Publications by authors named "Weifen Zhang"

37 Publications

Chemotherapeutic drug-induced immunogenic cell death for nanomedicine-based cancer chemo-immunotherapy.

Nanoscale 2021 Oct 13. Epub 2021 Oct 13.

College of Pharmacy, Weifang Medical University, Weifang 261053, China.

Chemotherapy has been a conventional paradigm for cancer treatment, and multifarious chemotherapeutic drugs have been widely employed for decades with significant performances in suppressing tumors. Moreover, some of the antitumor chemotherapeutic agents, such as doxorubicin (DOX), oxaliplatin (OXA), cyclophosphamide (CPA) and paclitaxel (PTX), can also tackle tumors through the induction of immunogenic cell death (ICD) in tumor cells to trigger specific antitumor immune responses of the body and improve chemotherapy efficacy. In recent years, chemo-immunotherapy has attracted increasing attention as one of the most promising combination therapies to struggle with malignant tumors. Many effective antitumor therapies have benefited from the successful induction of ICD in tumors, which could incur the release of endogenous danger signals and tumor-associated antigens (TAAs), further stimulating antigen-presenting cells (APCs) and ultimately initiating efficient antitumor immunity. In this review, several well-characterized damage-associated molecular patterns (DAMPs) were introduced and the progress of ICD induced by representative chemotherapeutic drugs for nanomedicine-based chemo-immunotherapy was highlighted. In addition, the combination strategies involving ICD cooperated with other therapies were discussed. Finally, we shared some perspectives in chemotherapeutic drug-induced ICD for future chemo-immunotherapy. It was hoped that this review would provide worthwhile presentations and enlightenments for cancer chemo-immunotherapy.
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http://dx.doi.org/10.1039/d1nr05512gDOI Listing
October 2021

Nanosized FeS/ZnS heterojunctions derived using zeolitic imidazolate Framework-8 (ZIF-8) for pH-universal oxygen reduction and High-efficiency Zn-air battery.

J Colloid Interface Sci 2021 Oct 2;608(Pt 1):446-458. Epub 2021 Oct 2.

School of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, PR China. Electronic address:

Low-cost, stable, and highly active electrocatalysts for oxygen reduction reaction (ORR), especially for pH-universal ORR, are vital for developing numerous renewable energy devices. Herein, a hierarchical N, S-codoped porous carbon-based catalyst (ZFP-800) coupled with abundant FeS/ZnS heterojunctions was facilely prepared via direct pyrolysis of a Ferrocene-crosslinked pyrrole hydrogel composited with zeolitic imidazolate framework-8 (ZIF-8) templates. Compared with the heterojunction-free catalytic activity, the ZFP-800 catalytic activity was significantly higher in pH-universal ranges. Moreover, the ZFP-800 exhibited competitive ORR performance to commercial Pt/C (20%) in various electrolytes, in terms of onset (E), half-wave potentials (E), limiting current density (J), durability, and methanol immunity. For instance, it exhibited super ORR catalytic activity on E and E, and exceeded that of the benchmark Pt/C in both the alkaline and neutral media. Furthermore, the application of ZFP-800 as a cathode catalyst in a home-made Zn-air battery demonstrated its operation capability in ambient conditions with a competitive performance on the specific energy density (828 mA·h·g), maximum discharge power density (205.6 mW·cm), rate performance, and the long-term stability (188 h at 5 mA·cm). This study can facilitate the development of advanced heterojunction-based materials for renewable energy applications.
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http://dx.doi.org/10.1016/j.jcis.2021.09.134DOI Listing
October 2021

Sequentially pH-Responsive Drug-Delivery Nanosystem for Tumor Immunogenic Cell Death and Cooperating with Immune Checkpoint Blockade for Efficient Cancer Chemoimmunotherapy.

ACS Appl Mater Interfaces 2021 Sep 10;13(37):43963-43974. Epub 2021 Sep 10.

College of Pharmacy, Weifang Medical University, Weifang 261053, China.

Chemoimmunotherapy has anchored a new blueprint for cancer management. As a burgeoning approach, immunotherapy has shifted the paradigm of traditional chemotherapy and opened up new prospects for cancer treatment. Here, a sequentially pH-responsive doxorubicin (DOX) delivery nanosystem is designed for simultaneous chemotherapy and tumor immunogenic cell death (ICD). DOX is modified into pH-sensitive -aconityl-doxorubicin (CAD) for being easily adsorbed by polycationic polyethylenimine (PEI), and the PEI/CAD complexes are in situ-shielded by aldehyde-modified polyethylene glycol (PEG). The PEG/PEI/CAD nanoparticles (NPs) can keep stable in neutral physiological pH during systemic circulation but will detach PEG shielding once in slightly acidic tumor extracellular pH. The exposed positive PEI/CAD complexes are endocytosed effortlessly, and CAD is then converted back to DOX by endosomal-acidity-triggered -aconityl cleavage. The released DOX further elicits ICD, and the moribund tumor cells will release antigens and damage-associated molecular patterns to recruit dendritic cells and activate antitumor immunity. An excellent therapeutic effect is achieved when the immune checkpoint PD-1 antibody (aPD-1) is utilized to cooperate with the PEG/PEI/CAD NPs for blocking tumor immune escape and maintaining antitumor activity of the ICD-instigated T cells. The sequentially pH-responsive DOX delivery nanosystem cooperating with immune checkpoint blockade will provide a potential strategy for cancer chemoimmunotherapy.
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http://dx.doi.org/10.1021/acsami.1c10643DOI Listing
September 2021

CpG-Based Nanovaccines for Cancer Immunotherapy.

Int J Nanomedicine 2021 5;16:5281-5299. Epub 2021 Aug 5.

College of Pharmacy, Weifang Medical University, Weifang, 261053, People's Republic of China.

