Publications by authors named "Zhirong Zhang"

372 Publications

An exosome-mimicking membrane hybrid nanoplatform for targeted treatment toward Kras-mutant pancreatic carcinoma.

Biomater Sci 2021 Jul 12. Epub 2021 Jul 12.

Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610041, P. R. China.

Pancreatic carcinoma elevates quickly and thus has a high mortality rate. Therefore, early treatment is essential for treating pancreatic carcinoma. KRAS is the most frequently identified and one of the earliest mutations in pancreatic tumorigenesis. Thus, the KRAS-mutant cell is an ideal target for the treatment of pancreatic carcinoma, especially at the early stage. KRAS mutation increases macropinocytosis in pancreatic cancer cells, enhancing the internalization of exosomes. Because acquiring natural exosomes could be laborious and their encapsulation efficiency is often unsatisfactory, we aimed to develop a delivery system that mimics the Kras-mutant cell targeting capability of exosomes but is easier to generate and has better loading efficiency. For this purpose, we constructed a hybrid nanoplatform by fusing CLT (Celastrol)-Loaded PEGylated lipids with the DC2.4 cell membrane (M-LIP-CLT) to achieve targeted treatment of Kras-mutant pancreatic cancer. This hybrid nanoplatform improved CLT tumor accumulation and showed excellent anti-cancer efficiency both in vitro and in vivo with increased safety. These results suggest that M-LIP-CLT is an effective drug delivery system for targeted therapy against pancreatic carcinoma, and the fusion strategy showed attractive potential for further development.
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http://dx.doi.org/10.1039/d1bm00446hDOI Listing
July 2021

FABP5, a Novel Immune-Related mRNA Prognostic Marker and a Target of Immunotherapy for Multiple Myeloma.

Front Med (Lausanne) 2021 24;8:667525. Epub 2021 Jun 24.

Department of Hematology, The Second Affiliated Hospital of Shandong First Medical University, Taian, China.

Multiple myeloma is an incurable hematological malignancy. It is imperative to identify immune markers for early diagnosis and therapy. Here, this study analyzed immune-related mRNAs and assessed their prognostic value and therapeutic potential. Abnormally expressed immune-related mRNAs were screened between multiple myeloma and normal bone marrow specimens in the GSE47552 and GSE6477 datasets. Their biological functions were then explored. Survival analysis was presented for assessing prognosis-related mRNAs. CIBERSORT was utilized for identifying 22 immune cell compositions of each bone marrow specimen. Correlation between FABP5 mRNA and immune cells was then analyzed in multiple myeloma. Thirty-one immune-related mRNAs were abnormally expressed in multiple myeloma, which were primarily enriched in B cells-related biological processes and pathways. Following validation, FABP5 mRNA was a key risk factor of multiple myeloma. Patients with its up-regulation usually experienced unfavorable outcomes. There were distinct differences in the infiltration levels of B cells naïve, B cells memory, plasma cells, T cells CD4 naïve, resting memory CD4 T cells, activated memory CD4 T cells, Tregs, resting NK cells, M0 macrophages, M1 macrophages, M2 macrophages, and neutrophils between multiple myeloma and normal samples. FABP5 mRNA had correlations to B cells memory, B cells naïve, dendritic cells activated, macrophages M0, macrophages M1, macrophages M2, neutrophils, activated NK cells, resting memory CD4 T cells, CD8 T cells and Tregs. Collectively, our data showed that FABP5 mRNA was related to immune microenvironment, which could be a target of immunotherapy and prognostic marker for multiple myeloma.
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http://dx.doi.org/10.3389/fmed.2021.667525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266212PMC
June 2021

Bioinformatics Analysis of Choriocarcinoma-Related MicroRNA-Transcription Factor-Target Gene Regulatory Networks and Validation of Key miRNAs.

Onco Targets Ther 2021 29;14:3903-3919. Epub 2021 Jun 29.

Department of Gynaecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.

Objective: The aim of the current research was to construct a miRNA-transcription factor (TF)-target gene regulatory network in order to investigate the mechanism underlying choriocarcinoma and to verify the network through the overexpression or silencing of hub miRNAs in vitro.

Materials And Methods: A mRNA expression dataset and two miRNA expression datasets were analysed to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between normal cells and choriocarcinoma cells. The top 400 upregulated and downregulated DEGs were identified as candidate DEGs, which were then mapped to construct protein-protein interaction (PPI) networks and select hub genes. Moreover, the DGIdb database was utilized to select candidate drugs for hub genes. Moreover, DEM target genes were predicted through the miRWalk2.0 database and overlaid with candidate DEGs to identify the differentially expressed target genes (DETGs). Furthermore, we established miRNA-TF-target gene regulatory networks and performed functional enrichment analysis of hub DEMs. Finally, we transfected mimics or inhibitors of hub DEMs into choriocarcinoma cells and assessed cell proliferation and migration to verify the vital role of hub DEMs in choriocarcinoma.

Results: A total of 140 DEMs and 400 candidate DEGs were screened from choriocarcinoma cells and normal cells. A PPI network of 400 candidate DEGs was established. Twenty-nine hub genes and 99 associated small molecules were identified to provide potential target drugs for choriocarcinoma treatment. We obtained 70 DETGs of DEMs derived from the intersection between predicted miRNA target genes and candidate DEGs. Subsequently, 3 hub DEMs were selected, and miRNA-TF-target gene regulatory networks containing 4 TFs, 3 TFs and 3 TFs for each network were constructed. The RT-PCR results confirmed that miR-29b-3p was highly expressed and that miR-519c-3p and miR-520a-5p were expressed at low levels in choriocarcinoma cells. The overexpression or silencing results suggested that 3 dysregulated hub DEMs jointly accelerated the proliferation and migration of choriocarcinoma.

