453 research outputs found
Protective effects on myocardial infarction model: delivery of schisandrin B using matrix metalloproteinase-sensitive peptide-modified, PEGylated lipid nanoparticles
No full textMingfeng Shao,1 Wenfang Yang,2 Guangying Han1 1Department of Cardiology, Linyi People’s Hospital, Linyi, Shandong, People’s Republic of China; 2Department of Internal Medicine, Linyi Hot Spring Hospital of Shandong Coal Mine, Linyi, Shandong, People’s Republic of China Purpose: Schisandrin B (Sch B) is clinically applied for the treatment of hepatitis and ischemic disease. However, its clinical efficacy is limited due to the poor solubility and low bioavailability. This study aimed to develop matrix metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)-modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch B SLNs), and to evaluate the therapeutic effect in the myocardial infarction model.Methods: PEG lipid and MMP-targeting peptide conjugate were synthesized. MMP-Sch B SLNs were prepared by solvent displacement technique. The physicochemical properties and pharmacokinetics of SLNs were investigated. In vivo effects on infarct size was evaluated in rats.Results: The successful synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior. Higher heart drug concentration and longer blood circulation times were achieved by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B SLNs by reducing the infarction size to the greatest extent.Conclusion: The modified SLNs may be a good choice for delivery of Sch B for the treatment of myocardial infarction. Keywords: cardiovascular diseases, CVDs, schisandrin B, matrix metalloproteinase, lipid nanoparticle
sj-docx-1-cll-10.1177_09636897221102902 – Supplemental material for Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing
No full textSupplemental material, sj-docx-1-cll-10.1177_09636897221102902 for Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing by Andi Wang, Wenjun Li, Fei Zhao, Zhongzheng Zheng, Ting Yang, Sanbin Wang, Jinsong Yan, Jianpin Lan, Shengjin Fan, Mingfeng Zhao, Jianpin Shen, Xin Li, Tonghua Yang, Quanyi Lu, Ying Lu, Hai Bai, Haiyan Zhang, Dali Cai, Ling Wang, Zhiyang Yuan, Erlie Jiang, Fang Zhou and Xianmin Song in Cell Transplantation</p
Validation of the use of the ROSIER scale in prehospital assessment of stroke
No full textAim: To determine the utility of the Recognition of Stroke in the Emergency Room (ROSIER) scale as a stroke recognition tool among Chinese patients in the prehospital setting. Materials and Methods: Compared with the Cincinnati Prehospital Stroke Scale (CPSS), emergency physicians prospectively used the ROSIER as a stroke recognition tool on suspected patients in the prehospital setting. And, the final discharge diagnosis of stroke or transient ischemic attack made by neurologists, after assessment and review of clinical symptomatology and brain imaging findings, was used as the reference standard for diagnosis in the study. Then, the ROSIER and the CPSS like sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), related coefficient (r) and Kappa value were calculated. Results: In this study, 540 of 582 suspected stroke patients met the study criteria. The CPSS showed a diagnostic Se of 88.77% (95% confidence intervals [CI] 86.11-91.43%), Sp of 68.79% (95% CI 64.88-72.70%), PPV of 87.40% (95% CI 85.97-88.83%), NPV of 71.52% (95% CI 67.71-75.33%) and r of 0.503. Relatively, the ROSIER showed a diagnostic Se of 89.97% (95% CI 87.44-92.64%), Sp of 83.23% (95% CI 80.08-86.38%), PPV of 92.66% (95% CI 90.46-94.86%), NPV of 77.91% (95% CI 74.41-81.41%) and r of 0.584. According to the final discharge diagnosis, both the ROSIER and the CPSS were associated with the final discharge diagnosis (P 0.05). Conclusions: The ROSIER is a sensitive and specific stroke recognition tool for health providers′ use among Chinese patients in the prehospital setting. However, it cannot be used to confidently rule out or identify stroke as a diagnosis. Comprehensive clinical assessment and further examination on potential stroke patients are still important and cannot be replaced. When it is difficult to objectively complete the ROSIER for patients, the CPSS could replace it in the prehospital setting
Development of red/near-infrared fluorescent molecules and macromolecules for biomedical applications
No full textRed/near infrared (R/NIR) fluorescence imaging based on organic materials has emerged as one of the most effective modalities in clinical practice due to the availability of biocompatible contrast agents, maneuverable instruments, and high spatial/temporal resolution with good sensitivity. To date, many organic fluorophores including organic small molecules and macromolecules have been developed as promising candidates for R/NIR bioimaging. However, the imaging efficacy of this technique has been limited by several challenges such as the lack of highly fluorescent R/NIR contrast agents, aggregation caused quenching (ACQ) effect, poor photostability, non-biodegradability and small Stokes shift. In this thesis, we have developed several strategies to overcome these challenges.
