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1.
Biomaterials ; 312: 122722, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39096841

ABSTRACT

Ferroptosis, a recently identified form of cell death, holds promise for cancer therapy, but concerns persist regarding its uncontrolled actions and potential side effects. Here, we present a semiconducting polymer nanoprodrug (SPNpro) featuring an innovative ferroptosis prodrug (DHU-CBA7) to induce sono-activatable ferroptosis for tumor-specific therapy. DHU-CBA7 prodrug incorporate methylene blue, ferrocene and urea bond, which can selectively and specifically respond to singlet oxygen (1O2) to turn on ferroptosis action via rapidly cleaving the urea bonds. DHU-CBA7 prodrug and a semiconducting polymer are self-assembled with an amphiphilic polymer to construct SPNpro. Ultrasound irradiation of SPNpro leads to the production of 1O2 via sonodynamic therapy (SDT) of the semiconducting polymer, and the generated 1O2 activated DHU-CBA7 prodrug to achieve sono-activatable ferroptosis. Consequently, SPNpro combine SDT with the controlled ferroptosis to effectively cure 4T1 tumors covered by 2-cm tissue with a tumor inhibition efficacy as high as 100 %, and also completely restrain tumor metastases. This study introduces a novel sono-activatable prodrug strategy for regulating ferroptosis, allowing for precise cancer therapy.


Subject(s)
Ferroptosis , Mice, Inbred BALB C , Polymers , Prodrugs , Semiconductors , Ferroptosis/drug effects , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/therapeutic use , Animals , Polymers/chemistry , Female , Cell Line, Tumor , Mice , Ultrasonic Therapy/methods , Nanoparticles/chemistry , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Singlet Oxygen/metabolism
2.
ChemMedChem ; : e202400410, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264862

ABSTRACT

Nanoparticles can enhance drugs accumulating at the tumor site and hold tremendous promise for achieving effective tumor treatment. However, due to the complexity of cancer heterogeneity and suppressive tumor microenvironment, the delivery of traditional nanoparticles has poor infiltration and off-target effects, making it difficult to control the drug release rate and causing off-target toxicity. In recent years, cell membrane-coated biomimetic nanoparticles have been developed, which have both the natural characteristics of biomembranes and the physical characteristics of traditional nanoparticles, thus improving the homologous targeting ability of nanoparticles to tumor cells and better biocompatibility. In this paper, we reviewed the application of single cell membrane and hybrid cell membrane-coated biomimetic nanoparticles in the integration for tumor diagnosis and treatment. We talked about the preparation methods of cell membrane-coated nanoparticles, the targeting mechanisms, and the effects of imaging and therapeutic outcomes of different cell membrane-coated biomimetic nanoparticles in detail. Finally, we discussed the existing problems and prospects of cell membrane-coated biomimetic nanomaterials.

3.
J Mater Chem B ; 12(35): 8616-8625, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39140256

ABSTRACT

Similar to clinically applied thermal ablation techniques, the cellular necrosis that occurs during photothermal tumor therapy (PTT) can induce inflammatory response, severely compromising the therapeutic efficacy and clinical translation of the PTT. Inspired by the remarkable ROS-scavenging activity and high photothermal efficiency of molybdenum-based polyoxometalate (POM) and the immunostimulatory effect of cyclic dinucleotides (CDNs), a NIR-responsive and injectable DNA-mediated hybrid hydrogel (CDN-POM) has been developed. The hydrogels have superior photothermal efficiency (43.41%) to POM, impressive anti-inflammatory capability and prolonged intratumoral CDN-releasing behavior, thus enabling synergistic anti-tumor therapeutic outcomes. Meanwhile, local treatment induced by CDN-POM hydrogels displays minimal side effects on normal tissue. Taking advantage of the high phototherapeutic effect, ROS-scavenging activity and sustained CDN release of CDN-POM hydrogels, a novel combined approach that integrates photothermal therapy and immunotherapy of breast tumor is successfully pioneered.