Cancer has been a serious health hazard to the people all over the world with its high incidence and horrible mortality. In recent years, tumor vaccines in immunotherapy have become a hotspot in cancer therapy due to their many practical advantages and good therapeutic potentials. Among the various vaccines, nanovaccine utilized nanoparticles (NPs) as the carrier and/or adjuvant has presented significant therapeutic effect in cancer treatment. For tumor nanovaccines, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) is a commonly used adjuvant. It has been reported that CpG ODN was the most effective immune stimulant among the currently known adjuvants. It could be recognized by toll-like receptor 9 (TLR9) to activate humoral and cellular immunity for preventing or treating cancer. In this review, the topic of CpG-based nanovaccines for cancer immunotherapy will be focused. The types and properties of different CpG will be introduced in detail first, and then some representative tumor nanovaccines will be reviewed according to the diverse loading modes of CpG, such as electrostatic adsorption, covalent bonding, hydrophilic and hydrophobic interaction, and DNA self-assembly, for summarizing the current progress of CpG-based tumor nanovaccines. Finally, the challenges and future perspectives will be discussed. It is hoped that this review will provide valuable references for the development of nanovaccines in cancer immunotherapy.
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http://dx.doi.org/10.2147/IJN.S317626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352601PMC
August 2021

Selective thermotherapy of tumor by self-regulating photothermal conversion system.

J Colloid Interface Sci 2022 Jan 30;605:752-765. Epub 2021 Jul 30.

College of Pharmacy, Weifang Medical University, Weifang 261053, China; Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang 261053, China; Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang 261053, China. Electronic address:

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.
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http://dx.doi.org/10.1016/j.jcis.2021.07.134DOI Listing
January 2022

Bilayer Membrane Composed of Mineralized Collagen and Chitosan Cast Film Coated With Berberine-Loaded PCL/PVP Electrospun Nanofiber Promotes Bone Regeneration.

Front Bioeng Biotechnol 2021 19;9:684335. Epub 2021 Jul 19.

Department of Microbiology, Weifang Medical University, Weifang, China.

Bone defects are difficult to repair and reconstruct as bone regeneration remains technically challenging, with exogenous factors required to accelerate this process. Biodegradable synthetic scaffolds are promising materials for stimulating bone tissue repair. In this study, we investigated whether a bilayer membrane that includes mineralized collagen (MC) and chitosan (CS) delivering berberine (BER)-a typical Chinese herbal monomer-could promote bone healing in a rat model. An MC/CS cast film was coated with polycaprolactone (PCL)/polyvinylpyrrolidone (PVP) electrospun nanofibers loaded with BER, yielding the [email protected]/PVP-MC/CS bilayer membrane. The 3-dimensional structure had nanofibers of uniform diameter and showed good hydrophilicity; the bilayer membrane showed favorable mechanical properties. [email protected]/PVP-MC/CS enhanced the proliferation and attachment of MC3T3-E1 cells and induced bone regeneration when implanted into a rat femoral bone defect. These findings provide evidence that [email protected]/PVP-MC/CS has clinical potential for effective bone repair.
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http://dx.doi.org/10.3389/fbioe.2021.684335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327095PMC
July 2021

Berberine for bone regeneration: Therapeutic potential and molecular mechanisms.

J Ethnopharmacol 2021 Sep 29;277:114249. Epub 2021 May 29.

College of Pharmacy, Weifang Medical University, Weifang, 261053, PR China; Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, 261053, Shandong, PR China; Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang, Shandong, 261053, PR China. Electronic address:

Ethnopharmacological Relevance: Berberine is a quaternary ammonium isoquinoline alkaloid, mainly extracted from plants berberaceae, papaveraceae, ranunculaceae and rutaceae such as coptis chinensis Franch, Phellodendron chinense, and berberis pruinosa. The plants are extensively used in traditional medicine for treating infection, diabetes, arrhythmia, tumor, osteoporosis et al. Pharmacological studies showed berberine has effects of anti-inflammation, anti-tumor, lower blood lipid, lower blood glucose, anti-osteoporosis, anti-osteoarthritis et al. AIM OF THE STUDY: This review aims to summarize the application of natural herbs that contain berberine, the further use and development of berberine, the effects as well as mechanism of berberine on osteoblasts and osteoclasts, the recent advances of in vivo studies, in order to provide a scientific basis for its traditional uses and to prospect of the potential applications of berberine in clinics.

Method: The research was achieved by retrieving from the online electronic database, including PubMed, Web of Science, Google Scholar and China national knowledge infrastructure (CNKI). Patents, doctoral dissertations and master dissertations are also searched.

Results: Berberine has a long history of medicinal use to treat various diseases including bone disease in China. Recent studies have defined its function in promoting bone regeneration and great potential in developing new drugs. But the systemic mechanism of berberine on bone regeneration still needs more research to clarify.

Conclusion: This review has systematically summarized the application, pharmacological effects, mechanism as well as in vivo studies of berberine and herbs which contain berberine. Berberine has a definite effect in promoting the proliferation and differentiation of osteoblasts as well as inhibiting the production of osteoclasts to promote bone regeneration. However, the present studies about the system mechanisms and pharmacological activity of berberine were incomplete. Applying berberine for new drug development remains an exciting and promising alternative to bone regeneration engineering, with broad potential for therapeutic and clinical practice.
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http://dx.doi.org/10.1016/j.jep.2021.114249DOI Listing
September 2021

Dual Modal Imaging-Guided Drug Delivery System for Combined Chemo-Photothermal Melanoma Therapy.

Int J Nanomedicine 2021 18;16:3457-3472. Epub 2021 May 18.

Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang, 261053, People's Republic of China.

Purpose: Malignant melanoma is one of the most devastating types of cancer with rapid relapse and low survival rate. Novel strategies for melanoma treatment are currently needed to enhance therapeutic efficiency for this disease. In this study, we fabricated a multifunctional drug delivery system that incorporates dacarbazine (DTIC) and indocyanine green (ICG) into manganese-doped mesoporous silica nanoparticles (MSN(Mn)) coupled with magnetic resonance imaging (MRI) and photothermal imaging (PI), for achieving the superior antitumor effect of combined chemo-photothermal therapy.

