Publications by authors named "Yunchun Zhao"

11 Publications

  • Page 1 of 1

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer.

Front Oncol 2021 22;11:650453. Epub 2021 Apr 22.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Increasing evidence shows that the extracellular matrix (ECM) is an important regulator of breast cancer (BC). The ECM comprises of highly variable and dynamic components. Compared with normal breast tissue under homeostasis, the ECM undergoes many changes in composition and organization during BC progression. Induced ECM proteins, including fibrinogen, fibronectin, hyaluronic acid, and matricellular proteins, have been identified as important components of BC metastatic cells in recent years. These proteins play major roles in BC progression, invasion, and metastasis. Importantly, several specific ECM molecules, receptors, and remodeling enzymes are involved in promoting resistance to therapeutic intervention. Additional analysis of these ECM proteins and their downstream signaling pathways may reveal promising therapeutic targets against BC. These potential drug targets may be combined with new nanoparticle technologies. This review summarizes recent advances in functional nanoparticles that target the ECM to treat BC. Accurate nanomaterials may offer a new approach to BC treatment.
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http://dx.doi.org/10.3389/fonc.2021.650453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100244PMC
April 2021

Preparation of olmesartan medoxomil solid dispersion with sustained release performance by mechanochemical technology.

Drug Deliv Transl Res 2021 Apr 15. Epub 2021 Apr 15.

National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.

Hypertension is a common disease for human with high morbidity and mortality, and olmesartan medoxomil (OM) is widely used in the therapy of hypertension. However, poor water solubility and low bioavailability limit its widespread use. To improve the effect of OM, a ternary OM solid dispersion consisting of hydroxypropyl-β-cyclodextrin (HP-β-CD) and hydroxypropyl methylcellulose (HPMC) was prepared by mechanochemical method. The best preparation parameters were OM/HP-β-CD/HPMC-E5 with mass ratio of 1:2.6:1 and milling time of 4 h. Under the optimal preparation conditions, the solubility of the ternary solid dispersion could be increased by 12 times as compared with pure OM. Due to the addition of HPMC-E5, the solid dispersion had sustained release performance with prolonged release time of 12 h. Furthermore, in vivo study demonstrated that the prepared solid dispersion could afford significantly improved bioavailability of ~ 3-fold in comparison with pure drug. Hence, the prepared ternary solid dispersion of OM may be a promise delivery system for clinical application.
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http://dx.doi.org/10.1007/s13346-021-00959-wDOI Listing
April 2021

Preparation and Biological Property Evaluation of Novel Cationic Lipid-Based Liposomes for Efficient Gene Delivery.

AAPS PharmSciTech 2021 Jan 3;22(1):22. Epub 2021 Jan 3.

Pharmacy Department, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.

Novel cationic lipid-based liposomes prepared using an amphiphilic cationic lipid material, N,N-dimethyl-(N',N'-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSP), have been proposed to enhance the transfection of nucleic acids. Herein, we designed and investigated liposomes prepared using DMSP, soybean phosphatidylcholine, and cholesterol. This novel gene vector has high gene loading capabilities and excellent protection against nuclease degradation. An in vitro study showed that the liposomes had lower toxicity and superior cellular uptake and transfection efficiency compared with Lipofectamine 2000. An endosomal escape study revealed that the liposomes demonstrated high endosomal escape and released their genetic payload in the cytoplasm efficiently. Mechanistic studies indicated that the liposome/nucleic acid complexes entered cells through energy-dependent endocytosis that was mediated by fossa proteins. These results suggest that such cationic lipid-based liposome vectors have potential for clinical gene delivery.
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http://dx.doi.org/10.1208/s12249-020-01868-wDOI Listing
January 2021

Investigation of hub genes involved in diabetic nephropathy using biological informatics methods.

Ann Transl Med 2020 Sep;8(17):1087

Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China.

Background: The aim of this study was to find genes with significantly aberrant expression in diabetic nephropathy (DN) and determine their underlying mechanisms.

Methods: GSE30528 and GSE1009 were obtained by querying the Gene Expression Omnibus (GEO) database. The difference in target gene expression between normal renal tissues and kidney tissues in patients with DN was screened by using the GEO2R tool. Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, differentially expressed genes (DEGs) were analysed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then, the protein-protein interactions (PPIs) of DEGs were analyzed by Cytoscape with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes in this PPI network were recognized by centrality analysis.