Subject(s)
Hydrogels , Immunotherapy , Infrared Rays , Hydrogels/chemistry , Immunotherapy/methods , Animals , Mice , Humans , Molybdenum/chemistry , Molybdenum/pharmacology , Female , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Mice, Inbred BALB C , Photothermal Therapy , Phototherapy/methods , Cell Proliferation/drug effects , Particle Size , Injections , Breast Neoplasms/therapy , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology
4.
Adv Sci (Weinh) ; : e2406750, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39159216

ABSTRACT

Glioblastoma (GBM) is one of the deadliest primary brain tumors, but its diagnosis and curative therapy still remain a big challenge. Herein, neutrophil-targeting semiconducting polymer nanotheranostics (SSPNiNO) is reported for second near-infrared (NIR-II) fluorescence imaging-guided trimodal therapy of orthotopic glioblastoma in mouse models. The SSPNiNO are formed based on two semiconducting polymers acting as NIR-II fluorescence probe as well as photothermal conversion agent, respectively. A thermal-responsive nitric oxide (NO) donor and an adenosine 2A receptor (A2AR) inhibitor are co-integrated into SSPNiNO to enable trimodal therapeutic actions. SSPNiNO are surface attached with a neutrophil-targeting ligand to mediate their effective delivery into orthotopic GBM sites via a "Trojan Horse" manner, enabling high-sensitive NIR-II fluorescence imaging. Upon NIR-II light illumination, SSPNiNO effectively generates heat via NIR-II photothermal effect, which not only kills tumor cells and induces immunogenic cell death (ICD), but also triggers controlled NO release to strengthen tumor ICD. Additionally, the encapsulated A2AR inhibitor can modulate immunosuppressive tumor microenvironment by blocking adenosine-A2AR pathway, which further boosts the antitumor immunological effect to observably suppress the orthotopic GBM progression. This study can provide a multifunctional theranostic nanoplatform with cumulative therapeutic actions for NIR-II fluorescence imaging-guided effective GBM treatment.

5.
Langmuir ; 40(32): 17141-17150, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39096500

ABSTRACT

In this work, a nonequilibrium molecular dynamics simulation is utilized to explore the effect of network structure of graphene (GE) on the thermal conductivity of the GE/polydimethylsiloxane (PDMS) composite. First, the thermal conductivity of composites rises with increasing volume fraction of GE. The heat transfer ability via the GE channel is found to be nearly the same by analyzing the GE-GE interfacial thermal resistance (ITR). More heat energy is transferred via the GE channel at the high volume fraction of GE by calculating the GE heat transfer ratio, which leads to the high thermal conductivity. Then, the thermal conductivity of composites rises with increasing stacking area between GE, which is attributed to both the strong heat transfer ability via the GE channel and the high GE heat transfer ratio. Following it, the thermal conductivity of composites first rises and then drops down with increasing defect density for a single vacancy defect while it continuously increases for a single void defect. The heat transfer ability between GE is enhanced due to the formation of interlayer covalent bonds. However, the intrinsic thermal conductivity of GE is significantly reduced for a single vacancy defect while it remains relatively well for a single void defect. As a result, the GE heat transfer ratio is maximum at the intermediate defect density for a single vacancy defect while it rises monotonically for a single void defect, which can rationalize the thermal conductivity. Meanwhile, the relationship between ITR and the number of covalent bonds can be described by an empirical equation. Finally, the thermal conductivity for the stacked structure is larger than that for the noncontact structure or the intersected structure. In summary, this work provides a clear and novel understanding of how the network structure of GE influences the thermal conductivity of the GE/PDMS composite.

6.
ACS Appl Mater Interfaces ; 16(36): 48329-48341, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39189954

ABSTRACT

Intelligent wearable textiles have garnered attention and advancement, particularly in the realms of thermotherapy and health monitoring. As a critical component of intelligent wearable textiles, conductive fibers are expected to have long-term stable and durable conductivity. In this work, a highly stretchable and conductive fiber based on tannic acid/polypyrrole was developed. The conductive network was formed by doping TA into PPy, resulting in enhanced stretchability of PPy on the surface of PU. TA also improves the interface interaction between PPy and PU to gain more firm attachment of PPy, which achieves high conductivity (0.89 ± 0.23 S/cm) and durability. Furthermore, the stretchable conductive fiber also exhibited intelligent responses to electricity, light, and deformation. They can serve as heat sources under the action of electricity and light (temperature was raised to 42 °C under 4 V and 54 °C under solar radiation stimuli) and can also monitor the movements of humans, making them potential applications in thermotherapy textiles and intelligent sensing equipment. A PU/TA/PPy-based all-in-one smart wearable system was fabricated using textile molding technology capable of all-weather thermal therapy and motion detection. This fiber fabrication technology and integrated system offer insights for the future development of smart wearable devices.