One of the strategies is to precisely control the molecular packing of the structures to improve the optical properties of R/NIR fluorophores. Specifically, Chapter 2 presents a new crystallization-induced-emission (CIE) fluorophore (denoted as Indigoid-B). A transition from amorphous to crystalline state of Indigoid-B was induced upon ultrasonication, accompanied with an enhancement of red emission at 600 nm. In Chapter 3, the aggregated states (H-, J-aggregates) of NIR dye pyrrolopyrrole cyanines (PPcys) in colloidal nanoparticles were investigated by modification of chemical structure, variation of concentration and the treatment of ultrasonication. Nanoparticles containing J-aggregates of PPcy exhibited a narrow emission band at 773 nm, a fluorescent quantum yield comparable to that of indocyanine green.
Another strategy of overcoming ACQ effect is developed in Chapter 4 and Chapter 5 by covalently conjugating biodegradable polycaprolactones (PCL) to red-emitting conjugated polymers (denoted as PFTB) and NIR dye PPcy. Two kinds of colloidal nanoparticles composed of PCL-grafted PFTB were prepared in the absence and presence of PCL-tethered PPcy, respectively. The presence of PCL-tethered PPcy enabled colloidal nanoparticles to emit at a longer wavelength through Förster resonance energy transfer (FRET). The introduction of PCL improved the quantum yields of both these two systems as compared to those without PCL, where FRET colloidal nanoparticles exhibited a NIR emission at 760 nm and a high quantum yield of 46%.
A strong candidate for clinical theranostics also calls for the improvement in optical properties of R/NIR imaging agents. In Chapter 6, we developed a kind of theranostic unimolecular micelles by grafting amphiphilic block copolymers from conjugated polymers PFTB. The surrounding amphiphilic scaffold helped to suppress aggregation of the central PFTB fluorophore, resulting in a high quantum yield of 22%. The hydrophobic layer of side chain was used to physically entrap drugs for chemotherapy. To address the potential problem of drug leakage, we utilized amphiphilic random copolymers containing drug-modified units as side chain of conjugated polymers instead in Chapter 7. The experiments of in vivo bioimaging and therapy demonstrated a good tumor-specific ability and long retention time in tumor.
Overall, this thesis has explored several ways to overcome the currently existing drawbacks of organic R/NIR fluorescent probes, especially aggregation caused quenching, non-degradability, small Stokes shifts, and further integrated the chemotherapy function with the R/NIR emitting unimolecular micelles for promising theranostic applications.Doctor of Philosophy (SCBE
Identification and Analysis of PANoptosis-Related Genes in Sepsis-Induced Lung Injury by Bioinformatics and Experimental Verification
No full textZhen Yang,1,* Xingyu Kao,1,* Na Huang,1 Kang Yuan,2 Jingli Chen,2 Mingfeng He2 1The Eighth School of Clinical Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong Province, People’s Republic of China; 2Foshan Hospital of Traditional Chinese Medicine, Foshan, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingli Chen; Mingfeng He, Email [email protected]; [email protected]: Sepsis-induced lung injury (SLI) is a serious complication of sepsis. PANoptosis, a novel form of inflammatory programmed cell death that is not yet to be fully investigated in SLI. Our research aims to screen and validate the signature genes of PANoptosis in SLI by bioinformatics and in vivo experiment.Methods: SLI-related datasets were downloaded from NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of SLI were identified and intersected with the PANoptosis gene set to obtain DEGs related to PANoptosis (SPAN_DEGs). Then, Protein–Protein Interaction (PPI) network and functional enrichment analysis were conducted based on SPAN_DEGs. SVM-REF, LASSO and RandomForest three algorithms were combined to identify the signature genes. The Nomogram and ROC curves were performed to predict diagnostic value. Immune infiltration analysis, correlation analysis and differential expression analysis were used to explore the immunological characterization, correlation and expression levels of the signature genes. Finally, H&E staining and qRT-PCR were conducted for further verification in vivo experiment.Results: Twenty-four SPAN_DEGs were identified by intersecting 675 DEGs with the 277 PANoptosis genes. Four signature genes (CD14, GSDMD, IL1β, and FAS) were identified by three machine learning algorithms, which were highly expressed in the SLI group, and had high diagnostic value in the diagnostic model. Moreover, immune infiltration analysis showed that most immune cells and immune-related functions were higher in the SLI group than those in the control group and were closely associated with the signature genes. Finally, it was confirmed that the cecum ligation and puncture (CLP) group mice showed significant pathological damage in lung tissues, and the mRNA expression levels of CD14, IL1β, and FAS were significantly higher than the sham group.Conclusion: CD14, FAS, and IL1β may be the signature genes in PANoptosis to drive the progression of SLI and involved in regulating immune processes.Keywords: sepsis, lung injury, PANoptosis, machine learning, immune infiltration analysi