Results: There were 110 genes with significant expression differences between normal and DN tissues. The differences in gene expression involved many functions and expression pathways, such as the formation of the extracellular matrix and the construction of the extracellular domain. The correlation analysis and subgroup analysis of 14 hub genes and the clinical characteristics of DN showed that CTGF, ALB, PDPN, FLT1, IGF1, WT1, GJA1, IGFBP2, FGF9, BMP2, FGF1, BMP7, VEGFA, and TGFBR3 may be involved in the progression of DN.

Conclusions: We confirmed the differentially expressed hub genes and other genes which may be the novel biomarker and target candidates in DN.
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http://dx.doi.org/10.21037/atm-20-5647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575993PMC
September 2020

Sustained delivery of 17β-estradiol by human amniotic extracellular matrix (HAECM) scaffold integrated with PLGA microspheres for endometrium regeneration.

Drug Deliv 2020 Dec;27(1):1165-1175

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The endometrial injury usually results in intrauterine adhesions (IUAs). However, there is no effective treatment to promote the regeneration of the endometrium currently. The decellularized amnion membrane (AM) is a promising material in human tissue repair and regeneration due to its biocompatibility, biodegradability, as well as the preservation of abundant bioactive components. Here, an innovative drug-delivering system based on human amniotic extracellular matrix (HAECM) scaffolds were developed to facilitate endometrium regeneration. The 17β-estradiol (E) loaded PLGA microspheres (E-MS) were well dispersed in the scaffolds without altering their high porosity. E released from E-MS-HAECM scaffolds showed a decreased initial burst release followed with a sustained release for 21 days, which coincided with the female menstrual cycle. Results of cell proliferation suggested E-MS-HAECM scaffolds had good biocompatibility and provided more biologic guidance of endometrial cell proliferation except for mechanical supports. Additionally, the mRNA expression of growth factors in endometrial cells indicated that HAECM scaffolds could upregulate the expression of EGF and IGF-1 to achieve endometrium regeneration. Therefore, these advantages provide the drug-loaded bioactive scaffolds with new choices for the treatments of IUAs.
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http://dx.doi.org/10.1080/10717544.2020.1801891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470125PMC
December 2020

Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia: a literature review of pharmaceutical and clinical aspects.

Eur J Hosp Pharm 2020 Jun 26. Epub 2020 Jun 26.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Objectives: The rate of dermal toxicity has been shown to increase in patients receiving pegylated liposomal doxorubicin (PLD), particularly palmar-plantar erythrodysesthesia (PPE). However, it is difficult to diagnose and treat PLD-related PPE due to its delayed dermal performance, unclear pathogenetic mechanism, and the lack of specific preventive measures. The aim of this study was to provide potential management strategies for PPE associated with PLD.

Methods: The current article reviews the available data regarding the pharmacological and clinical aspects of PLD, including the formulation and pharmacokinetics of PLD, dose and schedule contribution to PPE, concomitant drugs affecting skin toxicity of PLD, the pathogenesis of PPE, and preventive measures and treatment of PLD-related PPE.

Results: The long circulation structure of polyethylene glycol liposomes may be one of the reasons for PPE. PLD has radically different pharmacokinetic characteristics, including prolonged blood circulation time, decreased body distribution volume, and slow clearance. Altering the schedules and doses of PLD or combining it with platinum compounds can optimise clinical efficacy and minimise the occurrence of PPE. Doses of 150-200 mg of pyridoxine daily have been widely used for the prevention and treatment of PPE. Regional cooling and plasma filtration have been used for PPE prophylaxis.

Conclusions: To date, the mechanism of PPE induced by PLD remains unclear, and no complete preventive medication has been established. Further research and prospective randomised studies are needed to understand the management options in PLD-related PPE.
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http://dx.doi.org/10.1136/ejhpharm-2020-002311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077615PMC
June 2020

Targeted GSH-exhausting and hydroxyl radical self-producing manganese-silica nanomissiles for MRI guided ferroptotic cancer therapy.

Nanoscale 2020 Aug;12(32):16738-16754

Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.