Subject(s)
Electric Conductivity , Polymers , Pyrroles , Tannins , Textiles , Wearable Electronic Devices , Tannins/chemistry , Pyrroles/chemistry , Polymers/chemistry , Humans , Hyperthermia, Induced , Polyphenols
7.
Chem Commun (Camb) ; 60(71): 9630, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39162126

ABSTRACT

Correction for 'Radiopharmaceutical-activated silicon naphthalocyanine nanoparticles towards tumor photodynamic therapy' by Tingting Wang et al., Chem. Commun., 2024, https://doi.org/10.1039/d4cc03281k.

8.
Exploration (Beijing) ; 4(4): 20230100, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39175882

ABSTRACT

Sonodynamic therapy (SDT) has been explored for cancer therapy, especially for deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited due to the complicated tumor microenvironment. This study reports the construction of oxygen-carrying semiconducting polymer nanoprodrugs (OSPNpro) for deep tumor treatment via combining amplified SDT with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic semiconducting polymer as the sonosensitizer, and reactive oxygen species (ROS)-responsive prodrug are co-loaded into a nanoparticle system, leading to the formation of these polymer nanoprodrugs. Such OSPNpro show an effective accumulation in tumor tissues after systemic administration, in which they deliver oxygen to relieve tumor hypoxia microenvironment and thus mediate amplified SDT via producing ROS under ultrasound (US) irradiation, even when the tumors are covered with a 2-cm chicken breast tissue. In addition, the ROS-responsive prodrugs are activated by the generated ROS to trigger pyroptosis of tumor cells. Such a sono-pyroptosis induces a strong antitumor immunity with obviously higher level infiltrations of effector immune cells into tumors. Therefore, OSPNpro-based combinational therapy can greatly inhibit the growth of 2-cm chicken breast tissue-covered deep tumors and suppress tumor metastasis. This study offers a prodrug nanoplatform for treatment of deep tumor via sono-pyroptosis strategy.

9.
Chem Commun (Camb) ; 60(68): 9082-9084, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39105653

ABSTRACT

Naphthalocyanine-based agents exhibit huge potential in photodynamic therapy, yet their photodynamic performance is restricted by the penetration depth of the external laser. Herein, we employed 18F-FDG as an internal light source to excite silicon naphthalocyanine nanoparticles to simultaneously circumvent radiative transition and boost 1O2 generation for tumor suppression.


Subject(s)
Nanoparticles , Photochemotherapy , Photosensitizing Agents , Nanoparticles/chemistry , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Animals , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacology , Mice , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/diagnostic imaging , Singlet Oxygen/metabolism , Singlet Oxygen/chemistry , Silicon/chemistry
10.
Mol Cell Neurosci ; 130: 103957, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39111720

ABSTRACT

BACKGROUND: Microglia is the primary source of inflammatory factors during migraine attacks. This study aims to investigate the role of microglia related genes (MRGs) in migraine attacks. METHODS: The RNA sequencing results of migraineurs and the panglaodb database were used to obtain differentially expressed genes (DEGs) in migraine related to microglia. A migraine rat model was established for validating and localizing of the MRGs, and subsequent screening for target genes was conducted. A shRNA was designed to interference the expression of target genes and administered into the trigeminal ganglion (TG) of rats. Pain sensitivity in rats was evaluated via the hot water tail-flick (HWTF) and formalin-induced pain (FIP) experiments. ELISA was used to quantify the levels of inflammatory cytokines and CGRP. WB and immunofluorescence assays were applied to detect the activation of microglia. RESULTS: A total of five DEGs in migraine related to microglia were obtained from RNA sequencing and panglaodb database. Animal experiments showed that these genes expression were heightened in the TG and medulla oblongata (MO) of migraine rats. The gene S100A8 co-localized with microglia in both TG and MO. The HWTF and FIP experiments demonstrated that interference with S100A8 alleviated the sense of pain in migraine rats. Moreover, the levels of TNFα, IL-1ß, IL-6, and CGRP in the TG and MO of rats in the model rats were increased, and the expression of microglia markers IBA-1, M1 polarization markers CD86 and iNOS was upregulated. Significantly, interference with S100A8 reversed these indicators. CONCLUSION: Interference with S100A8 in microglia increased the pain threshold during migraine attacks, and inhibited neuroinflammation and microglia activation.