Conclusion: Association of miRNA-TF-target gene regulatory networks may help us explore the underlying mechanism and provide potential targets for the diagnosis and treatment of choriocarcinoma.
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http://dx.doi.org/10.2147/OTT.S311291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254590PMC
June 2021

Integrin αβ Targeting DGEA-Modified Liposomal Doxorubicin Enhances Antitumor Efficacy against Breast Cancer.

Mol Pharm 2021 Jul 16;18(7):2634-2646. Epub 2021 Jun 16.

Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, P.R. China.

Breast cancer was the leading cause of newly diagnosed cases of tumors in 2020, ranking as the second highest cause of female death. Chemotherapy remains the conventional treatment of choice for breast tumors in most clinical cases. However, it is often accompanied by a poor prognosis and severe side effects, resulting from an insufficient accumulation of the drug at tumor sites and an unsystematic distribution of the drug across the body. Inspired by the fact that breast tumor cells overexpress integrin αβ on the surface, we designed and constructed an integrin αβ targeting DGEA-modified liposomal doxorubicin (DGEA-Lipo-DOX) platform for application in breast cancer therapy. The DGEA-Lipo-DOX was stable with a uniform particle size of 121.1 ± 3.8 nm and satisfactory drug encapsulation. Demonstrated and , the constructed platform exhibited improved antitumor ability. The DGEA-Lipo-DOX showed 4-fold enhanced blood circulation and 6-fold increased accumulation of DOX at the tumor sites compared to those of free DOX, resulting in a significantly enhanced antitumor efficacy in tumor-bearing mice. A preliminary safety evaluation suggested that the systemic toxicity of DOX was relieved by DGEA-Lipo delivery. Collectively, binding integrin αβ by DGEA may represent an alternative therapeutic strategy for potentially safer breast cancer treatment.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00132DOI Listing
July 2021

Novel brain-targeting 3-n-butylphthalide prodrugs for ischemic stroke treatment.

J Control Release 2021 Jul 1;335:498-514. Epub 2021 Jun 1.

West China School of Pharmacy, College of Polymer Science and Engineering, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Sichuan University, Chengdu 610064, PR China. Electronic address:

Currently, ischemic stroke is the leading cause of disability and death worldwide, and the performance of corresponding drugs is often unsatisfactory owing to the complex pathological processes and the impediment of the blood-brain barrier (BBB). Here, we employed various tertiary amino groups, including different linear, cyclic, and bimolecular drug structures, to modify 3-n-butylphthalide (NBP), a natural product used for ischemic stroke treatment, which has poor bioavailability, to generate a series of six prodrugs. These prodrugs showed significantly improved solubility and cellular uptake, which were primarily driven by putative pyrilamine cationic transporters. They also displayed more efficient brain delivery in vivo, reaching as high as 21.5-fold brain accumulation increase compared with NBP, leading to much higher bioavailability and stronger therapeutic effects. The toxicity of these molecules is also lower or similar to that of unmodified NBP. We showed that the tertiary amino group-modified NBP prodrugs are effective and safe for treating ischemic stroke with significantly enhanced druggability; hence, they have potential for further clinical development.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.045DOI Listing
July 2021

Redox-responsive nanoassembly restrained myeloid-derived suppressor cells recruitment through autophagy-involved lactate dehydrogenase A silencing for enhanced cancer immunochemotherapy.

J Control Release 2021 Jul 26;335:557-574. Epub 2021 May 26.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address:

Myeloid-derived suppressor cells (MDSCs) are the chief accomplices for assisting tumor's survival and suppressing anti-tumor immunity, which can be recruited by tumor-derived cytokines, such as granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). The plentiful lactate dehydrogenase A (LDHA) in glycolysis is usually accompanied by abundant tumor-derived G-CSF and GM-CSF, further promoting MDSCs recruitment and immunosuppression. Herein, with the aim to achieve powerful anti-tumor immunity, an immunochemotherapy regimen basing on a redox-responsive nanoassembly (R-mPDV/PDV/DOX/siL) is developed, which integrates the combined strategy of restraining cytokines-mediated MDSCs recruitment through LDHA silencing and reinforcing tumor immunogenicity through anthracycline (DOX)-elicited immunogenic cell death (ICD) effects. This redox-responsive nanoassembly is self-assembled by three glutathione (GSH)-responsive polymers, which employ poly(δ-valerolactone) (PVL) as hydrophobic segment and 3, 3'-dithiodipropionic acid (DA) as linkage to connect hydrophilic segment. DOX is encapsulated in the core and LDHA siRNA (siL) is effectively compressed by cationic PAMAM. The cellular internalization and tumor-homing are strengthened by the specific recognition on integrin (αβ) by c(RGDfk) (RGD) ligand. After escaping from endosomes/lysosomes, R-mPDV/PDV/DOX/siL is disintegrated through GSH-elicited cleavage of DA, realizing burst release of drugs and high-efficient LDHA silencing. The reduced expression of LDHA suppresses the generation of G-CSF and GM-CSF cytokines, restrains MDSCs recruitment and reinforces anti-tumor immunity. Eventually, this therapeutic regimen of DOX and siL on R-mPDV/PDV/DOX/siL nanoassembly achieved powerful anti-tumor efficiency on 4 T1 orthotopic tumor, opening the new horizons for immunochemotherapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.034DOI Listing
July 2021

Self-promoted Albumin-Based Nanoparticles for Combination Therapy against Metastatic Breast Cancer via a Hyperthermia-Induced "Platelet Bridge".

ACS Appl Mater Interfaces 2021 Jun 27;13(22):25701-25714. Epub 2021 May 27.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.