Exploring the Anti-PANoptosis Mechanism of Dachaihu Decoction Against Sepsis-Induced Acute Lung Injury: Network Pharmacology, Bioinformatics, and Experimental Validation
No full textZhen Yang,1,2 Xingyu Kao,1,2 Lin Zhang,3 Na Huang,1,2 Jingli Chen,2 Mingfeng He2 1The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine, Foshan, Guangdong, People’s Republic of China; 2Foshan Hospital of Traditional Chinese Medicine, Foshan, Guangdong, People’s Republic of China; 3Department of Cardiovascular, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Mingfeng He, Foshan Hospital of Traditional Chinese Medicine, Foshan, Guangdong, People’s Republic of China, Email [email protected]: Dachaihu decoction (DCHD) is a common Chinese medicine formula against sepsis-induced acute lung injury (SALI). PANoptosis is a novel type of programmed cell death. Nevertheless, The mechanisms of DCHD against SALI via anti-PANoptosis remains unknown.Methods: First, we identified the intersecting targets among DCHD, SALI, and PANoptosis using relevant databases and published literature. Then, protein-protein interaction (PPI) network, molecular docking, and functional enrichment analysis were conducted. In vivo, cecal ligation and puncture (CLP) was used to construct a sepsis mouse model, and the therapeutic effects of DCHD on SALI were evaluated using hematoxylin and eosin (H&E) staining, quantitative real-time PCR (qRT-PCR), and ELISA. Finally, qRT-PCR, immunofluorescence staining, and Western blotting were used to verify the effect of DCHD-containing serum (DCHD-DS) on LPS-induced RAW 264.7 macrophages in vitro.Results: 82 intersecting targets were identified by mapping the targets of DCHD, SALI, and PANoptosis. Enrichment analysis showed that DCHD against SALI via anti-PANoptosis by modulating tumor necrosis factor (TNF), AGE-RAGE, phosphoinositide 3-kinase (PI3K)-AKT, and Toll-like receptor signaling pathways by targeting Casp3, cellular tumor antigen p53 (TP53), B-cell lymphoma 2 (Bcl2), toll-like receptor-4 (TLR4), STAT3, STAT1, RELA, NF-κB1, myeloid cell leukemia-1 (MCL1), JUN, IL-1β, HSP90AA1, Casp9, Casp8, and Bcl2l1. Molecular docking analysis revealed that the key components of DCHD have a high binding affinity to the core targets. In vivo, DCHD improved lung histopathological injury, reduced inflammatory factor expression, and alleviated oxidative stress injury in lung tissues. In vitro, DCHD-DS alleviated cell morphology changes, the release of pro-inflammatory factors, and p65 nucleus aggregation. Furthermore, we verified that DCHD-DS inhibited PANoptosis by downregulating the PI3K/AKT/NF-κB signalling pathway.Conclusion: DCHD attenuates SALI by inhibiting PANoptosis via control of the PI3K/AKT/NF-κB pathway. Our study provides a solid foundation for investigating the mechanisms of DCHD and its clinical application in the treatment of SALI. Keywords: Dachaihu decoction, sepsis-induced acute lung injury, PANoptosis, network pharmacology, bioinformatic
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Dynamics of Advice Network and Knowledge Contribution: A Longitudinal Social Network Analysis
No full textOnline communities have become an increasingly popular channel for social interaction, enabling knowledge and opinion sharing across a board range of topics and contexts. Their viability and sustainability depends largely on contributions from community members in terms of time, resources, and knowledge. However, how individuals' knowledge contribution behavior changes over time and what network structural characteristics influence individuals' contribution behavior is not well understood. This study investigates "co-evolution" of social networks (i.e. advice network) and knowledge contribution behavior thorough a lens of social selection and social influence mechanism. This study are particularly interested in examining the dynamics of the advice network ties and the knowledge contribution behavior in the context of virtual financial communities in which people voluntarily participate to exchanges investing-related information. Unlike popular friendship-based online social networks, virtual financial communities in this study enables members to construct their own advice network by adding, maintaining, or terminating advice ties. Changes in network ties are referred to as social selection, while changes in individuals' behavior in response to the current network position are referred to as social influence. Dynamic network modeling is applied to investigate effects of social selection and influence separately and then examine the interplay between social selection and behavioral influence. Examination of such effects both separately and simultaneously requires a longitudinal data that capture dynamic changes in both the advice ties and the behavior under study.Release after 09-Aug-2014Originally embargoed until 09-Aug-2014; further restricted on 22-Jan-2016 per author request / K
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