Subject(s)
Calgranulin A , Microglia , Migraine Disorders , Neuroinflammatory Diseases , Rats, Sprague-Dawley , Animals , Microglia/metabolism , Migraine Disorders/metabolism , Migraine Disorders/genetics , Rats , Male , Calgranulin A/metabolism , Calgranulin A/genetics , Neuroinflammatory Diseases/metabolism , Trigeminal Ganglion/metabolism , Disease Models, Animal
11.
Biomater Adv ; 163: 213962, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39032435

ABSTRACT

Solid tumors create a hypoxic microenvironment and this character can be utilized for cancer therapy, but the hypoxia levels are insufficient to achieve satisfactory therapeutic benefits. Some tactics have been used to improve hypoxia, which however will cause side effects due to the uncontrolled drug release. We herein report near-infrared (NIR) photoactivatable three-in-one nanoagents (PCT) to aggravate tumor hypoxia and enable amplified photo-combinational chemotherapy. PCT are formed based on a thermal-responsive liposome nanoparticle containing three therapeutic agents: a hypoxia responsive prodrug tirapazamine (TPZ) for chemotherapy, a vascular targeting agent combretastatin A-4 (CA4) for vascular disturbance and a semiconducting polymer for both photodynamic therapy (PDT) and photothermal therapy (PTT). With NIR laser irradiation, PCT generate heat for PTT and destructing thermal-responsive liposomes to achieve activatable releases of TPZ and CA4. Moreover, PCT produce singlet oxygen (1O2) for PDT via consuming tumor oxygen. CA4 can disturb the blood vessels in tumor microenvironment to aggravate the hypoxic microenvironment, which results in the activation of TPZ for amplified chemotherapy. PCT thus enable PTT, PDT and hypoxia-amplified chemotherapy to afford a high therapeutic efficacy to almost absolutely eradicate subcutaneous 4 T1 tumors and effectively inhibit tumor metastases in lung and liver. This work presents an activatable three-in-one therapeutic nanoplatform with remotely controllable and efficient therapeutic actions to treat cancer.


Subject(s)
Infrared Rays , Liposomes , Nanoparticles , Photochemotherapy , Tirapazamine , Animals , Humans , Photochemotherapy/methods , Tirapazamine/pharmacology , Tirapazamine/chemistry , Tirapazamine/therapeutic use , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Mice , Tumor Microenvironment/drug effects , Cell Line, Tumor , Photothermal Therapy/methods , Stilbenes/pharmacology , Stilbenes/therapeutic use , Stilbenes/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/therapeutic use , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Tumor Hypoxia/drug effects
12.
Medicine (Baltimore) ; 103(29): e38896, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39029045

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the role of legumain in metabolic dysfunction, diagnosis, and prognosis in patients with atherosclerosis. METHODS: Plasma levels of legumain from patients with atherosclerosis (n = 320) and healthy controls (n = 320), expression of legumain in atheromatous plaque and secreted from monocyte-derived macrophages were measured using enzyme-linked-immunosorbent assay, reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and fluorescence. RESULTS: Data demonstrated that atherosclerotic patients had higher plasma level of legumain than healthy controls, which was a diagnostic and prognostic marker and corrected with the degree of atherosclerosis. It found that atheromatous plaque and endothelial cell had higher legumain expression than non-atherosclerotic arteries (controls). Legumain showed significantly increased secretion from pro-inflammatory M1 compared to pro-resolving M2 macrophages during monocyte-derived macrophages, which was localized to structures resembling foam cells. CONCLUSION: In conclusion, our data indicate that legumain expression is upregulated in both plasma and plaques of patients with atherosclerosis, which is associated with metabolic dysfunction of endothelial cell and might be a diagnostic and prognostic marker of atherosclerosis.


Subject(s)
Atherosclerosis , Biomarkers , Cysteine Endopeptidases , Macrophages , Humans , Cysteine Endopeptidases/metabolism , Cysteine Endopeptidases/blood , Male , Female , Atherosclerosis/diagnosis , Atherosclerosis/metabolism , Prognosis , Middle Aged , Macrophages/metabolism , Biomarkers/blood , Biomarkers/metabolism , Plaque, Atherosclerotic/metabolism , Aged , Case-Control Studies , Up-Regulation , Adult
13.
J Nanobiotechnology ; 22(1): 313, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840120

ABSTRACT

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.