Ferroptosis, a cell death path induced by the generation of reactive oxygen species (ROS), will cause the accumulation of lipid peroxides (PL-PUFA-OOH) and achieve potent tumor-regression. However, glutathione (GSH)-dependent glutathione peroxidase 4 (GPx4) can reduce PL-PUFA-OOH and antagonize the ferroptosis inducing effect of ROS. Herein, folate-PEG modified dihydroartemisinin (DHA) loaded manganese doped mesoporous silica nanoparticles (described as nanomissiles) were constructed for integrating the effect of GSH exhaustion and ROS generation. After endocytosis by tumor cells, intracellular GSH triggered the degradation of nanomissiles, which allowed the simultaneous release of DHA and Fenton catalytic Mn2+ due to the redox reaction between the manganese-oxygen bonds and GSH. The degradation would lead to GSH exhaustion, activation of Mn2+-based magnetic resonance imaging (MRI), and DHA-driven ˙OH generation. The GSH-free environment inhibited the activity of GPx4 and enhanced the accumulation of PL-PUFA-OOH oxidized by ˙OH. Furthermore, the cooperative effects suppressed tumor metastasis by destroying the structure of polyunsaturated fatty acids in the cell membranes and showed potent antitumor activity. This innovative ferroptotic therapy integrating the GSH exhaustion and ROS generation will be a promising strategy for cancer therapy.
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http://dx.doi.org/10.1039/d0nr02396eDOI Listing
August 2020

The Role of Microbiomes in Pregnant Women and Offspring: Research Progress of Recent Years.

Front Pharmacol 2020 8;11:643. Epub 2020 May 8.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Pregnancy is a complicated and delicate process, the maternal body undergoes changes on hormones, immunity, and metabolism during pregnancy to support fetal development. Microbiomes in the human body mainly live in the intestine, and the human gut microbiomes are complex, which composed of more than 500 to 1500 different bacteria, archaea, fungi, and viruses. Studies have shown that these microbiomes are not only involved in the digestion and absorption of food but also indispensable in regulating host health. In recent years, there has been increasing evidence that microbiomes are important for pregnant women and fetuses. During pregnancy, there will be great changes in gut microbiomes. Regulating gut microbiomes is beneficial to the health of the mother and the fetus. In addition, many complications during pregnancy are related to gut microbiomes, such as gestational diabetes, obesity, preeclampsia, digestive disorders, and autoimmune diseases. Moreover, the microbiomes in mother's milk and vagina are closely related to the colonization of microbiomes in the early life of infants. In this review, we systematically review the role of maternal microbiomes in different gestational complications, and elucidate the function and mechanism of maternal microbiomes in the neural development and immune system of offspring. These will provide a clear knowledge framework or potential research direction for researchers in related fields.
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http://dx.doi.org/10.3389/fphar.2020.00643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225329PMC
May 2020

Multiple Drug Transporters Contribute to the Placental Transfer of Emtricitabine.

Antimicrob Agents Chemother 2019 08 25;63(8). Epub 2019 Jul 25.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Emtricitabine (FTC) is a first-line antiviral drug recommended for the treatment of AIDS during pregnancy. We hypothesized that transporters located in the placenta contribute to FTC transfer across the blood-placenta barrier. BeWo cells, cell models with stable or transient expression of transporter genes, primary human trophoblast cells (PHTCs), and small interfering RNAs (siRNAs) were applied to demonstrate which transporters were involved. FTC accumulation in BeWo cells was reduced markedly by inhibitors of equilibrative nucleoside transporters (ENTs), concentrative nucleoside transporters (CNTs), organic cation transporters (OCTs), and organic cation/carnitine transporter 1 (OCTN1) and increased by inhibitors of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs). ENT1, CNT1, OCTN1, MRP1/2/3, and BCRP, but not ENT2, CNT3, OCTN2, or multidrug resistance protein 1 (MDR1), were found to transport FTC. FTC accumulation in PHTCs was decreased significantly by inhibitors of ENTs and OCTN1. These results suggest that ENT1, CNT1, and OCTN1 probably contribute to FTC uptake from maternal circulation to trophoblasts and that ENT1, CNT1, and MRP1 are likely involved in FTC transport between trophoblasts and fetal blood, whereas BCRP and MRP1/2/3 facilitate FTC transport from trophoblasts to maternal circulation. Coexistence of tenofovir or efavirenz with FTC in the cell medium did not influence FTC accumulation in BeWo cells or PHTCs.
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http://dx.doi.org/10.1128/AAC.00199-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658773PMC
August 2019