Materials And Methods: MSN(Mn) were characterized in terms of size and structural properties, and drug loading and release efficiency MSN(Mn)-ICG/DTIC were analyzed by UV spectra. Photothermal imaging effect and MR imaging effect of MSN(Mn)-ICG/DTIC were detected by thermal imaging system and 3.0 T MRI scanner, respectively. Then, the combined chemo-phototherapy was verified in vitro and in vivo by morphological evaluation, ultrasonic and pathological evaluation.

Results: The as-synthesized MSN(Mn) were characterized as mesoporous spherical nanoparticles with 125.57±5.96 nm. MSN(Mn)-ICG/DTIC have the function of drug loading-release which loading ratio of ICG and DTIC could reach to 34.25±2.20% and 50.00±3.24%, and 32.68±2.10% of DTIC was released, respectively. Manganese doping content could reach up to 65.09±2.55 wt%, providing excellent imaging capability in vivo which the corresponding relaxation efficiency was 14.33 mMs. And outstanding photothermal heating ability and stability highlighted the potential biomedical applicability of MSN(Mn)-ICG/DTIC to kill cancer cells. Experiments by A375 melanoma cells and tumor-bearing mice demonstrated that the compound MSN(Mn)-ICG/DTIC have excellent biocompatibility and our combined therapy platform delivered a superior antitumor effect compared to standalone treatment in vivo and in vitro.

Conclusion: Our findings demonstrate that composite MSN(Mn)-ICG/DTIC could serve as a multifunctional platform to achieve a highly effective chemo-photothermal combined therapy for melanoma treatment.
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http://dx.doi.org/10.2147/IJN.S306269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144848PMC
June 2021

Fabrication and Characterization of Chitosan/Poly(Lactic-Co-glycolic Acid) Core-Shell Nanoparticles by Coaxial Electrospray Technology for Dual Delivery of Natamycin and Clotrimazole.

Front Bioeng Biotechnol 2021 5;9:635485. Epub 2021 Mar 5.

College of Pharmacy, Weifang Medical University, Weifang, China.

Natamycin (NAT) is the drug of choice for the treatment of fungal keratitis (FK). However, its inherent shortcomings, such as poor solubility, high dosing frequency, and long treatment cycle, need to be urgently addressed by designing a new delivery to widen its clinical utility. Growing research has confirmed that clotrimazole (CLZ) plays a significant role in fungal growth inhibition. Hence, coaxial electrospray (CO-ES) technology is used herein to prepare nano-systems with an average hydrodynamic particle size of 309-406 nm for the co-delivery of NAT and CLZ in chitosan (CTS) and poly(lactic-co-glycolic acid) (PLGA). The resulting NAT/[email protected]/PLGA formulations were characterized by a transmission electron microscope (TEM) and release test. The results show that the formulations had obvious core-shell structures, uniform particle distribution, and also can sustain the release of drugs over 36 h. Furthermore, hemolysis, corneal irritation test, local allergenic test, and antifungal activity analyses are performed to evaluate the safety and efficiency of the formulations. Thus, good biosafety along with a significant anti-candidiasis effect are found in the NAT/[email protected]/PLGA nanoparticles (NPs). Taken together, the results suggest that this design may provide a promising drug delivery system and a new option for the treatment of FK.
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http://dx.doi.org/10.3389/fbioe.2021.635485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973235PMC
March 2021

Fe(II) and Tannic Acid-Cloaked MOF as Carrier of Artemisinin for Supply of Ferrous Ions to Enhance Treatment of Triple-Negative Breast Cancer.

Nanoscale Res Lett 2021 Feb 23;16(1):37. Epub 2021 Feb 23.

College of Pharmacology, Weifang Medical University, Weifang, 261053, China.

Suppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer, which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Owing to its poor water solubility and limited intracellular iron content, it is challenging for further application in antitumor therapy. Herein, we developed ferrous-supply nano-carrier for ART based on tannic acid (TA) and ferrous ion (Fe(II)) coated on the zeolitic imidazolate framework-8 (ZIF) with ART encapsulated (TA-Fe/[email protected]) via coordination-driven self-assembly. Drug release experiments showed that ART was not nearly released in pH 7.4, while 59% ART was released in pH 5.0 after 10 h, demonstrating the excellent pH-triggered release. Meanwhile, a high level of intracellular ROS and MDA, accompanied with decreasing GSH and GPX4, displayed a newly developed nano-drug system displayed markedly enhanced ferroptosis. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated higher efficiency of tumor suppression of TA-Fe/[email protected] This work provides a novel approach to enhance the potency of ferroptotic nano-medicine and new directions for TBNC therapy.
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http://dx.doi.org/10.1186/s11671-021-03497-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902752PMC
February 2021

Targeted delivery of quercetin by nanoparticles based on chitosan sensitizing paclitaxel-resistant lung cancer cells to paclitaxel.

Mater Sci Eng C Mater Biol Appl 2021 Feb 25;119:111442. Epub 2020 Aug 25.

College of Pharmacy, Weifang Medical University, Weifang 261053, Shandong, PR China; Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang 261053, Shandong, PR China; Institute for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang 261053, Shandong, PR China. Electronic address:

Chemotherapy plays crucial roles in the clinical treatment of non-small cell lung cancer (NSCLC). Nevertheless, acquired chemoresistance is a common and critical problem that limits the clinical application of chemotherapy. Quercetin (QUE), a natural bioflavonoid, has significant antitumor potential, which has been verified in many drug-resistant cancer cell lines and animal models. Here, we explored whether QUE could reverse the resistance of NSCLC to paclitaxel (PTX)-based therapy. The results of cell viability revealed that QUE could synergistically enhance the cytotoxicity of PTX in A549 and A549/Taxol cells. Furthermore, Akt and ERK phosphorylation had no significant changes in A549/Taxol cells treated with PTX. However, it was significantly inhibited by the combination treatment of QUE and PTX. To improve the antitumor activity of PTX due to its hydrophobicity and eliminate its toxicity, we prepared targeted biodegradable cetuximab chitosan nanoparticles (Cet-CTS NPs) to deliver PTX and QUE using ionic cross-linking technique. The targeted NPs displayed a particle size of 290 nm and sustained release of PTX and QUE. In addition, the targeted Cet-CTS NPs loaded with PTX and QUE inhibited tumor growth in PTX-resistant A549/Taxol cells. Cet-QUE NPs decreased tumor growth in PTX-resistant xenografts. In conclusion, the administration of QUE by using Cet-CTS NPs could provide a prospective strategy for the treatment of PTX-resistant lung cancer.
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http://dx.doi.org/10.1016/j.msec.2020.111442DOI Listing
February 2021

MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells.