Subject(s)
Breast Neoplasms , CD56 Antigen , Killer Cells, Natural , Photochemotherapy , Polyethylene Glycols , Breast Neoplasms/therapy , Humans , Female , Animals , Photochemotherapy/methods , Mice , Polyethylene Glycols/chemistry , Cell Line, Tumor , CD56 Antigen/metabolism , Immunotherapy, Adoptive/methods , Apoptosis/drug effects , Magnetic Resonance Imaging/methods , Mice, Inbred BALB C , Mice, Nude
14.
J Mater Chem B ; 12(25): 6091-6101, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38828732

ABSTRACT

Due to the rapid progression and aggressive metastasis of breast cancer, its diagnosis and treatment remain a great challenge. The simultaneous inhibition of tumor growth and metastasis is necessary for breast cancer to obtain ideal therapeutic outcomes. We herein report the development of radioactive hybrid semiconducting polymer nanoparticles (SPNH) for imaging-guided tri-modal therapy of breast cancer. Two semiconducting polymers are used to form SPNH with a diameter of around 60 nm via nano-coprecipitation and they are also labeled with iodine-131 (131I) to enhance the imaging functions. The formed SPNH show good radiolabeling stability and excellent photodynamic and photothermal effects under 808 nm laser irradiation to produce singlet oxygen (1O2) and heat. Moreover, SPNH can generate 1O2 with ultrasound irradiation via their sonodynamic properties. After intravenous tail vein injection, SPNH can effectively accumulate in the subcutaneous 4T1 tumors of living mice as verified via fluorescence and single photon emission computed tomography (SPECT) imaging. With the irradiation of tumors using an 808 nm laser and US, SPNH mediate photodynamic therapy (PDT), photothermal therapy (PTT) and sonodynamic therapy (SDT) to kill tumor cells. Such a tri-modal therapy leads to an improved efficacy in inhibiting tumor growth and suppressing tumor metastasis compared to the sole SDT and combinational PDT-PTT. This study thus demonstrates the applications of SPNH to diagnose tumors and combine different therapies for effective breast cancer treatment.


Subject(s)
Breast Neoplasms , Iodine Radioisotopes , Nanoparticles , Photochemotherapy , Polymers , Semiconductors , Animals , Nanoparticles/chemistry , Mice , Female , Polymers/chemistry , Iodine Radioisotopes/chemistry , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/therapy , Mice, Inbred BALB C , Humans , Cell Proliferation/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Particle Size , Tomography, Emission-Computed, Single-Photon , Photothermal Therapy , Mammary Neoplasms, Experimental/diagnostic imaging , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathology
15.
Int J Cardiovasc Imaging ; 40(7): 1401-1411, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38842665

ABSTRACT

The precise features of lesions in non-ST-segment elevation myocardial infarction (NSTEMI) patients with total occlusion (TO) of the infarct-related artery (IRA) are still unclear. This study employs optical coherence tomography (OCT) to investigate pathological features in NSTEMI patients with or without IRA TO and explores the relationship between thrombus types and IRA occlusive status. This was a single-center retrospective study. A total of 202 patients diagnosed with NSTEMI were divided into two groups: those with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 before percutaneous coronary intervention (PCI) (referred to as the TO group, n = 100) and those TIMI flow grade 1-3 (referred to as the Non-TO group, n = 102). Baseline characteristics, coronary angiography findings, and OCT results were collected. Multivariate logistic analysis identified factors influencing TO in NSTEMI. The category of NSTEMI was further subdivided based on the type of electrocardiogram (ECG) into two subgroups: ST segment unoffset myocardial infarction (STUMI) and ST segment depression myocardial infarction (STDMI). This division allows for a more specific classification of NSTEMI cases. The TO group had a younger age, higher male representation, more smokers, lower hypertension and cerebrovascular disease incidence, lower left ventricular ejection fraction (LVEF), and higher creatine kinase myocardial band (CKMB) and creatine kinase (CK) peak levels. In the TO group, LCX served as the main IRA (52.0%), whereas in the Non-TO group, LAD was the predominant IRA (45.1%). Compared to the Non-TO group, OCT findings demonstrated that red thrombus/mixed thrombus was more common in the TO group, along with a lower occurrence of white thrombus (p < 0.001). The TO group exhibited a higher prevalence of STUMI (p = 0.001), whereas STDMI was more commonly observed in the Non-TO group (p = 0.001). NSTEMI presents as STUMI and STDMI distinct entities. Red thrombus/mixed thrombus in IRA often indicates occlusive lesions with STUMI on ECG. White thrombus suggests non-occlusive lesions with STDMI on ECG.