Taxanes in combination with platinum derivatives for the treatment of ovarian cancer during pregnancy: A literature review
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Int J Clin Pharmacol Ther 2017 Sep;55(9):753-760

Ovarian cancer is one of the most common types of solid carcinoma diagnosed during pregnancy. Taxane plus a platinum derivative is a combination therapy that is predominantly used in the treatment of ovarian cancer in non-pregnant women. Pregnancy adds various complexities to a course of treatment. In pregnant patients diagnosed with cancer during the first trimester, the risks of fetal malformations and fetal loss increase following the administration of cytotoxic drugs, and this is higher with multi-agent vs. single-agent chemotherapy (~ 25 vs. 10%). Exposure during the second and third trimester has little influence on teratogenic effects but increases the risk of intrauterine growth retardation, prematurity, low birth weight, and bone marrow toxicity. The present study aimed to review the maternal and fetal safety of treatment with taxane plus platinum derivatives for ovarian cancer during pregnancy. Relevant literature was retrieved from the Embase and PubMed databases using the search terms "ovarian cancer", "pregnancy", "taxane", "paclitaxel", "docetaxel", "platinum", "cisplatin", and "carboplatin". All available data up until September 2016 was synthesized, with no language restrictions. A total of 11 articles (including 13 pregnancies and 14 newborns) were retrieved that reported on the use of standard-dose taxane and platinum chemotherapy, including 9 cases treated with paclitaxel and carboplatin, 3 cases treated with paclitaxel and cisplatin, and 1 case treated with docetaxel and cisplatin. In 13 of the 14 (92.9%) births included, a healthy neonate was born, with follow-up ranging from 2 to 160 months. The average weight of the neonates at the time of delivery was 2,442.1 g. In 7 of 9 the case reports that provided survival data, the mother was alive and disease-free at the end of follow-up (ranging from 2 to 40 months). In conclusion, combination therapy with taxanes and a platinum derivative may play a significant role in the management of pregnant patients with ovarian cancer during the second and third trimester. Exposure to this combination of agents during the second and third trimester does not appear to have a significant bearing on fetal mortality and abortion.
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http://dx.doi.org/10.5414/CP202995DOI Listing
September 2017

Knockdown of STAT3 expression in SKOV3 cells by biodegradable siRNA-PLGA/CSO conjugate micelles.

Colloids Surf B Biointerfaces 2015 Mar 28;127:155-63. Epub 2015 Jan 28.

Women's Hospital, Medicine of School, Zhejiang University, Hangzhou 310006, China.

Biodegradable and biocompatible poly(d,l-lactic-co-glycolic acid) (PLGA)was conjugated to the 5'-thiol end of signal transducer and activator of transcription 3 (STAT3) small interfering RNA (STAT3-siRNA) via a disulfide bond. In aqueous environments, these siRNA-PLGA conjugates can spontaneously form core/shell type spherical micelles with a particle size of about 200 nm. A biodegradable, low molecular weight cationic polymer, chitosan oligosaccharide (CSO), was added to the siRNA-PLGA micelles at different nitrogen to phosphate (N/P) ratios to form stable, spherical siRNA-PLGA/CSO micelles with sizes of 150-180 nm. The siRNA-PLGA/CSO micelles were produced via ionic complexation between negatively charged siRNA and positively charged CSO on the outer shell of the micelles. The siRNA-PLGA/CSO micelles exhibited superior cellular uptake and STAT3 gene silencing efficiency in SKOV3 ovarian cancer cells when compared with siRNA/CSO complexes at the same N/P ratios with no significant differences with lipofectamine 2000. Furthermore, the siRNA-PLGA/CSO micelles showed that the efficiencies of cellular uptake and STAT3 gene silencing gradually increased with increasing N/P ratios. The siRNA-PLGA/CSO micelles also inhibited the growth of SKOV3 cells, as well as, promoted apoptosis of the cells. These results indicate that siRNA-PLGA/CSO micelles can be utilized as a novel and efficient siRNA carrier to treat a variety of diseases.
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http://dx.doi.org/10.1016/j.colsurfb.2015.01.034DOI Listing
March 2015