It has been a great challenge to simultaneously inhibit the outgrowth of both the primary tumor and metastasis in metastatic cancer treatment. Substantial studies have evidenced that the interaction of platelets and cancer cells supports tumor metastasis, and platelets are considered to have metastasis-targeting property. Inspired by injury-targeting and metastasis-targeting properties of platelets, we constructed a photothermal therapy strategy with activated platelet-targeting albumin-based nanoparticles, PSN-HSA-PTX-IR780, to amplify drug delivery in the primary tumor at mild temperatures and simultaneously inhibit metastasis via a "platelet bridge". Human serum albumin (HSA) was premodified with a P-selectin-targeting peptide (PSN peptide) or IR780 serving as a photosensitizer. Hybrid albumin nanoparticles were assembled via the disulfide reprogramming method and encapsulated paclitaxel (PTX) to formulate PSN-HSA-PTX-IR780. The PSN-modified albumin nanoparticles could bind with upregulated P-selectin on activated platelets and subsequently target cancer cells by using platelets as a "bridge". In addition, nanoparticle-generated hyperthermia induced tissue injury and increased tumor-infiltrating platelets, thereby recruiting more nanoparticles into the tumor in a self-promoted way. studies showed that the drug accumulation of PSN-HSA-PTX-IR780 was 2.86-fold higher than that of HSA-PTX-IR780 at the optimal temperature (45 °C), which consequently improved the therapeutic outcome. Moreover, PSN-HSA-PTX-IR780 also effectively targets and inhibits lung metastasis by binding with metastasis-infiltrating platelets. Altogether, the self-promoted nanoplatform provides a unique and promising strategy for metastatic cancer treatment with enhanced drug delivery efficacy.
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http://dx.doi.org/10.1021/acsami.1c04442DOI Listing
June 2021

Association Between Gut and Metabolic Syndrome is Dose-Dependent and Affected by Microbial Interactions: A Cross-Sectional Study.

Diabetes Metab Syndr Obes 2021 17;14:2177-2188. Epub 2021 May 17.

The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Objective: is among the most abundant bacterial species in the human intestine; however, its relationship to metabolic syndrome (MetS)-which is linked to gut dysbiosis-is not known. In this study, we investigated the association between abundance and risk of MetS and its components, as well as dose-response effects and the influence of microbial interactions on the association.

Methods: This cross-sectional study included 6896 Chinese participants aged 18 to 97 years from the Guangdong Gut Microbiome Project. MetS was defined according to Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults criteria. The abundance of was assessed by 16S rRNA sequencing. Logistic regression analysis with adjustment for common confounders was performed to evaluate the association between and MetS and its components. Models with restricted cubic splines and interaction terms were used to examine the dose-response association and microbial interactions, respectively.

Results: The prevalence of MetS was 20.4%, and the median abundance of was 0.08% (interquartile range: 0.04-0.93%). Increased abundance was associated with decreased risk of MetS ( <0.05), but this effect was not observed until the level was 0.2% of the total gut microbiota abundance (odds ratio=0.96, 95% confidence interval: 0.94-0.98). Of the 5 MetS components, obesity and hypertriglyceridemia showed the strongest association with , followed by reduced high-density lipoprotein cholesterol, hypertension, and hyperglycemia. Microbial interaction analyses showed that Ruminococcaceae and Lachnospiraceae were the predominant bacterial families and were not only correlated with abundance but also influenced the -MetS association.

Conclusion: There is a dose-response association between reduced risk of MetS and increased abundance of . The association between and 5 MetS components is variable and affected by microbial interactions.
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http://dx.doi.org/10.2147/DMSO.S311388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139944PMC
May 2021

Phenylboronic acid modified nanoparticles simultaneously target pancreatic cancer and its metastasis and alleviate immunosuppression.

Eur J Pharm Biopharm 2021 Aug 19;165:164-173. Epub 2021 May 19.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

Pancreatic ductal adenocarcinoma is one of the most lethal malignant tumors, its drug resistance, immunosuppression and metastasis makes the traditional chemotherapy and immunotherapy inefficient. Here we confirmed a 3-aminophenylboronic acid-modified low molecular weight heparin-D-α-tocopheryl succinate micellar nanoparticle (PBA-LMWH-TOS NP, PLT NP) could inhibit orthotopic pancreatic tumor and its spontaneous metastases. The small particle size and high affinity of PBA to sialic acid residue (SA) made PLT/PTX NPs significantly targeted and accumulated in both pancreatic tumor tissues and metastases. The immunosuppressive microenvironment of pancreatic tumor was most caused by the infiltration of immunosuppressive cells, mainly myeloid-derived suppressor cells (MDSCs). We first reported that P-selectin glycoprotein ligand-1 (PSGL-1) was expressed on the surfaces of MDSCs in pancreatic tumor tissues. Meanwhile, we found that LMWH could inhibit the early stage of adhesion cascade between vascular endothelial cells (VECs) and MDSCs by interfering with P-selectin/PSGL-1 binding, thus inhibiting MDSC recruitment to pancreatic tumor tissues. The therapeutic results indicated that PLT/PTX NPs could significantly improve the immune microenvironment of pancreatic tumor and inhibit spontaneous metastases. This nanosystem provides a new immune microenvironment regulation mechanism based on carrier materials in pancreatic tumor, and has high clinical application potential.
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http://dx.doi.org/10.1016/j.ejpb.2021.05.014DOI Listing
August 2021

Generated High-Valent Iron Single-Atom Catalyst for Efficient Oxygen Evolution.

Nano Lett 2021 Jun 21;21(11):4795-4801. Epub 2021 May 21.

