Methods: Herein, an Oxygen Tank is developed to achieve the organelle targeted synergistic hypoxia reversal strategy, which not only act as an oxygen storage tank to open sources and reduce expenditure, but also coated with red blood cell membrane like the tank with stealth coating. Within the oxygen tank, a mitochondrion targeted photosensitizer (IR780) and a mitochondria respiration inhibitor (atovaquone, ATO) are co-loaded in the RBC membrane (RBCm) coated perfluorocarbon (PFC) liposome core. Results: Inside these bio-mimic nanoparticles, ATO effectively inhibits mitochondrial respiration and economized endogenous oxygen consumption, while PFC supplied high-capacity exogenous oxygen. These Oxygen modulators reverse the hypoxia status in vitro and in vivo, and exhibited a superior anti-tumor activity by mitochondria targeted PDT via IR780. Ultimately, the anti-tumor effects towards gastric cancer and colon cancer are elicited in vivo. Conclusions: This oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.

MiR-29a and MiR-140 Protect Chondrocytes against the Anti-Proliferation and Cell Matrix Signaling Changes by IL-1β

Li, Xianghui,Zhen, Zhilei,Tang, Guodong,Zheng, Chong,Yang, Guofu Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.2

As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-$1{\beta}$. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-$1{\beta}$ on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abundance of MMP13 and restore the type II collagen release in IL-$1{\beta}$ treated chondrocytes. Compared with single miRNA transfection, cotransfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-$1{\beta}$, thereby suggesting potent synergistic action. These results provided1novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

Characterization of the Hot Deformation Behaviour of an As-Extruded Al–Cu–Li Alloy by Constitutive Analysis

Xusheng Yang,Weijiu Huang,Xianghui Zhu,Ran Zhang,Fei Guo,Li Hu 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.11

The true stress–strain curves of an as-extruded state AA2099 were determined by uniaxial compression tests under varioushot deformation regimes. Constitutive analysis of the curves allowed calculation of the hot deformation activation energy(QHW). The microstructure of the as-compressed specimens were also characterized by electron back scatter diffraction(EBSD). EBSD data analyses showed that the major restoration mechanism corresponding to common industrial extrusionregimes was dynamic recovery. The precipitates in three states (T83, as-homogenized, and as-extruded) were characterizedby X-ray diffraction (XRD) phase analyses and transmission electron microscopy. The results revealed that the QHWwasclosely relevant to the precipitates strengthening. The finite element method simulation results and the microstructure of theextruded products confirmed that AA2099 in as-extruded state possessed good workability.

MiR-29a and MiR-140 Protect Chondrocytes against the Anti-Proliferation and Cell Matrix Signaling Changes by IL-1beta

Guofu Yang,Xianghui Li,Zhilei Zhen,Guodong Tang,Chong Zheng 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.2

As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously af-fects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-1. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-1 on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abun-dance of MMP13 and restore the type II collagen release in IL-1 treated chondrocytes. Compared with single miRNA transfection, co-transfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-1, thereby suggesting potent synergistic action. These results provided novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

The Clinical Characteristic and Management of Patients with Nocardiosis in a Tertiary Hospital in China

Liu Peilin,Wang Zhiqian,Jian Zijuan,Liu Xuan,Li Yanming,Yan Qun,Zhong Baiyun,Liao Mengting,Liang Xianghui,Liu Wenen 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.5

Nocardiosis is an uncommon opportunistic bacterial infection which becomes a significant health problem due to its increasing incidence and high mortality rate. However, many nocardiosis patients are underdiagnosed by physicians. To summarize the clinical characteristics and management of nocardiosis would help with better diagnosis and prognosis of nocardiosis. This retrospective study was conducted based on the medical records of nocardiosis patients between January 2015 and December 2021 in a tertiary hospital in China. Overall, 44 nocardiosis patients with 54 specimens were included. The patients consisted of 26 males and 18 females with a mean age of 50.4 ± 13.2 years. Among 44 patients, 26 (59.1%) were previously given immunosuppressive therapy. Connective tissue diseases (CTDs) were the most common underlying disease (16/44). The most frequent infection sites were the lungs (17/44) and skin or soft tissues (8/44). Common symptoms included cough (23/44), expectoration (18/44), fever (15/44), and subcutaneous abscesses (15/44). Forty-five out of 54 specimens (83.3%) required over 48 hours of culture time for nocardiosis detection. Thirty-six patients were cured or improved, 5 patients were discharged from the hospital due to poor prognosis, and 1 patient died. The average diagnosis time of poor prognosis cases was 19.7 days, which was significantly longer than those of improved or cured patients (7.3 days). Immunosuppressed patients comprise a large part of nocardiosis cases, which is worth attention in clinical practice. Early diagnosis, specifically through prolonged cultivation time of specimen, could help achieve better prognosis of nocardiosis patients.

Observation and characterization of the effect of electron cyclotron waves on toroidal rotation in EAST L-mode discharges

CHEN, Jun,HU, Ruiji,LYU, Bo,WANG, Fudi,WANG, Xiaojie,XU, Handong,LI, Yingying,FU, Jia,YIN, Xianghui,WU, Dajun,LIU, Fukun,ZANG, Qing,LIU, Haiqing,SHI, Yuejiang,MAO, Shifeng,YU, Yi,WAN, Baonian,YE, Miny IOP Publishing 2017 Plasma science & technology Vol.19 No.10

Bacillus subtilis Spore Surface Display Technology: A Review of Its Development and Applications

( Guoyan Zhang ),( Yingfeng An ),( Hossain M. Zabed ),( Qi Guo ),( Miaomiao Yang ),( Jiao Yuan ),( Wen Li ),( Wenjin Sun ),( Xianghui Qi ) 한국미생물 · 생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.2

Bacillus subtilis spore surface display (BSSD) technology is considered to be one of the most promising approaches for expressing heterologous proteins with high activity and stability. Currently, this technology is used for various purposes, such as the production of enzymes, oral vaccines, drugs and multimeric proteins, and the control of environmental pollution. This paper presents an overview of the latest developments in BSSD technology and its application in protein engineering. Finally, the major limitations of this technology and future directions for its research are discussed.