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1.
Drug Des Devel Ther ; 14: 5611-5622, 2020.
Article in English | MEDLINE | ID: mdl-33376305

ABSTRACT

PURPOSE: Pulmonary surfactants (eg, sinapultide) are widely used for the treatment of lung injury diseases; however, they generally induce poor therapeutic efficacy in clinics. In this study, sinapultide-loaded microbubbles (MBs) were prepared and combined with ultrasound (US) treatment as a new strategy for improved treatment of lung injury diseases. METHODS: The combination treatment strategy of MBs combined with ultrasound was tested in a lipopolysaccharide (LPS)-induced mouse model of alveolar epithelial cells (AT II) and acute lung injury. Firstly, cytotoxicity, cytokines, and protein levels in LPS-mediated AT II cells were assessed. Secondly, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, cytokines, and protein levels in LPS-mediated acute lung injury mice after treatment with the MBs were evaluated. Moreover, histology examination of the heart, liver, spleen, lung and kidney of mice treated with the MBs was performed to initially evaluate the safety of the sinapultide-loaded MBs. RESULTS: Sinapultide-loaded MBs in combination with ultrasound treatment significantly reduced the secretion of inflammatory cytokines and increased the expression of surfactant protein A (SP-A) in AT II cells. Furthermore, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and SP-A expression level of mice treated with MBs and ultrasound were significantly improved compared to those of non-treated mice. In addition, the histology of the examined organs showed that the MBs had a good safety profile. CONCLUSION: Sinapultide-loaded MBs combined with ultrasonic treatment may be a new therapeutic option for lung injury diseases in the clinic.


Subject(s)
Acute Lung Injury/drug therapy , Lipopolysaccharides/antagonists & inhibitors , Peptides/therapeutic use , Ultrasonic Waves , Acute Lung Injury/chemically induced , Animals , Male , Mice , Mice, Inbred BALB C , Microbubbles
2.
Chin Med ; 13: 47, 2018.
Article in English | MEDLINE | ID: mdl-30214471

ABSTRACT

BACKGROUND: Polysaccharides are carbohydrate chains composed of linked monosaccharide units. Accumulating studies report that polysaccharides isolated from Dendrobium officinale have a variety of functions. However, the composition and anti-tumor activity of D. officinale grown in the Huoshan area are largely unknown. METHODS: A polysaccharide (DOPA-1) was isolated from D. officinale by hot water extraction and ethanol precipitation, followed by purification via DEAE-cellulose and Sephadex G-100 chromatography. DOPA-1 was analyzed by infrared and nuclear magnetic resonance and then characterized by periodate oxidation and Smith degradation. The anti-tumor activity of DOPA-1 was then tested in HepG-2 cells. RESULTS: Our results show that DOPA-1 is mainly comprised of mannose, glucose, and galactose at a molar ratio of 1:0.42:0.27 and has an average molecular weight of 2.29 × 105 Da. Additionally, DOPA-1 inhibited HepG-2 cell growth in a dose-dependent manner. DOPA-1-treated HepG-2 cells also had increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential. Furthermore, apoptosis was observed in DOPA-1-treated HepG-2 cells along with Bcl-2 downregulation and Bax upregulation at the protein level. CONCLUSIONS: Our findings suggest that DOPA-1 induces apoptosis in tumor cells via altered mitochondrial function, ROS production, and altered apoptosis-related protein expression. This bioactive polysaccharide could, therefore, potentially be further developed as an anti-tumor adjuvant drug.

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