Hefei National Laboratory for Physical Sciences at the Microscale, Key Laboratory of Strongly-Coupled Quantum Matter Physics of Chinese Academy of Sciences, National Synchrotron Radiation Laboratory, Key Laboratory of Surface and Interface Chemistry and Energy Catalysis of Anhui Higher Education Institutes, Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

Oxygen evolution reaction (OER) plays an important role in renewable energy supplies as the anodic reaction for electrochemical transformation of various chemicals. Iron-based OER catalysts are potential candidates due to their abundance but suffer from poor activity. Here we demonstrate that a single-atom iron catalyst with - generated Fe centers is highly active toward OER. Only an overpotential of 320 mV was needed to reach 10 mA cm. The catalyst exhibited an ultrahigh turnover frequency of 0.62 s at an overpotential of 0.35 V, which is comparable to currently reported transitional-metal based OER catalysts. Experimental and theoretical studies revealed that the valence state of the metal center transferred from Fe to highly active Fe prior to the OER process. This transformation was originated from the strong interaction between atomic Fe and carbon support via C-O-Fe bonding, leading to a lower energy barrier of the rate-limiting *OOH formation.
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http://dx.doi.org/10.1021/acs.nanolett.1c01335DOI Listing
June 2021

A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression.

Cell Rep 2021 May;35(7):109129

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France; Centre National de la Recherche Scientifique UMR 7104, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale U964, Strasbourg, France; Université de Strasbourg, Strasbourg, France. Electronic address:

Mitochondria are highly dynamic organelles subjected to fission and fusion events. During mitosis, mitochondrial fission ensures equal distribution of mitochondria to daughter cells. If and how this process can actively drive mitotic progression remains largely unknown. Here, we discover a pathway linking mitochondrial fission to mitotic progression in mammalian cells. The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells. Phosphorylation of MFF is crucial for chromosome segregation and promotes cell survival by inhibiting adaptation of the mitotic checkpoint. Thus, PKD/MFF-dependent mitochondrial fission is critical for the maintenance of genome integrity during cell division.
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http://dx.doi.org/10.1016/j.celrep.2021.109129DOI Listing
May 2021

Mild hyperthermia promotes immune checkpoint blockade-based immunotherapy against metastatic pancreatic cancer using size-adjustable nanoparticles.

Acta Biomater 2021 May 14. Epub 2021 May 14.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, P.R. China. Electronic address:

Immune checkpoint blockade treatment is one of the most promising immunotherapies, which exhibits promising therapeutic effects on inhibition of metastasis. However, immunotherapy has little effect on pancreatic cancer, due to its extensive fibrotic matrix and immunosuppressive tumor microenvironment. Mild hyperthermia induced by photothermal therapy (PTT) has been proven to activate the immune responses in the tumor microenvironment. Herein, we designed a combine strategy of mild hyperthermia and immune checkpoint blockade (BMS-202) treatment with size-adjustable thermo- and fibrotic matrix- sensitive liposomes ([email protected]), in which BMS-202 loaded small-sized albumin nanoparticle (HSA-BMS) was encapsulated. Mild hyperthermia reduced the tumor hypoxia, relieved the interstitial pressure and increased the recruitment of endogenous immune cells in tumors. In the meantime, small-sized HSA-BMS was released from large-sized [email protected] in response to fibroblast activation protein-α (FAP-α) and near-infrared (NIR) laser, and enhanced the immunological responses by recovering the activity of T lymphocytes, accompanied by secreting relevant cytokines (TNF-α and IFN-γ). The combined therapy ([email protected]) could not only significantly suppress the tumor growth in vivo, but also decrease the amounts of metastatic nodules in distant organs. These results suggested that size-adjustable nanoparticles had a great potential in the treatment of metastatic pancreatic cancer. STATEMENT OF SIGNIFICANCE: The desmoplastic stroma and hypoperfusion of pancreatic cancer imposed physical barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. We constructed size-adjustable thermo- and fibrotic matrix- sensitive liposomes ([email protected]) with size around 120 nm, where small sized albumin nanoparticle (10 nm) of immune checkpoint inhibitor (HSA-BMS) were encapsulated inside. Mild hyperthermia not only contributed to release HSA-BMS for penetration (blocking the immunosuppressive signals deep in the tumor), but enhanced tumor blood perfusion for infiltration of endogenous immune cells. In the two-pronged treatment, the pancreatic cancer immunotherapy significantly enhanced and the risk of cancer metastasis was reduced. Overall, the strategy provides a promising approach to increase drug accumulation and improve the anti-tumor immune activity in pancreatic cancer.
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http://dx.doi.org/10.1016/j.actbio.2021.05.002DOI Listing
May 2021

Associated Factors of Suboptimal Health Status Among Adolescents in China: A Cross-Sectional Study.

J Multidiscip Healthc 2021 7;14:1063-1071. Epub 2021 May 7.

Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.

Purpose: Suboptimal health status (SHS) is a state between health and disease, has several adverse effects, although, its main underlying mechanism is still unclear. This study aimed to investigate SHS and its associated factors of adolescents.

Methods: A community-based cross-sectional study was conducted in the three different geographic locations of China (Shanxi, Guangzhou, and Tibet). A multidimensional sub-health questionnaire of adolescent (MSQA) is used to evaluate SHS. Independent two-sample K-S test was performed for the quantitative data as the non-parametric test, whereas Chi-square test method was applied to explore the difference of discrete variables data between groups. Then finally, multiple logistic regression analysis was applied to analyze the influential factors of SHS.

Results: Among 1461 respondents (between 15 and 18 years old), females proportion (56.47%) was higher than males (43.53%) where SHS was higher in Shanxi followed by Tibet and then Guangdong. The rural area, grade, lack of sleep time, home visit in a week, lack of exercise, a heavy burden of study, smoking, drinking, and fewer friends were the risk factors of SHS, while families living status, seeking help and extroversion were the protective factors.

Conclusion: SHS is significantly associated with behavior and lifestyle-related factors. For comprehensively prevention and control of the SHS, it is urgently needed to reduce the risk factors and enhance the protective factors among adolescents.
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http://dx.doi.org/10.2147/JMDH.S302826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114174PMC
May 2021

Shield and sword nano-soldiers ameliorate rheumatoid arthritis by multi-stage manipulation of neutrophils.