Cell Death Dis 2020 09 14;11(9):751. Epub 2020 Sep 14.

Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 261014, China.

Although ferroptosis has been recognized as a novel antitumoral treatment, high expression of nuclear factor erythroid 2-related factor 2 (NRF2) has been reported to be an antioxidant transcript factor that protects malignant cells from ferroptosis. Previous findings indicated that metallothionein 1D pseudogene (MT1DP), a long noncoding RNA (lncRNA), functioned to aggravate oxidative stress by repressing antioxidation. Here we aimed at assessing whether MT1DP could regulate erastin-induced ferroptosis on non-small cell lung cancer (NSCLC) and elucidating the mechanism. We found that ectopic expression of MT1DP sensitized A549 and H1299 cells to erastin-induced ferroptosis through downregulation of NRF2; in addition, ectopic MT1DP upregulated malondialdehyde (MDA) and reactive oxygen species (ROS) levels, increased intracellular ferrous iron concentration, and reduced glutathione (GSH) levels in cancer cells exposed to erastin, whereas downregulation of MT1DP showed the opposite effect. RNA pulldown assay and dual-luciferase reporter assay confirmed that MT1DP modulated the expression of NRF2 via stabilizing miR-365a-3p. As low solubility of erastin limits its efficient application, we further prepared folate (FA)-modified liposome (FA-LP) nanoparticles for targeted co-delivery of erastin and MT1DP to enhance the bioavailability and the efficiency of the drug/gene combination. Erastin/[email protected] (E/[email protected]) sensitized erastin-induced ferroptosis with decreased cellular GSH levels and elevated lipid ROS. In vivo analysis showed that E/[email protected] had a favorable therapeutic effect on lung cancer xenografts. In short, our findings identify a novel strategy to elevate erastin-induced ferroptosis in NSCLCs acting through the MT1DP/miR-365a-3p/NRF2 axis.
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http://dx.doi.org/10.1038/s41419-020-02939-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490417PMC
September 2020

Porous Organic Polymers as Fire-Resistant Additives and Precursors for Hyperporous Carbon towards Oxygen Reduction Reactions.

ChemistryOpen 2020 05 20;9(5):593-598. Epub 2020 May 20.

School of pharmacy Weifang Medical University Weifang 261053, Shandong P. R. China.

Cyclotriphosphazene (CP) based porous organic polymers (POPs) have been designed and prepared. The introduction of CP into the porous skeleton endowed special thermal stability and outstanding flame retardancy to prepared polymers. The nonflammable level of PNK-CMP fabricated via the condensation of 2,2'-(1,4-phenylene)diacetonitrile (DAN) and hexakis(4-acetylphenoxy)cyclotriphosphazene (HACTP) through Knoevenagel reaction, in vertical burning tests reached V-2 class (UL-94) and the limiting oxygen index (LOI) reached 20.8 %. When used as additive, PNK-CMP could suppress the dissolving out of PEPA effectively, reducing environment pollution and improving the flame retardant efficiency. The POP and PEPA co-added PU (m%: m%=5.0 %: 5.0 %) could not be ignited under simulated real-scale fire conditions. The nonflammable level of POP/PEPA/PU in vertical burning tests (UL-94) reached V-0 class with a LOI as high as 23.2 %. The smoke emission could also be suppressed, thus reducing the potential for flame spread and fire hazards. Furthermore, carbonization of PNK-CMP under the activation of KOH yield a hyperporous carbon (PNKA-800) with ultrahigh BET surface area (3001 m g) and ultramicropore size showing excellent ORR activity in alkaline conditions.
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http://dx.doi.org/10.1002/open.202000059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239271PMC
May 2020

Chemical characteristics and cytoprotective activities of polysaccharide fractions from Athyrium Multidentatum (Doll.) Ching.

Int J Biol Macromol 2020 May 10. Epub 2020 May 10.

Department of Pharmacy, Weifang Medical University, Weifang 261053, PR China.

Five polysaccharide fractions (PS-1, PS-2, PS-3, PS-4 and PS-5) were successfully isolated from Athyrium Multidentatum (Doll.) Ching by anion-exchange column chromatography. Their in vitro cytoprotective activities and the underlying mechanisms were explored in this paper. Chemical analysis suggested that the five polysaccharide fractions were heteropolysaccharides with different molecular weights and monosaccharide compositions. Treatment with these polysaccharide fractions could increase cell viabilities, superoxide dismutase/catalase activities, nitric oxide contents, mitochondrial membrane potential levels and Bcl-2/Bax ratios, and reduce cell apoptosis, intracellular reactive oxygen species production and malondialdehyde contents in HO-damaged cells. Moreover, these polysaccharide fractions enhanced the mRNA expression levels of PI3K, Akt, FOXO3a, Nrf2 and HO-1 and PS-4 exhibited the most powerful effects on the mRNA expression of these genes. Current findings suggested that the polysaccharide fractions decreased HO-induced apoptosis of HUVECs. The activation of PI3K/Akt/FOXO3a and Nrf2/HO-1 signaling pathways might be involved in the protective mechanisms of the active fractions. The polysaccharides might be one of the key bioactive ingredients of Athyrium Multidentatum (Doll.) Ching for the treatment of oxidative damage.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.053DOI Listing
May 2020

Cyclodextrin-Modified CeO Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis.

Int J Nanomedicine 2020 15;15:2515-2527. Epub 2020 Apr 15.

College of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People's Republic of China.

