147 research outputs found

    Nanoparticle-Delivered microRNA-153-3p Alleviates Myocardial Infarction-Induced Myocardial Injury in a Rat Model

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    Although microRNA-153-3p (miR-153-3p) has been demonstrated to confer protective roles in ischemia/reperfusion injury, its potential role in myocardial infarction (MI) remains undefined. Small-molecule modifiers and nanoparticles loaded with microRNAs (miRNAs) have emerged as potential therapeutic reagents for MI treatment. In this study, we prepared liposome nanoparticles, hyaluronic acid (HA)-cationic liposomes (CLPs) complex, for the delivery of miR-153-3p and delineated the mechanistic actions of miR-153-3p modified by nHA-CLPs in MI-induced injury. Our data suggested that nHA-CLPs-loaded miR-153-3p protected cardiomyocytes against MI-induced cardiomyocyte apoptosis and myocardial injury. miR-153-3p was bioinformatically predicted and experimentally verified to bind to Krüppel-like factor 5 (KLF5) 3’UTR and negatively regulate its expression. Hypoxia was adopted to stimulate MI-induced injury to cardiomyocytes in vitro, in which miR-153-3p presented anti-apoptotic potential. However, restoration of KLF5 reversed this anti-apoptotic effect of miR-153-3p. Furthermore, KLF5 was demonstrated to be an activator of the NF-κB pathway. KLF5 enhanced cardiomyocyte apoptosis and inflammation under hypoxic conditions through NF-κB pathway activation, while nHA-CLPs-loaded miR-153-3p suppressed inflammation by blocking the NF-κB pathway. Collectively, our findings suggested the cardioprotective role of miR-153-3p against MI and the successful delivery of miR-153-3p by nHA-CLPs. The identification of KLF5-mediated activation of NF-κB pathway as an apoptotic and inflammatory mechanism aids in better understanding of the biology of MI and development of novel therapeutic strategies for MI

    Aggregation-Induced Enhancement Effect of Gold Nanoparticles on Triplet Excited State

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    Remarkable optical properties are posed with gold nanoparticles (AuNPs) due to the excitation of localized surface plasmon resonances, which makes AuNPs affect strongly both the ground state and the excited state of adjacent organic molecules. Compared with the ground state, the effect of AuNPs on excited state of organic molecules is not always fully understood. Here, we performed transient UV–vis absorption experiments to monitor the triplet excited state formation of three cationic dyes and one anionic dye in the presence of two types of gold nanoparticles: the citrate-stabilized AuNPs and ATP-protected AuNPs. It is found that the three cationic dyes can cause efficient aggregation of citrate-stabilized AuNPs, leading to AuNPs aggregates with varied size, whereas the ATP-protected AuNPs can be sustained in the monodispersed state. By comparing the circumstances of aggregated AuNPs and monodispersed AuNPs, we demonstrate that the enhancement effect on triplet excited state formation results from the aggregation of gold nanoparticles and depends on the aggregation size. These findings reveal the aggregation induced plasmon field interaction of AuNPs with excited state population dynamics and may enable new applications of aggregated metal nanoparticles, where aggregates can serve as stronger plasmonic nanoantennas

    The XVP/ NAC003 protein associates with the plasma membrane through KR rich regions and translocates to the nucleus by changing phosphorylation status

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    Membrane localized transcription factors play essential roles in various plant developmental processes. The XVP/NAC003 protein is a NAC domain transcription factor associated with the plasma membrane and involved in the TDIF-PXY signaling during vascular development. We report here the mechanisms of XVP membrane localization and its nuclear translocation. Using a transient transformation approach, we found that XVP is associated with the plasma membrane through positively charged KR-rich regions. Mutagenesis studies found that the threonine amino acid at position 354 (T354) is critical for XVP translocation to the nucleus. In particular, the threonine to alanine mutation (T354A) resulted in a partial nucleus localization, while threonine to aspartic acid (T354D) mutation showed no effect on protein localization, indicating that dephosphorylation at T354 may serve as a nucleus translocation signal. This research sheds new light on the nucleus partitioning of plasma membrane-associated transcription factors.</p