J Control Release 2021 Jul 7;335:38-48. Epub 2021 May 7.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

Rheumatoid arthritis (RA) is characterized by the outbreak of inflammation. Neutrophils, the main culprit of the outbreak of inflammation, are the first inflammatory cells to be recruited to inflamed joints and facilitate the recruitment of themselves by stimulating the release of chemokines. Here, based on neutrophils, a novel anti-inflammatory "shield and sword soldiers" strategy is established with LMWH-TOS nanoparticles (LT NPs). The hydrophilic fragment low molecular weight heparin (LMWH) acts as a shield which block the transvascular movement of neutrophils through inhibiting the adhesion cascade by binding to P-selectin on inflamed endothelium. Synergistically, MMP-9, which is secreted by the recruited neutrophils and degrade the main component of articular cartilage, is reduced by the hydrophobic fragment d-α-tocopheryl succinate (TOS), functioning as a sword. In collagen-induced arthritis (CIA) mouse model, LT NPs show significant targeting effect, and exhibit prominent therapeutic efficacy after enveloping the first-line anti-RA drug methotrexate. Our work proves that the multi-stage manipulation of neutrophils is feasible and effective, providing a new concept for RA treatment.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.008DOI Listing
July 2021

Hostile Interactions of Punjab Urial () towards Indian Gazelle () during Feeding Sessions in Captive Breeding Settings.

Animals (Basel) 2021 Apr 28;11(5). Epub 2021 Apr 28.

College of Wildlife and Protected Areas, Northeast Forestry University, Harbin 150040, China.

Natural wildlife habitats are regularly subjected to anthropogenic pressures for different purposes, which are heading the biodiversity towards drastic decline. Several endangered wild species are raised in captivity with the aim of re-introduction. In some instances, mixed herds' rearing approach in captivity is adopted for providing social enrichment to captive stocks; however, the impacts of species on each other are least documented. We tested our prediction that keeping mixed herds of captive wild sheep and antelopes provides adequate social enrichment to the captive stocks: if interspecific interactions are balanced. In the current study, we studied the interspecific competition between mixed herds of captive Punjab urial () and Indian gazelle () at Manglot Wildlife Park, Nowshera District, Khyber Pakhtunkhwa Province, Pakistan. We documented the negative effects of behavioural interference by Punjab urial on the feeding behaviour of Indian gazelle. The outcome of the current study revealed that Punjab urial are highly intolerant towards Indian gazelle, with high interference during feeding. Out of the total aggressive events, 77% ( = 1259) of events ended up with win/loss, in which Punjab urial dominated the Indian gazelle 3.5 times. Moreover, lopsided dominance by Punjab urial resulted in increased intraspecific competition among Indian gazelle ( < 0.001). Current study divulged Indian gazelle to be the subordinate species, with less intake of food. Instead of providing social enrichment by heterospecifics, the Punjab urial is negatively affecting the Indian gazelle, therefore, the results of our study discourage the practice of admix captive breeding for wild sheep and antelopes.
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http://dx.doi.org/10.3390/ani11051274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145856PMC
April 2021

Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis.

Nat Commun 2021 04 12;12(1):2174. Epub 2021 Apr 12.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610064, China.

Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvβ3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.
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http://dx.doi.org/10.1038/s41467-021-22454-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042091PMC
April 2021

pH-Triggered Copper-Free Click Reaction-Mediated Micelle Aggregation for Enhanced Tumor Retention and Elevated Immuno-Chemotherapy against Melanoma.

ACS Appl Mater Interfaces 2021 Apr 9;13(15):18033-18046. Epub 2021 Apr 9.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.

Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno-chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-β (TGF-β)/Smad3 signaling pathway inhibitor SIS3. Polycaprolactone-poly(ethylene glycol) (PCL-PEG) micelles modified with dibenzylcyclooctyne (DBCO) or azido (N) and coated with acid-cleavable PEG were established. This nanoplatform, namely, [email protected]/SIS3, could remain well dispersed in the neutral systemic circulation, while quickly respond to the acidic tumor microenvironment and intracellular lysosomes, triggering copper-free click reaction-mediated aggregation, leading to the increased tumor accumulation and reduced cellular efflux. In addition, the combination of DOX with SIS3 facilitated by the aggregation strategy resulted in potent inhibition of melanoma tumor growth and significantly increased NK cells, NK cell cytokines, and antitumor T cells in the tumor. Taken together, our study offered a new concept of applying copper-free click chemistry to achieve nanoparticle aggregation and enhance tumor retention, as well as a promising new combined tumor treatment approach of chemotherapy and immunotherapy.
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http://dx.doi.org/10.1021/acsami.1c02567DOI Listing
April 2021

Efficacy of Sanqi (Radix Notoginseng) in treating cerebral hemorrhage in rats with traumatic brain injury.

J Tradit Chin Med 2021 04;41(2):262-269

Department of Intensive Care Unit, the First Affiliated Rehabilitation Hospital of Zhejiang Chinese Medical University (the First Affiliated Hospital, Zhejiang Chinese Medical University), Hangzhou 310023, China.

Objective: To evaluate the protective efficacy of Sanqi (Radix Notoginseng) on cerebral hemorrhage in a rat model of traumatic brain injury (TBI) by investigating plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA), nuclear factor-κB (NF-κB, p-p65), nitric oxide (NO), endothelin (ET), cluster differentiation (CD61CD62), and coagulation.

Methods: The free-fall method was used to create a rat model of TBI. Forty-eight rats were randomly divided into six groups: the blank group, sham group, model group, low-dose Sanqi (Radix Notoginseng) group, middle-dose Sanqi (Radix Notoginseng) group, and high-dose Sanqi (Radix Notoginseng) group. At 24 h after the model was created, we investigated brain MRI, brain tissue morphology using HE staining, flow cytometry, and immunohistochemical changes.

