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1.
J Thorac Dis ; 16(4): 2379-2393, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38738238

RESUMO

Background: Data regarding the safety and efficacy of delayed completion lobectomy (CL) following sublobar resections remain scant. We evaluated the technical difficulty and short-term outcomes of CL occurring at least 3 months following the anatomical segmentectomy or wedge resection. Methods: Consecutive non-small cell lung cancer (NSCLC) patients who underwent a second resection within the same lobe at least 3 months after their initial resection from January 2013 to December 2019 at the Shanghai Pulmonary Hospital were retrospectively included. The patients were divided into a segmentectomy group (SG group) and a wedge resection group (WR group) based on their initial resection strategy. Baseline characteristics and short-term outcomes after CL between the two groups were compared. Results: Twenty-five patients undergoing CL were included, nine in the SG group and 16 in the WR group. No deaths occurred within 30 days postoperatively, and the rate of overall postoperative complications was 28.0% (7/25). Statistically significant differences were found in rates of postoperative complications between the two groups (SG: 55.6% vs. WR: 12.5%, P=0.03) and in the use of bronchoplasty or angioplasty during the CL (SG: 33.3% vs. WR: 0.0%, P=0.04). After CL, no significant differences were found in 5-year recurrence-free survival (RFS) (WR: 66.7% vs. SG: 61.0%, P=0.31) or overall survival (OS) (WR: 93.8% vs. SG: 66.7%, P=0.06) between two groups. Conclusions: Delayed CL occurring over 3 months after sublobar resection is a safe and effective procedure, with no deaths occurring within 30 days postoperatively. As compared to a segmentectomy at the time of the index operation, a wedge resection may portend less morbidity, with a decreased risk of needing adjunctive bronchoplasty or angioplasty procedures during CL. After CL, 5-year RFS and OS were comparable between WR and SG groups.

2.
Anal Chem ; 96(16): 6148-6157, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38603515

RESUMO

Photodynamic therapy (PDT) provides an alternative approach to targeted cancer treatment, but the therapeutic mechanism of advanced nanodrugs applied to live cells and tissue is still not well understood. Herein, we employ the hybrid hyperspectral stimulated Raman scattering (SRS) and transient absorption (TA) microscopy developed for real-time in vivo visualization of the dynamic interplay between the unique photoswichable lanthanide-doped upconversion nanoparticle-conjugated rose bengal and triphenylphosphonium (LD-UCNP@CS-Rb-TPP) probe synthesized and live cancer cells. The Langmuir pharmacokinetic model associated with SRS/TA imaging is built to quantitatively track the uptakes and pharmacokinetics of LD-UCNP@CS-Rb-TPP within cancer cells. Rapid SRS/TA imaging quantifies the endocytic internalization rates of the LD-UCNP@CS-Rb-TPP probe in individual HeLa cells, and the translocation of LD-UCNP@CS-Rb-TPP from mitochondria to cell nuclei monitored during PDT can be associated with mitochondria fragmentations and the increased nuclear membrane permeability, cascading the dual organelle ablations in cancer cells. The real-time SRS spectral changes of cellular components (e.g., proteins, lipids, and DNA) observed reflect the PDT-induced oxidative damage and the dose-dependent death pattern within a single live cancer cell, thereby facilitating the real-time screening of optimal light dose and illumination duration controls in PDT. This study provides new insights into the further understanding of drug delivery and therapeutic mechanisms of photoswitchable LD-UCNP nanomedicine in live cancer cells, which are critical in the optimization of nanodrug formulations and development of precision cancer treatment in PDT.


Assuntos
Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Células HeLa , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Análise Espectral Raman , Rosa Bengala/química , Rosa Bengala/farmacologia , Microscopia Óptica não Linear , Relação Dose-Resposta a Droga
4.
J Am Chem Soc ; 146(13): 9413-9421, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38506128

RESUMO

Precise control of cellular signaling events during programmed cell death is crucial yet challenging for cancer therapy. The modulation of signal transduction in cancer cells holds promise but is limited by the lack of efficient, biocompatible, and spatiotemporally controllable approaches. Here we report a photodynamic strategy that modulates both apoptotic and pyroptotic cell death by altering caspase-3 protein activity and the associated signaling crosstalk. This strategy employs a mitochondria-targeting, near-infrared activatable probe (termed M-TOP) that functions via a type-I photochemical mechanism. M-TOP is less dependent on oxygen and more effective in treating drug-resistant cancer cells, even under hypoxic conditions. Our study shows that higher doses of M-TOP induce pyroptotic cell death via the caspase-3/gasdermin-E pathway, whereas lower doses lead to apoptosis. This photodynamic method is effective across diverse gasdermin-E-expressing cancer cells. Moreover, the M-TOP mediated shift from apoptotic to pyroptotic modulation can evoke a controlled inflammatory response, leading to a robust yet balanced immune reaction. This effectively inhibits both distal tumor growth and postsurgical tumor recurrence. This work demonstrates the feasibility of modulating intracellular signaling through the rational design of photodynamic anticancer drugs.