Purpose: Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate β-cyclodextrins (β-CDs)-modified ceria nanoparticles (β-CDs/CeO NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy.

Methods: The β-CDs/CeO NPs were synthesized by a hydrothermal method using unmodified β-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)- and catalase-mimetic activities, the in vitro antioxidant activity of the β-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression.

Results: The average particle size of the blank β-CDs/CeO NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasi-spherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce/Ce valence state. FTIR spectroscopy confirmed the presence of β-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of HO efficiency reached about 50% in the presence of 40 µg/mL, demonstrating excellent superoxide dismutase- and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, β-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of [email protected]β-CDs/CeO NPs under physiological conditions. In IMQ-induced psoriatic model, the [email protected]β-CDs/CeO NPs exhibited excellent therapeutic effect.

Conclusion: This study may pave the way for the application of nanozyme β-CDs/CeO NPs as a powerful tool for psoriasis therapy.
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http://dx.doi.org/10.2147/IJN.S246783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170634PMC
July 2020

Astragalus Polysaccharides/Chitosan Microspheres for Nasal Delivery: Preparation, Optimization, Characterization, and Pharmacodynamics.

Front Pharmacol 2020 18;11:230. Epub 2020 Mar 18.

School of Pharmacy, Weifang Medical University, Weifang, China.

Chitosan (CTS) constitutes a promising area in treatment of nose-related diseases as a nasal drug delivery carrier. Astragalus polysaccharide (APS) significantly attenuates eosinophils and neutrophil-dominant airway inflammation, and it has a potential pharmaceutical application in the treatment of severe asthma. The purpose of this work was to prepare APS/CTS microspheres intended for nasal drug delivery by the spray-drying method. The characteristics of APS/CTS microspheres were evaluated by a scanning electron microscope, Fourier transform infrared spectroscopy, differential scanning calorimetry, and drug release. The effect of APS/CTS microspheres on rats with allergic rhinitis (AR) was investigated by eosinophil and neutrophil counts in nasal lavage fluid. Results of SEM showed that microspheres were spherical and wrinkled. release showed that 67.48-93.76% APS was released from APS/CTS microspheres at pH 6.8 within 24 h. The effects showed that APS/CTS microspheres alleviated allergic symptoms and reduced eosinophils infiltration and the expression of interleukin-4 in the nasal mucosa tissue of rats that had no liver and kidney toxicity by hematoxylin-eosin staining observation. In conclusion, these results indicated that APS/CTS microspheres had excellent characteristics for the treatment of AR.
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http://dx.doi.org/10.3389/fphar.2020.00230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093564PMC
March 2020

Rebamipide-loaded chitosan nanoparticles accelerate prostatic wound healing by inhibiting M1 macrophage-mediated inflammation via the NF-κB signaling pathway.

Biomater Sci 2020 Feb 12;8(3):912-925. Epub 2019 Dec 12.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. and Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China.

A large proportion of benign prostatic hyperplasia (BPH) patients suffer from lower urinary tract symptoms after surgery due to the presence of prostatic urothelium wounds. Rebamipide (RBM) exerts wound healing promotion and anti-inflammatory effects on various tissues, including the urothelium. However, intravesical administration of RBM is hindered due to its low solubility and resulting unsustainable drug concentrations in the bladder. In this study, RBM-loaded chitosan nanoparticles (RBM/CTS NPs) were prepared using the ionic cross-linking method. Physicochemical characteristics and the wound healing promotion effect, as well as in vitro influence on macrophages were evaluated. The results show that RBM/CTS NPs are spherical with uniform size distribution, while slower and sustained in vitro release of RBM is presented. In vivo, faster wound healing and improved re-epithelialization progress were observed after treatment with RBM/CTS NPs in a model of thulium laser resection of the prostate (TmLRP). The degree of local inflammatory response decreased, as confirmed by decreasing numbers of pro-inflammatory M1 phenotype macrophages and levels of IL-1β, IL-6, IL-12 and TNF-α in the urine of canines. We also found that RBM/CTS NPs suppress macrophage M1 polarization induced by lipopolysaccharide and interferon-γ and inhibit the activation of the NF-κB signaling pathway. Therefore, as a novel therapeutic strategy, intravesical administration of RBM/CTS NPs can effectively avoid drug intolerance and drug wastage, accelerating the postoperative wound repairing of the prostatic urethra by suppressing macrophage M1 phenotype polarization.
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http://dx.doi.org/10.1039/c9bm01512dDOI Listing
February 2020

Acetaminophen sensitizing erastin-induced ferroptosis via modulation of Nrf2/heme oxygenase-1 signaling pathway in non-small-cell lung cancer.

J Cell Physiol 2020 04 20;235(4):3329-3339. Epub 2019 Sep 20.

Department of Pathology, Weifang Medical University, Weifang, Shandong, China.

Growing evidence confirms that ferroptosis plays an important role in tumor growth inhibition. However, some non-small-cell lung cancer (NSCLC) cell lines are less sensitive to erastin-induced ferroptotic cell death. Elucidating the mechanism of resistance of cancer cells to erastin-induced ferroptosis and increasing the sensitivity of cancer cells to erastin need to be addressed. In our experiment, erastin and acetaminophen (APAP) cotreatment inhibited NSCLC cell viability and promoted ferroptosis and apoptosis, accompanied with attenuation of glutathione and ectopic increases in lipid peroxides. Erastin and APAP promoted NSCLC cell death by regulating nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); and the ferroptosis induced by erastin and APAP was abrogated by bardoxolone methyl (BM) with less generation of reactive oxygen species and malondialdehyde. As a downstream gene of Nrf2, heme oxygenase-1 expression decreased significantly with the cotreatment of erastin and APAP, which could be rescued by BM. In vivo experiment showed that the combination of erastin and APAP had a synergic therapeutic effect on xenograft of lung cancer. In short, the present study develops a new effective treatment for NSCLC by synergizing erastin and APAP to induce ferroptosis.
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http://dx.doi.org/10.1002/jcp.29221DOI Listing
April 2020

Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells.