Results: Cerebral hemorrhage was aggravated in TBI rats (observed in brain specimens, brain MRI, and brain tissue HE). Cerebral immunohistochemistry results demonstrated that the expression of t-PA, PAI-1 and p-p65 increased significantly in TBI rats, while t-PA/PAI-1 had a significant decrease. In addition, CD61CD62, D2D, and ET were significantly increased in TBI rats, and PT and APTT were significantly prolonged; in contrast, NO was significantly decreased. Sanqi (Radix Notoginseng) decreased cerebral hemorrhage in TBI rats (observed in brain MRI and brain tissue HE), and increased t-PA/PAI-1, CD61CD62 significantly. It also significantly decreased the expression of t-PA, PAI-1, and p-p65 in brain immunohistochemistry and significantly decreased PT, APTT, D2D, and ET. However, there were no differences in NO between the model group and the Sanqi (Radix Notoginseng) group.

Conclusion: Sanqi (Radix Notoginseng) can decrease the expression of p-p65, increase t-PA/PAI-1, and stem traumatic intracranial hemorrhage in a TBI rat model.
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April 2021

Engineering a sustained release vaccine with a pathogen-mimicking manner for robust and durable immune responses.

J Control Release 2021 05 29;333:162-175. Epub 2021 Mar 29.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address:

Sustained release vaccine carriers can facilitate an increased interaction time between the antigen and immune system to strengthen immune responses, but their promotion on adaptive immune responses, especially cellular immunity, are still unfavorable. Herein, we report a sustained antigen delivery vector, which carries abundant antigens, a nucleic acid adjuvant and pathogen-associated molecular patterns to simulate a natural pathogen to reinforce immune responses. Specifically, murine colorectal cancer cells MC38 lysate and Toll-like receptor 9 agonist CpG are loaded into yeast derived β-glucan particles (GPs). After vaccination, these particles can form a vaccine depot that continuously release the antigen similar to the traditional aluminum hydroxide gel, but recruit more immune cells and induce more cytokine secretion at the injection site. Stronger antibody responses, Th1 and Th17 biased cellular immunity and immune memory are achieved compared with aluminum hydroxide gel. More importantly, treatment with these particles significantly suppress tumor growth in a therapeutic tumor model. This work shed light on the efficacy of combining sustained antigen release with pathogen-mimicking manner in vaccine design.
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http://dx.doi.org/10.1016/j.jconrel.2021.03.037DOI Listing
May 2021

Identification of an Intermediate Form of Ferredoxin That Binds Only Iron Suggests That Conversion to Holo-Ferredoxin Is Independent of the ISC System in Escherichia coli.

Appl Environ Microbiol 2021 04 27;87(10). Epub 2021 Apr 27.

Laboratory of Molecular Medicine, Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine (Ministry of Education, China), School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China

[2Fe-2S]-ferredoxin and other ISC proteins encoded by the () operon are responsible for the assembly of iron-sulfur clusters. It is proposed that ferredoxin (Fdx) donates electrons from its reduced [2Fe-2S] center to iron-sulfur cluster biogenesis reactions. However, the underlying mechanisms of the [2Fe-2S] cluster assembly in Fdx remain elusive. Here, we report that Fdx preferentially binds iron, but not the [2Fe-2S] cluster, under cold stress conditions (≤16°C). The iron binding in Fdx is characterized by a unique absorption peak at 320 nm based on UV-visible spectroscopy. In addition, the iron-binding form of Fdx could be converted to the [2Fe-2S] cluster-bound form after transferring cold-stressed cells to normal cultivation temperatures above 25°C. experiments also revealed that Fdx could utilize bound iron to assemble the [2Fe-2S] cluster by itself. Furthermore, inactivation of the genes encoding IscS, IscU, and IscA did not limit [2Fe-2S] cluster assembly in Fdx, which was also observed by inactivating the or operon, indicating that iron-sulfur cluster biogenesis in Fdx arose from a unique pathway in Our results suggest that the intracellular assembly of [2Fe-2S] clusters in Fdx is susceptible to environmental temperatures. The iron binding form of Fdx (Fe-Fdx) is a precursor during its maturation to a cluster binding form ([2Fe-2S]-Fdx), and reassembly of the [2Fe-2S] clusters during temperature increases is not strictly reliant on other specific iron donors and scaffold proteins within the Isc or Suf system. Fdx is an electron carrier that is required for the maturation of many other iron-sulfur proteins. Its function strictly depends on its [2Fe-2S] center that bonds with the cysteinyl S atoms of four cysteine residues within Fdx. However, the assembly mechanism of the [2Fe-2S] clusters in Fdx remains controversial. This study reports that Fdx fails to form its [2Fe-2S] cluster under cold stress conditions but instead binds a single Fe atom at the cluster binding site. Moreover, when temperatures increase, Fdx can assemble clusters by itself from its iron-only binding form in cells. The possibility remains that Fdx can effectively accept clusters from multiple sources. Nevertheless, our results suggest that Fdx has a strong iron binding activity that contributes to the assembly of its own [2Fe-2S] cluster and that Fdx acts as a temperature sensor to regulate Isc system-mediated iron-sulfur cluster biogenesis.
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http://dx.doi.org/10.1128/AEM.03153-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117754PMC
April 2021

Nanoemulsions Target to Ectopic Lymphoids in Inflamed Joints to Restore Immune Tolerance in Rheumatoid Arthritis.

Nano Lett 2021 03 9;21(6):2551-2561. Epub 2021 Mar 9.

Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, P.R. China.