    Energy Storage System Based on Recycled Polypropylene and Its Use in Lithium–Sulfur and Lithium-Ion Batteries

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    Nontoxic, eco-friendly, and high-energy-density sulfurated poly(propylene) (S/PP-waste) has been prepared in a one-step vulcanization process from recycled poly(propylene) waste and used as a cathode material in lithium–sulfur (Li–S) batteries. A sulfur loading of up to 50.4 wt % was achieved. In S/PP-waste, the sulfur is covalently bound to the polymer matrix, selectively resulting in a solid phase transition during charge and discharge. Consequently, the polysulfide shuttle can be avoided, which results in satisfactory electrochemical performance with ultralong cycle life and a low capacity decay per cycle of ∼0.018% at 0.5C. S/PP-waste was also explored for the first time as an anode material in LiMn2O4-based Li-ion full cells. Its good electrochemical performance as well as its recycled nature make it a promising energy storage material for the future

    Oxygen Self-Production Red Blood Cell Carrier System for MRI Mediated Cancer Therapy: Ferryl-Hb, Sonodynamic, and Chemical Therapy

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    Hypoxia in tumors can lead to insufficient oxygen supply during sonodynamic therapy (SDT), which in turn strengthens tumor resistance to sonodynamic efficacy. To conquer hypoxia in tumors and improve the treatment effectiveness, we developed oxygen self-production red blood cell (RBC) carrier system to decompose tumor endogenic H2O2 into O2 and combine triplex cancer therapy: ferryl-hemoglobin (ferryl-Hb), sonodynamic, and chemical therapy. Both hydrophilic sonosensitizer and doxorubicin (DOX) were encapsulated inside RBCs (DOX/Mn-TPPS@RBCs). The drug release can be improved by combining the effects of H2O2 and ultrasonic irradiation. Here, we introduced a contrast agent, meso-tetra (4-sulfonatephenyl) porphyrinate manganese­(III) complex (Mn-TPPS), which could be used to enhance the signal intensity of magnetic resonance imaging (MRI) of the tumor site. The feasibility of Mn-TPPS as a sonosensitizer was investigated during SDT. Importantly, DOX/Mn-TPPS@RBCs overcame hypoxia in the tumor and improved the efficacy of SDT owing to the O2 generation by the catalase-catalyzed decomposition of tumor endogenic H2O2. Hemoglobin was simultaneously oxidized into highly oxidative ferryl-Hb species by H2O2 and reactive oxygen species, resulting in cytotoxicity. Overall, this drug delivery system is a promising therapeutic agent involving in situ production of oxygen inside the tumor, triplex therapy, and MRI

    Identification of OLA1 as a Novel Protein Target of Vitexin to Ameliorate Dextran Sulfate Sodium-Induced Colitis with Tissue Thermal Proteome Profiling

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    Vitexin, which exists in various medicinal plants and food sources, has recently received increasing attention because of its anti-inflammatory properties. This study aims to identify the protein target of vitexin that ameliorates dextran sulfate sodium (DSS)-induced colitis. The results showed that vitexin not only alleviated the clinical symptoms and colonic damage in mice with DSS-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, ICAM, and VCAM) and enhanced the expression of barrier-associated proteins (ZO-1, Occludin, and E-cadherin). Based on tissue thermal proteome profiling (Tissue-TPP) and molecular docking, OLA1 was creatively identified as a potential protein target for vitexin. Further siRNA-mediated knockdown of the OLA1 gene in Caco-2 cells demonstrated the ability of OLA1 to increase Nrf2 protein expression and, thus, mediated the anti-inflammatory effects of vitexin. Interaction of the OLA1–vitexin complex with Keap1 protein to disrupt the Keap1-Nrf2 interaction may be required for activating Nrf2. Our findings revealed a novel role for OLA1 as a protein target of vitexin that contributes to its anti-inflammatory action by activating Nrf2, which may provide a promising molecular mechanism for novel therapeutic strategies to treat colitis and the associated systemic inflammation