Subject(s)
Coronary Angiography , Coronary Thrombosis , Coronary Vessels , Electrocardiography , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , Predictive Value of Tests , Tomography, Optical Coherence , Humans , Male , Female , Retrospective Studies , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnostic imaging , Non-ST Elevated Myocardial Infarction/therapy , Aged , Coronary Thrombosis/diagnostic imaging , Coronary Thrombosis/pathology , Risk Factors , Coronary Vessels/diagnostic imaging , Coronary Vessels/physiopathology , Multivariate Analysis , Logistic Models , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/physiopathology , Coronary Circulation , Chi-Square Distribution , Odds Ratio
16.
Med Sci Monit ; 30: e943526, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38734884

ABSTRACT

BACKGROUND A significant number of atrial fibrillation (AF) recurrences occur after initial ablation, often due to pulmonary vein reconnections or triggers from non-pulmonary veins. MATERIAL AND METHODS Patients with paroxysmal AF who underwent radiofrequency catheter ablation for the first time were enrolled. Base on propensity score matching (1: 1 matching), 118 patients were selected for an optimized workflow for the radiofrequency catheter ablation of paroxysmal AF (OWCA) group and a conventional group. Comparative analysis of the acute and 12-month clinical outcomes was conducted. Moreover, an artificial intelligence analytics platform was used to evaluate the quality of pulmonary vein isolation (PVI) circles. RESULTS PVI was successfully achieved in all patients. Incidence of first-pass isolation of bilateral PVI circles was higher (P=0.009) and acute pulmonary vein reconnections was lower (P=0.027) in the OWCA group than conventional group. The OWCA group displayed a significant reduction in the number of fractured points (P<0.001), stacked points (P=0.003), and a greater proportion of cases in which the radiofrequency index achieved the target value (P=0.003). Additionally, the contact force consistently met the force over time criteria (P<0.001) for bilateral PVI circles in the OWCA group, accompanied by a shorter operation time (P=0.017). During the 12-month follow-up period, the OWCA group exhibited a higher atrial arrhythmia-free survival rate following the initial ablation procedure than did the conventional group. CONCLUSIONS The optimized workflow for radiofrequency catheter ablation of paroxysmal AF could play a crucial role in creating higher quality PVI circles. This improvement is reflected in a significantly elevated 12-month atrial arrhythmia-free survival rate.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Workflow , Humans , Atrial Fibrillation/surgery , Catheter Ablation/methods , Female , Male , Middle Aged , Treatment Outcome , Pulmonary Veins/surgery , Aged , Propensity Score , Recurrence
17.
Angew Chem Int Ed Engl ; 63(30): e202405639, 2024 07 22.
Article in English | MEDLINE | ID: mdl-38708791

ABSTRACT

The high level of lactate in tumor microenvironment not only promotes tumor development and metastasis, but also induces immune escape, which often leads to failures of various tumor therapy strategies. We here report a sono-triggered cascade lactate depletion strategy by using semiconducting polymer nanoreactors (SPNLCu) for cancer cuproptosis-immunotherapy. The SPNLCu mainly contain a semiconducting polymer as sonosensitizer, lactate oxidase (LOx) conjugated via a reactive oxygen species (ROS)-cleavable linker and chelated Cu2+. Upon ultrasound (US) irradiation, the semiconducting polymer generates singlet oxygen (1O2) to cut ROS-cleavable linker to allow the release of LOx that catalyzes lactate depletion to produce hydrogen peroxide (H2O2). The Cu2+ will be reduced to Cu+ in tumor microenvironment, which reacts with the produced H2O2 to obtain hydroxyl radical (⋅OH) that further improves LOx release via destroying ROS-cleavable linkers. As such, sono-triggered cascade release of LOx achieves effective lactate depletion, thus relieving immunosuppressive roles of lactate. Moreover, the toxic Cu+ induces cuproptosis to cause immunogenic cell death (ICD) for activating antitumor immunological effect. SPNLCu are used to treat both subcutaneous and deep-tissue orthotopic pancreatic cancer with observably enhanced efficacy in restricting the tumor growths. This study thus provides a precise and effective lactate depletion tactic for cancer therapy.