Cancer Sci 2019 Oct 3;110(10):3173-3182. Epub 2019 Oct 3.

Department of Pathology, Weifang Medical University, Weifang, China.

Ferroptosis is an iron-dependent, lipid peroxide-driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple-negative breast cancer (TNBC) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin-loaded exosomes labeled with folate (FA) to form FA-vectorized exosomes loaded with erastin ([email protected]) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti-tumor effect in vitro of [email protected] were determined. [email protected] could increase the uptake efficiency of erastin into MDA-MB-231 cells; compared with [email protected] and free erastin, [email protected] has a better inhibitory effect on the proliferation and migration of MDA-MB-231 cells. Furthermore, [email protected] promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that [email protected] suppressed expression of glutathione peroxidase 4 (GPX4) and upregulated expression of cysteine dioxygenase (CDO1). We conclude that targeting and biocompatibility of exosome-based erastin preparations provide an innovative and powerful delivery platform for anti-cancer therapy.
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http://dx.doi.org/10.1111/cas.14181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778638PMC
October 2019

A new mitochondrion targetable fluorescent probe for carbon monoxide-specific detection and live cell imaging.

Chem Commun (Camb) 2019 Aug;55(64):9444-9447

College of Pharmacy, College of Nursing, Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang 261053, China.

A new mitochondrion targetable molecular probe for carbon monoxide (CO)-specific detection based on palladium-free mediated opening of spirolactam was designed. The turn-on red fluorescence caused by CO enables a safe and powerful method for unravelling the function of CO in biological systems to be established.
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http://dx.doi.org/10.1039/c9cc03909kDOI Listing
August 2019

Transition from vesicles to nanofibres in the enzymatic self-assemblies of an amphiphilic peptide as an antitumour drug carrier.

Nanoscale 2019 Sep 25;11(33):15479-15486. Epub 2019 Jun 25.

School of Bioscience and Technology, Weifang Medical University, Weifang 261042, P. R. China.

Amphiphilic peptides modified by molecular design can self-assemble into specific nanostructures with interesting applications in the fields of biomedicine and biotechnology. Lysyl oxidase (LO) is ubiquitous in human serum. However, enzymatic self-assembly of amphiphilic peptides remains a challenge for lipid-soluble drug delivery under the induction of LO. Here, we designed a positively charged amphiphilic peptide, AK, that could stably self-assemble to form nanovesicles. The lysine in the peptide molecule could be covalently cross-linked under enzyme catalysis, and the major transition was from random coil to β-sheet secondary structures, eventually leading to the destruction of the peptide nanovesicles. The lipid-soluble antitumour drug doxorubicin (DOX) as a model drug could be loaded into the hydrophobic core of the nanovesicles formed by the amphiphilic peptide AK, even though DOX was not covalently linked to the peptide monomer. The amount of DOX-encapsulated AK nanovesicles in human hepatocellular carcinoma BEL-7402 cells was significantly higher than that in human liver L02 cells, indicating excellent selectivity. The amphiphilic peptide AK inhibited tumour cell growth and had low cytotoxicity to mammalian cells, and it showed antibacterial activity against G and G bacteria. These advantages make enzymatic self-assembling AK nanovesicles of great interest in drug delivery for biomedical applications.
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http://dx.doi.org/10.1039/c9nr02874aDOI Listing
September 2019

An Interpenetrating Porous Organic Polymer as a Precursor for FeP/Fe P-Embedded Porous Carbon toward a pH-Universal ORR Catalyst.

ChemSusChem 2019 Feb 25;12(4):915-923. Epub 2019 Jan 25.

School of Pharmacy, Weifang Medical University, Weifang, 261053, P.R. China.

Interpenetrating porous organic polymers (PNFc-POP) inspired by the structure of DNA were synthesized through a two-stage polymerization method under catalyst-free conditions. A ferrocene-rich hyper-crosslinked polymer (Fc-melamine) was interwoven with cyclotriphosphazene-based conjugated porous polymer (PN-CMP) to obtain an interconnected polymer network (PNFc-POP). The sequential interpenetrating polymer network contained a diverse range of heteroatoms (P, N, O and Fe) and exhibited a large BET surface area. Simple pyrolysis of the dual polymer interweaved skeletons at 900 °C afforded nanocrystalline FeP/Fe P-embedded N and P codoped porous carbon composites. The optimal catalyst obtained by the pyrolysis of PNFc-POP at 900 °C (PNFc-900) exhibited hierarchical porosity and large BET surface areas. It also exhibited excellent oxygen reduction reaction catalytic activities over the entire pH range. The onset potential (E =1.01 V) and half-wave potential (E =0.86 V) of PNFc-900 exceeded those of commercial Pt/C (E =0.99 V and E =0.84 V) in alkaline conditions. The obtained catalysts with a four-electron transfer pathway for the reduction of oxygen also displayed excellent long-term stability and methanol tolerance.
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http://dx.doi.org/10.1002/cssc.201802369DOI Listing
February 2019

Targeted p53 on Small-Molecules-Induced Ferroptosis in Cancers.

Front Oncol 2018 2;8:507. Epub 2018 Nov 2.

Department of Pathology, Weifang Medical University, Weifang, China.

Ferroptosis is a type of programmed cell death characterized by the accumulation of lipid reactive oxygen species (L-ROS) driven by the oxidative degeneration of lipids in an iron-dependent manner. The mechanism by which lipid oxidative degradation drives ROS-ferroptosis involves metabolic dysfunctions that result in impaired intracellular metabolic processes and ROS production. Recent studies have found that p53 acts as a positive regulator of ferroptosis by promoting ROS production. p53 directly regulates the metabolic versatility of cells by favoring mitochondrial respiration, leading to ROS-mediated ferroptosis. In mild stress, p53 protects cell survival via eliminating ROS; additionally, in human colorectal cancer, p53 antagonizes ferroptosis by formation of the DPP4-p53 complex. In short, the mechanisms of p53-mediated ROS production underlying cellular response are poorly understood. In the context of recent research results, the indistinct roles of p53 on ROS-mediated ferroptosis are scrutinized to understand the mechanism underlying p53-mediated tumor suppression.
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http://dx.doi.org/10.3389/fonc.2018.00507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224449PMC
November 2018

Paclitaxel-Loaded Core-Shell Magnetic Nanoparticles and Cold Atmospheric Plasma Inhibit Non-Small Cell Lung Cancer Growth.