    Table1_PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study.DOCX

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    Background & Aims: Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer treatment, and ICI-related toxicities (i.e., immune-related adverse events (irAEs) have been reported in many clinical studies. However, the toxicity data of real-world have not been fully assessed.Methods: Patients with histologically confirmed solid tumors who had been treated with PD-1 inhibitors were included in the study. Patient data were collected from electronic medical records, including basic characteristics, data of irAEs, management and outcome. Incidences of irAEs were pooled and compared, and the risk of irAEs was also analyzed.Results: A total of 362 solid tumor patients treated with sintilimab (n = 171), camrelizumab (n = 60), toripalimab (n = 72), and pembrolizumab (n = 59) were included. In total, any grade irAEs, grade 1–2 irAEs, and grade ≥3 irAEs accounted for 47.24%, 38.67% and 8.56% of cases, reapectively. Further, 29.24% of patients discontinued immunotherapy due to irAEs, with pneumonitis being the main reason for discontinuation. By comparing the toxicity profiles between different ICIs, we found that reactive capillary haemangiomas were camrelizumab-specific. Additionally, the frequency of irAEs was association with ICIs type, the pooled incidence (standardized rate) of irAEs related to sintilimab, camrelizumab, toripalimab and pembrolizumab were 55.56% (52.81%), 48.33% (55.55%), 33.33% (29.23%) and 38.98% (38.29%), respectively. Sintilimab and camrelizumab had higher incidences of any grade and grade 1–2 than toripalimab (55.56% vs. 33.33%, p = 0.002; 48.54% vs. 25.00%, p = 0.0001) and pembrolizumab (55.56% vs. 38.98%, p = 0.0028; 48.54% vs. 25.42%, p = 0.002), while the grade ≥3 irAEs of pembrolizumab (13.56%) were approximately 1.63- to 1.93-fold higher than other ICIs, and the standardized grade ≥3 of pembrolizumab was significantly higher than that of sintilimab (13.21% vs. 7.12%, p = 0.026), especially for grade ≥3 pneumonitis. Multivariate analysis found that cumulative cycles of ICI (OR = 1.081; 95% CI: 1.023–1.142; p = 0.006), and lung cancer (OR = 1.765; 95% CI: 1.105–2.820; p = 0.017) were independent risk factors for irAEs.Conclusion: The frequency of irAEs is associated with ICI type. The pooled incidence of irAEs related to sintilimab and pneumonitis caused by pembrolizumab were higher. These data indicate the importance of having different monitoring priorities for different PD-1 inhibitors.</p

    Comparison of different hybridization probes functionalized magnetic microparticles.

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    <p>(<b>A</b>) Functionalized magnetic microparticles MMP-p1, -p2, -p3, -p4, -p5, -p6, -p7, -p8 and -p9 were incubated with the DNA derived from different PCV2 representative strains in hybridization buffer at 40°C for 30 min, followed by washing and magnetic separation. MMP-DNA complex were detected by PCV2-specific PCR and PCV1-specific PCR. M: Trans 2000 Plus DNA Marker; 1: AF381176; 2: DQ104423; 3: AF112862; 4: EU366323; 5: AY579893; 6: AY391729; 7: FJ644927; 8: AY291317; 9: AY484410; 10: AY181947; 11: KC800634; 12: KC800636; 13: KC800639; 14: KC800644; 15: KC800646; 16: AY193712 (PCV1). (B) Identification of different hybridization probes functionalized MMPs. The indicated two PCV2 representative strains were incubated with MMP-p1, -p2, -p3, -p4, -p5, -p6, -p7, -p8 and -p9, respectively, followed by PCV2 specific PCR detection. M: Trans 2000 Plus DNA Marker; 1: MMP1; 2: MMP2; 3: MMP3; 4: MMP4; 5: MMP5; 6: MMP6; 7: MMP7; 8: MMP8; 9: MMP9.</p
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