Subject(s)
Copper , Immunotherapy , Lactic Acid , Pancreatic Neoplasms , Polymers , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/therapy , Lactic Acid/chemistry , Lactic Acid/metabolism , Polymers/chemistry , Polymers/pharmacology , Copper/chemistry , Humans , Animals , Mice , Semiconductors , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/chemistry , Mixed Function Oxygenases/metabolism , Mixed Function Oxygenases/chemistry , Ultrasonic Waves , Cell Line, Tumor , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
18.
Angew Chem Int Ed Engl ; 63(30): e202401683, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-38719735

ABSTRACT

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

19.
Clin Transl Sci ; 17(5): e13823, 2024 May.
Article in English | MEDLINE | ID: mdl-38771157

ABSTRACT

This study aims to investigate the mechanism of platelet activation-induced thrombosis in patients with acute non-ST segment elevation myocardial infarction (NSTEMI) by detecting the expression of autophagy-associated proteins in platelets of patients with NSTEMI. A prospective study was conducted on 121 patients with NSTEMI who underwent emergency coronary angiography and optical coherence tomography. The participants were divided into two groups: the ST segment un-offset group (n = 64) and the ST segment depression group (n = 57). We selected a control group of 60 patients without AMI during the same period. The levels of autophagy-associated proteins and the expression of autophagy-associated proteins in platelets were measured using immunofluorescence staining and Western blot. In NSTEMI, the prevalence of red thrombus was higher in the ST segment un-offset myocardial infarction (STUMI) group, whereas white thrombus was more common in the ST segment depression myocardial infarction (STDMI) group. Furthermore, the platelet aggregation rate was significantly higher in the white thrombus group compared with the red thrombus group. Compared with the control group, the autophagy-related protein expression decreased, and the expression of αIIbß3 increased in NSTEMI. The overexpression of Beclin1 could activate platelet autophagy and inhibit the expression of αIIbß3. The results suggested that the increase in platelet aggregation rate in patients with NSTEMI may be potentially related to the change in autophagy. And the overexpression of Beclin1 could reduce the platelet aggregation rate by activating platelet autophagy. Our findings demonstrated that Beclin1 could be a potential therapeutic target for inhibiting platelet aggregation in NSTEMI.


Subject(s)
Autophagy , Beclin-1 , Blood Platelets , Non-ST Elevated Myocardial Infarction , Platelet Activation , Thrombosis , Humans , Beclin-1/metabolism , Male , Female , Non-ST Elevated Myocardial Infarction/blood , Middle Aged , Aged , Prospective Studies , Blood Platelets/metabolism , Thrombosis/blood , Thrombosis/metabolism , Coronary Angiography , Platelet Aggregation , Case-Control Studies , Tomography, Optical Coherence , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
20.
Front Plant Sci ; 15: 1371040, 2024.
Article in English | MEDLINE | ID: mdl-38742213

ABSTRACT

Introduction: Clonal fragmentation helps to assess clonal plants' growth resilience to human and environmental disturbance. Although clonal integration in epiphytes in tropical rubber plantations is important to understand their role in enhancing biodiversity and ecosystem services, research on this subject is limited. These plantations are typically monospecific economic forests that face increased anthropogenic disturbances. Methods: In this study, we selected the clonal fern Pyrrosia nuda to study its survival status, biomass, maximum quantum yield of photosystem II (Fv/Fm), and frond length in response to the level of clonal fragmentation in a tropical rubber plantation. Results and discussion: The results showed that (1) clonal fragmentation significantly negatively affected the survival rate, biomass, and frond length of clonal plants, but with minimal effects on Fv/Fm at different growth stages; (2) the performance of a ramet (e.g., biomass or frond length) increased with ramet developmental ages and decreased with the number of ramets in a clonal fragment. The age-dependent impacts of clonal fragmentation provide insights into the biodiversity conservation of epiphytes and forest management in man-made plantations. Therefore, to better conserve the biodiversity in tropical forests, especially in environment-friendly rubber plantations, there is a need to reduce anthropogenic disturbances and alleviate the level of fragmentation.

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