Inducing immune tolerance through repeated administration of self-antigens is a promising strategy for treating rheumatoid arthritis (RA), and current research indicates that coadministration of immunomodulators can further orchestrate the tolerogenic response. However, most of the clinical trials based on tolerance induction have negligible therapeutic effects. Peripheral lymphoid organs play critical roles in immunotherapy. Here, we design an engineered nanoemulsion for targeted codelivery of self-antigens and an immunomodulator to ectopic lymphoid structures (ELSs) in inflamed joints of RA. Namely, a citrullinated multiepitope self-antigen (CitP) and rapamycin are incorporated into the nanoemulsions ([email protected]/Rapa), which are fabricated by a facial method using commercialized pharmaceutical excipients. After intravenous administration, the nanoemulsion shows satisfactory accumulation in the inflamed paws and provides enhanced anti-inflammatory effect in various experimental murine models of RA. Our study provides a promising targeting strategy to induce immune tolerance for the treatment of RA.
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http://dx.doi.org/10.1021/acs.nanolett.0c05110DOI Listing
March 2021

Three-dimensional reconstruction model in the diagnosis of Morgagni's hernia.

BMJ Case Rep 2021 Feb 8;14(2). Epub 2021 Feb 8.

Department of Thoracic surgery, Beijing Chao-Yang Hospital, Beijing, China.

Morgagni's hernia (MH) can be diagnosed by different utilities, but all these methods are not always 100% accurate. Three-dimensional (3D) reconstruction model could be helpful in better understanding the important anatomical structures. We report a case of MH who was once misdiagnosed as diaphragmatic eventration at the other institution and we offered laparoscopic repair according to the 3D reconstruction model. Our case highlights that 3D reconstruction model could be a useful supplementary tool in the diagnosis and preoperative assessment for patients with MH especially when it is confused in diagnosis in clinical practice.
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http://dx.doi.org/10.1136/bcr-2020-239911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872911PMC
February 2021

Comparative Analyses of Chloroplast Genomes From 14 Species: Identification of Variable DNA Markers and Phylogenetic Relationships Within the Genus.

Front Plant Sci 2020 13;11:605793. Epub 2021 Jan 13.

TAAHC-SWU Medicinal Plant Joint R&D Center, Tibetan Collaborative Innovation Center of Agricultural and Animal Husbandry Resources, Food Science College, Tibet Agriculture and Animal Husbandry University, Nyingchi, China.

L. is an economic crop with a long history of cultivation and domestication and has important economic, ecological, and medicinal value. To solve the classification problems caused by the similar morphological characteristics of and establish a credible phylogenetic relationship, we sequenced and annotated six chloroplast (cp) genomes (, and ) and combined them with previously published genomes for the species. We used bioinformatics methods to analyze the genomic characteristics, contraction, and expansion of inverted repeat (IR) regions; differences in simple sequence repeats (SSRs) and long repeat sequences; species pairwise Ka/Ks ratios; divergence hotspots; and phylogenetic relationships of the 14 species. The results revealed that cp genomes of range in size from 158,071 to 158,963 bp and contain 87 protein-coding, 37 tRNA, and 8 rRNA genes. Seven mutational hotspots were identified as candidate DNA barcode sequences to distinguish species. The phylogenetic analysis strongly supported the genus as a subgenus of and proposed the possibility of a new subgenus in The availability of these genomes will provide valuable information for identifying species, molecular breeding, and evolutionary analysis of
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http://dx.doi.org/10.3389/fpls.2020.605793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838127PMC
January 2021

Complete mitochondrial genome of the spotted nutcracker (Passeriformes: Corvidae) from Shan'xi Province, China.

Mitochondrial DNA B Resour 2020 Jun 16;5(3):2456-2457. Epub 2020 Jun 16.

College of Wildlife and Protected Area, Northeast Forestry University, Harbin, P. R. China.

We determined the whole mtDNA genome of the Spotted Nutcracker () in Tianlong Mountain, Shan'xi Province, China. The complete mitochondrial genome is 16,914 bp in length and consists of 13 protein-coding genes (PCGS), 22 genes, 2 genes, and 1 control region (D-loops). The nucleotide composition is 25.08% A, 25.08% T, 24.75% G, and 25.08% C. The result of phylogenetic analysis showed that there was close genetic relationship between and . It is expected that the complete mitochondrial genome presented here will contribute to the analysis of species distribution.
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http://dx.doi.org/10.1080/23802359.2020.1778565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782841PMC
June 2020

The complete mitochondrial genome of the (Passeriformes: Sittidae) from China.

Mitochondrial DNA B Resour 2020 Jun 5;5(3):2328-2329. Epub 2020 Jun 5.

College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.

We describe the whole mtDNA genome of the Chinese nuthatch in Tianlong Mountain, Shanxi, China. It is actually a circular molecular of 16,816 bp in length and consists 13 protein-coding genes, 22 transfer-RNA genes, 2 ribosomal-RNA genes, and 1 control region (D-loop, 1,243 bp in length). The nucleotide composition is 30.3% A, 30.1% C, 14.5% G, 25.1% T. The phylogenetic analysis based on the maximum likelihood method revealed the relationship of was close to the three reported species within the same genus , which are , and .
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http://dx.doi.org/10.1080/23802359.2020.1773341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782314PMC
June 2020

The complete mitochondrial genome of water deer in Liaoning, China.

Mitochondrial DNA B Resour 2020 Jan 29;5(1):922-923. Epub 2020 Jan 29.

College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.

We determined the whole mtDNA genome of the water deer ( in Benxi, Liaoning. The total length of the complete mitochondrial genome is 16,355 bp and it consists of 13 protein-coding, 22 tRNA, rRNA genes, and 1 control region (CR). Two overlaps among the 13 protein-coding genes were found: ND4L/ND4 and ND5/ND6. The CR is 928 bp in length. The nucleotide composition is 30.52% A, % 33.38 T, 22.77% G, and 13.32% C.
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http://dx.doi.org/10.1080/23802359.2020.1719936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748434PMC
January 2020

A "dual-guide" bioinspired drug delivery strategy of a macrophage-based carrier against postoperative triple-negative breast cancer recurrence.