ACS Appl Mater Interfaces 2018 Dec 10;10(50):43462-43471. Epub 2018 Dec 10.

College of Pharmacy , Weifang Medical University , Weifang 261053 , Shandong , China.

Nanoparticle-based drug delivery allows effective and sustained delivery of therapeutic agents to solid tumors and has completely changed how cancer is treated. As a new technology for medical applications, cold atmospheric plasma (CAP) shows a great potential in selective cancer treatment. The aim of this work is to develop a new dual cancer treatment approach by integrating CAP with novel paclitaxel (PTX)-loaded nanoparticles for targeting A549 cells. For this purpose, PTX-loaded core-shell magnetic nanoparticles were prepared through coaxial electrospraying, and various characteristics were investigated. Biodegradable poly(lactic- co-glycolic acid) was selected as the polymer shell to encapsulate the anticancer therapeutics. Results demonstrated a uniform size distribution and high drug encapsulation efficiency of the electrosprayed nanoparticles, which had sustained release characteristics and a variety of excellent properties. An in vitro study showed that PTX-loaded nanoparticles and CAP synergistically inhibited the growth of A549 cells more effectively than when each was used individually. We also found that CAP could induce the PTX-loaded nanoparticles in tumor cells to increase the effective drug concentration to a level that might be conducive to reduce drug resistance. Therefore, the integration of PTX-encapsulated nanoparticles and CAP provides a promising tool for the development of a new non-small cell lung cancer treatment strategy.
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http://dx.doi.org/10.1021/acsami.8b16487DOI Listing
December 2018

Cold atmospheric plasma and iron oxide-based magnetic nanoparticles for synergetic lung cancer therapy.

Free Radic Biol Med 2019 01 17;130:71-81. Epub 2018 Oct 17.

Department of pharmaceutics, Weifang Medical University, Weifang, Shandong 261053, China. Electronic address:

Cold atmospheric plasma (CAP) is an emerging biomedical technique that shows great potential for cancer treatment. On the other hand, magnetic nanoparticles open up a wide field of possible applications in medicine. Here we seek to develop a novel dual cancer therapeutic method by integrating promising CAP and iron oxide-based magnetic nanoparticles (MNPs), and evaluate its underlying mechanism for targeted lung cancer treatment. For this purpose, the synergistic effects of CAP and iron oxide-based MNPs on cellular bioactivity, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways were investigated. Results showed that the effectiveness of CAP and iron oxide-based MNPs for synergistic strongly killed activity against lung cancer cells, and significantly inhibited cell proliferation via reduction of viability and induction of apoptosis. Importantly, CAP combining with iron oxide-based MNPs induced EGFR downregulation while CAP inhibited lung cancer cells via depressing pERK and pAKT. Translation of these findings to an in vivo setting demonstrates that CAP combining iron oxide-based MNPs is effective at preventing xenograft tumors. Thus, the integration of CAP and iron oxide-based MNPs provides a promising tool for the development of a new cancer treatment strategy.
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http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.429DOI Listing
January 2019

Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing.

Int J Nanomedicine 2018 25;13:5771-5786. Epub 2018 Sep 25.

Department of Bioengineering, School of Bioscience and Technology, Weifang Medical University, Weifang 261053, Shandong, China,

Background: Nonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing.

Purpose: To overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated.

Methods: CMCS-OH30 NP were prepared by mild ionic gelation method and properties of the prepared CMCS-OH30 NP were determined by dynamic light scattering. Encapsulation efficiency, stability and release profile of OH30 from prepared CMCS-OH30 NP were determined by HPLC. Cytotoxicity, cell migration and cellular uptake of CMCS-OH30 NP were determined by conventional methods. The effects of prepared CMCS-OH30 NP on the wound healing was investigated by full-thickness excision animal models.

Results: The release of encapsulated OH30 from prepared CMCS-OH30 NP was maintained for at least 24 h in a controlled manner. CMCSOH30 NP enhanced the cell migration but had no effects on the metabolism and proliferation of keratinocytes. In the full-thickness excision animal models, the CMCS-OH30 NP treatment significantly accelerated the wound healing compared with CMCS or OH30 administration alone. Histopathological examination suggested that CMCS-OH30 NP promoted wound healing by enhancing the granulation tissue formation through the re-epithelialized and neovascularized composition. CMCS-OH30 NP induced a steady anti-inflammatory cytokine IL10 expression but downregulated the expressions of several pro-inflammatory cytokines.

Conclusion: The prepared biodegradable drug delivery system accelerates the healing and shows better prognosis because of the combined effects of OH30 released from the nanoparticles.
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http://dx.doi.org/10.2147/IJN.S156206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165789PMC
November 2018

Berberine Hydrochloride-Loaded Chitosan Nanoparticles Effectively Targets and Suppresses Human Nasopharyngeal Carcinoma.