J Control Release 2021 01 27;329:191-204. Epub 2020 Nov 27.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China. Electronic address:

Recurrence after tumor resection is mainly caused by post-operative inflammation and residual cancer cells, which is a serious obstacle to breast cancer treatment. Traditional nanoparticles rely primarily on the enhanced permeability and retention (EPR) effect in well-vascularized tumors. In this study, a macrophage-based carrier is designed to enhance the efficiency of targeting to recurrent tumors through a "dual-guide" strategy. After tumor resection, a burst of inflammatory factors occurs in the resection wound, which can recruit monocytes/macrophages rapidly. Combined with the tropism of monocyte chemoattractant protein, a large number of macrophage-mediated carriers will be recruited to surgical recurrence sites. Octaarginine (RRRRRRRR, R8)-modified liposomes in macrophages contain two agents with different pharmacological mechanisms, paclitaxel (PTX) and resveratrol (Res), which have enhanced therapeutic effects. In vitro study demonstrated that macrophage-mediated carriers approach 4 T1 cells through an inflammatory gradient and reach recurrence tumors through a "dual-guide" strategy. Then, membrane fusion and inflammation-triggered release deliver the drug into the recurrent tumor cells. In vivo experiments show that macrophage-based carriers exhibit effective tumor-targeting ability, especially in post-operation situations. More importantly, macrophage-mediated liposomes encapsulated with PTX and Res inhibit tumor recurrence in both ectopic and orthotopic 4 T1 post-operative recurrence models.
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http://dx.doi.org/10.1016/j.jconrel.2020.11.039DOI Listing
January 2021

Lobe-specific Lymph Node Dissection in Clinical Stage IA Solid-dominant Non-small-cell Lung Cancer: A Propensity Score Matching Study.

Clin Lung Cancer 2021 03 15;22(2):e201-e210. Epub 2020 Oct 15.

Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Lobectomy with systematic lymph node dissection (SND) remains the standard procedure for resectable non-small-cell lung cancer (NSCLC), whereas lobe-specific lymph node dissection (LSND) was reported to have more advantages in perioperative recovery and complication reduction in treating early-stage diseases. Survival outcomes after LSND remains controversial compared with SND.

Patients And Methods: From 2014 to 2017, data of 546 patients with clinical stage IA solid-dominant NSCLC and who underwent curative lobectomies with LSND (n = 100) or SND (n = 446) at our institution were collected. Propensity score matching was conducted to eliminate the biases. Five-year disease-free survival and overall survival were compared between the groups. Perioperative parameters and postoperative complications were also analyzed.

Results: Lobectomies with LSND or SND were performed in 100 patients and 446 patients, respectively. After matching, there were 100 patients in each group and no significant differences in 5-year overall survival (P = .473) and disease-free survival (P = .789) were found between the groups. Recurrence patterns were also similar (P = .733). Perioperative parameters were similar, whereas the incidence of postoperative complications in the SND group was found to be significantly higher than that in the LSND group (P = .003).

Conclusions: Our study demonstrated that LSND has similar efficiency to SND in terms of survival, recurrence, lymph node dissection, and perioperative recovery of patients with clinical stage IA solid-dominant NSCLC, as well as significant advantages in reducing postoperative complications. Therefore, curative lobectomies with LSND may be more suitable and practical for clinical stage IA solid-dominant patients with NSCLC.
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http://dx.doi.org/10.1016/j.cllc.2020.09.012DOI Listing
March 2021

Hydrogen sulfide, a signaling molecule in plant stress responses.

J Integr Plant Biol 2021 Jan;63(1):146-160

Laboratory Center of Life Sciences, College of Life Sciences, Nanjing Agricultural University, Nanjing, 210095, China.

Gaseous molecules, such as hydrogen sulfide (H S) and nitric oxide (NO), are crucial players in cellular and (patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H S is synthesized endogenously and serves as a signaling molecule throughout the plant life cycle. However, the mechanisms of H S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H S in plants. Additionally, we summarize the role of H S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H S regulates plant physiology.
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http://dx.doi.org/10.1111/jipb.13022DOI Listing
January 2021

Palmitic acid-modified bovine serum albumin nanoparticles target scavenger receptor-A on activated macrophages to treat rheumatoid arthritis.

Biomaterials 2020 11 4;258:120296. Epub 2020 Aug 4.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

Palmitic acid-modified bovine serum albumin (PAB) was synthetized and found to own remarkable scavenger receptor-A (SR-A) targeting ability in vitro and in vivo, through which activated macrophages took up PAB nanoparticles (PAB NPs) 9.10 times more than bovine serum albumin nanoparticles (BSA NPs) and PAB NPs could delivery anti-inflammatory drugs celastrol (CLT) to inflamed tissues more effectively than BSA NPs. Compared with chondroitin sulfate modified BSA NPs targeting activated macrophages via CD44, PAB NPs show a more prominent targeting effect whether in vivo or in vitro. And PAB also demonstrated excellent biosafety compared to maleylated BSA, a known SR-A ligand that was lethal in our study. Furthermore, in adjuvant-induced arthritis rats, CLT-PAB NPs significantly improved disease pathology at a lower CLT dose with high safety, compared with CLT-BSA NPs. In addition, compared with the existing ligands with SR-A targeting due to strong electronegativity, the enhanced electronegativity and introduced PA are both important for the SR-A targeting effect of PAB. Therefore, PAB provides a novel direction for the treatment of rheumatoid arthritis and design of new ligands of SR-A.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120296DOI Listing
November 2020
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