J Biomed Nanotechnol 2018 Aug;14(8):1486-1495

Nasopharyngeal carcinoma (NPC) is a common epithelial malignancy that occurs in the nasopharynx and it is one of the high incidences of malignant tumors in China. As previous reports, berberine hydrochloride (BH) possesses a repressive effect on the proliferation of various cancer types. But the application of BH was hampered for a long time due to its hydrophobic properties, along with poor stability and bioavailability. In this study, folate acid modified chitosan nanoparticles loaded berberine hydrochloride (BH/FA-CTS NPs) were prepared by the ionic cross-linking technique, the physicochemical properties and the influence of BH/FA-CTS NPs on proliferation, migration and apoptosis in human nasopharyngeal carcinoma CNE-1 cells were studied in vitro and in vivo. Results of scanning electron microscopy (SEM) images showed that BH/FA-CTS NPs were sphere and the diameter was 258.2±9.1 nm. The drug loading and encapsulation efficiency were 8.17±1.12% and 87.73±4.21%, respectively. The drug release kinetics exhibited a slower and sustained release over a period of 48 h. Moreover, results of MTT assay and scratch assay displayed that BH/FA-CTS NPs inhibited proliferation and migration of CNE-1 cells remarkably. BH/FA-CTS NPs promoted apoptosis and necrosis of CNE-1 cells. And BH/FA-CTS NPs displayed distinguished higher tumor inhibition than control group, free BH and BH/CTS NPs in vivo. Therefore, as a nanocomposite, BH/FA-CTS NPs provide a new method and option for the treatment of nasopharyngeal carcinoma patients.
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http://dx.doi.org/10.1166/jbn.2018.2596DOI Listing
August 2018

Correlation between the Expression of PD-L1 and Clinicopathological Features in Patients with Thymic Epithelial Tumors.

Biomed Res Int 2018 23;2018:5830547. Epub 2018 Apr 23.

Department of Pathology, Weifang People's Hospital, Weifang, Shandong 261041, China.

The incidence of thymic epithelial tumors (TETs) in the Chinese population was much higher than that in the North American population. In clinical treatment, the prognosis of benign tumors after surgical resection was significantly better than that of malignant tumors. Currently, the commonly used clinical indicators for TET staging included Masaoka staging and WHO (2015) pathological criteria; however, the distinction between the benign and malignant tumors and diagnosis is yet to be explored. The current study demonstrated that the expression of PD-L1 in tumor cells was correlated with the degree of TET malignancy. The quantitative analysis of PD-L1 expression in 70 cases of TET tumor samples revealed that the positive rate of PD-L1 expression in types A, AB, B1, and B2 of thymoma (40 cases) was 37.5% (15/40), which was significantly lower than that in type B3 thymoma and thymic carcinoma (76.67%, 30 cases, 23/30) as demonstrated by chi-square test ( < 0.05). In addition, the two methods were analyzed for the quantitative detection of PD-L1 expression. The results from the estimation of transcriptional RNA expression and quantitative protein immunohistochemistry were consistent ( = 0.745). Furthermore, we also analyzed PD-L1 expression level in different types of TETs from TCGA database and observed that higher PD-L1 expression was in thymic carcinoma than in thymoma. Therefore, it could be concluded that PD-L1 expression in TET cells was correlated with the degree of malignancy, whereas the estimation of PD-L1 expression was potentially applicable in the clinical staging of TETs.
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http://dx.doi.org/10.1155/2018/5830547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937579PMC
October 2018

Intracellular endogenous glutathione detection and imaging by a simple and sensitive spectroscopic off-on probe.

Analyst 2018 May;143(10):2390-2396

Key Lab of Applied Pharmacology in Universities of Shandong, College of Pharmacy, Institute of Nanomedicine Research, Weifang Medical University, Weifang, 261053, China.

Glutathione (GSH) exhibits many cellular functions in human pathologies. A sensitive and simple method capable of assaying GSH would be useful to understand the mechanism of GSH-related diseases. In this study, a new colorimetric and fluorescent off-on probe, 3-oxo-3H-phenoxazin-7-ylthiophene-2-carboxylate, is constructed, synthesized and applied to determine fluctuations in intracellular GSH levels selectively and sensitively. The latent fluorescent probe is designed by reacting resorufin with thiophenecarboxylate and shows high sensitivity (LOD 8.9 × 10-7 M) and off-on fluorescent response to GSH over other different physiological species in pH 7.4 buffer solutions. A new reaction mechanism based on the cut-through of thiophenecarboxylate in the probe by GSH is confirmed via the HPLC (high performance liquid chromatography) and MS (mass spectrometry) analytical methods. Moreover, the probe is successfully applied to image GSH in A549 cells and indicates fluctuations in GSH levels under the stimulation of chemicals and drugs, which is verified by the investigation of the cell lysate with a commonly used commercial assay kit. As a result, it is feasible to monitor the levels of GSH in biosamples.
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http://dx.doi.org/10.1039/c8an00102bDOI Listing
May 2018

Protective effects of antioxidin-RL from Odorrana livida against ultraviolet B-irradiated skin photoaging.

Peptides 2018 03 16;101:124-134. Epub 2018 Jan 16.

School of Pharmacy, Weifang Medical University, Baotong Road, Weifang, 261053, Shandong, China. Electronic address:

The unavoidable daily exposure of the skin to ultraviolet (UV) B radiation is proven to have deleterious effects. The action mechanism of antioxidin-RL, an antioxidant peptide purified from skin secretions of frog Odorrana livida with amino acid sequence of AMRLTYNRPCIYAT, is well characterized by NMR titration and mutation based on ABTS scavenging activities. In order to explore the protective effects of antioxidin-RL against UVB-irradiated skin photoaging, cell uptake assay was used to detect the location of antioxidin-RL molecules serving various biological functions in the cells. The protective effects of antioxidin-RL on UVB-induced response were examined in vitro and in vivo. Results showed that antioxidin-RL successfully penetrated the cell membrane and exerted a positive effect on cell migration. It also effectively inhibited the UVB-induced excessive production of ROS and prevented oxidative damage to DNAs and proteins. Moreover, the mRNA expressions of MMP-1, VEGF, COX-2, and pro-inflammatory cytokines, such as IL-6 and TNF-α in antioxidin-RL-treated HaCaT and HSF cells were significantly down-regulated whereas those of FGF, procollagen type I and TGF-β1 up-regulated. Antioxidin-RL effectively prevented UVB-induced erythema on mouse skin, thereby inhibiting UVB-induced skin thickening and inflammation and increasing collagen deposition as demonstrated by in vivo experiments. Hence, the novel antioxidant peptide antioxidin-RL can effectively reduce UVB-induced skin reactions in vivo and in vitro, providing potential molecules against UVB-induced inflammation and photoaging.
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http://dx.doi.org/10.1016/j.peptides.2018.01.009DOI Listing
March 2018
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