Assuntos
Gasderminas , Neoplasias , Humanos , Caspase 3/metabolismo , Apoptose , Transdução de Sinais , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Caspase 8/metabolismo , Caspase 8/farmacologia , Caspase 1/metabolismo , Caspase 1/farmacologia
5.
Oncol Rep ; 51(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456498

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell invasion and migration assay data shown in Figs. 2C and 5D were strikingly similar to data in different form in other articles written by different authors at different research institutes, which had either already been published or had been submitted for publication at around the same time (some of which have now been retracted). Owing to the fact that certain of the data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 2329­2338, 2016; DOI: 10.3892/or.2016.5007].

6.
Diagn Pathol ; 19(1): 29, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341587

RESUMO

BACKGROUND: Cytotoxic lymphocytes (CLs) express potent toxins, including perforin (P) and granzyme-B (G), which brings about target cell death. The purpose of this study was to evaluate the killing capacity of tumor-infiltrating CLs by means of P and G analysis, and explore the association with lymph node metastasis in papillary carcinoma of thyroid (PTC) without Hashimoto's thyroiditis (HT). METHODS: Infiltration of lymphocytes in PTC was observed in frozen sections. Both fresh tumor tissues and paracancerous tissues with lymphocyte infiltration were collected and prepared into a single cell suspension. Flow cytometry was used to detect the percentages of CD3+P+, CD3+G+, CD8+P+, and CD8+G+ T lymphocytes (TLs) and CD16-CD56+P+ and CD16-CD56+G+ natural killer (NK) cells. Finally, we investigated differential expression of P and G in NK cells and cytotoxic T lymphocytes (CTLs) in paired tumor tissues (group T, n = 44) and paracancerous tissues (group N, n = 44) from patients with PTC with the BRAF V600E mutation. Furthermore, patients were divided into two groups according to whether cervical central lymph node metastasis (CCLNM) existed: group A (with lymph node metastases, n = 27) and group B (with nonlymph node metastases, n = 17). Patients were also divided into three groups according to the total number of positive CCLNM: group B, group C (with low-level lymph node metastases, less than 5, n = 17) and group D (with high-level lymph node metastases, no less than 5, n = 10). RESULTS: The percentage of CD3+P+ CTLs was significantly higher in group N than in group T (P < 0.05). The percentage of CD8+G+ CTLs was significantly higher in group T than in group N (P < 0.05). The percentages of CD3+G+, CD16-CD56+P+and CD16-CD56+G+ NK cells showed no significant difference in either group T or group N (P > 0.05). The percentages of CD3+P+ CTLs in group A and group C were significantly higher in the paracancerous tissue than in the tumor tissue (P < 0.05). The percentages of CD8+G+ CTLs in group A and group C were significantly higher in the tumor tissues than in the paracancerous tissues (P < 0.05). The percentage of CD16-CD56+G+ NK cells in group D was significantly higher in the tumor tissues than in the paracancerous tissues (P < 0.05). CONCLUSIONS: The killing capacity of infiltrating CLs in PTC differed between tumor tissues and paracancerous tissues. In cases with CCLNM, higher expression of CD16-CD56+G+ NK cells in tumor tissues may be associated with a high risk of lymph node metastasis.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Metástase Linfática , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias da Glândula Tireoide/patologia , Células Matadoras Naturais/patologia , Mutação
7.
Eur J Cardiothorac Surg ; 65(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341657

RESUMO

OBJECTIVES: Tracheoesophageal fistula (TEF) is characterized by abnormal connectivity between the posterior wall of the trachea or bronchus and the adjacent anterior wall of the oesophagus. Benign TEF can result in serious complications; however, there is currently no uniform standard to determine the appropriate surgical approach for repairing TEF. METHODS: The PubMed database was used to search English literature associated with TEF from 1975 to October 2023. We employed Boolean operators and relevant keywords: 'tracheoesophageal fistula', 'tracheal resection', 'fistula suture', 'fistula repair', 'fistula closure', 'flap', 'patch', 'bioabsorbable material', 'bioprosthetic material', 'acellular dermal matrix', 'AlloDerm', 'double patch', 'oesophageal exclusion', 'oesophageal diversion' to search literature. The evidence level of the literature was assessed based on the GRADE classification. RESULTS: Nutritional support, no severe pulmonary infection and weaning from mechanical ventilation were the 3 determinants for timing of operation. TEFs were classified into 3 levels: small TEF (<1 cm), moderate TEF (≥1 but <5 cm) and large TEF (≥5 cm). Fistula repair or tracheal segmental resection was used for the small TEF with normal tracheal status. If the anastomosis cannot be finished directly after tracheal segmental resection, special types of tracheal resection, such as slide tracheoplasty, oblique resection and reconstruction, and autologous tissue flaps were preferred depending upon the site and size of the fistula. Oesophageal exclusion was applicable to refractory TEF or patients with poor conditions. CONCLUSIONS: The review primarily summarizes the main surgical techniques employed to repair various acquired TEF, to provide references that may contribute to the treatment of TEF.


Assuntos
Procedimentos de Cirurgia Plástica , Fístula Traqueoesofágica , Humanos , Fístula Traqueoesofágica/cirurgia , Fístula Traqueoesofágica/etiologia , Traqueia/cirurgia , Retalhos Cirúrgicos/cirurgia
8.
Nat Mater ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191632

RESUMO

High-sensitivity radiation detectors for energetic particles are essential for advanced applications in particle physics, astronomy and cancer therapy. Current particle detectors use bulk crystals, and thin-film organic scintillators have low light yields and limited radiation tolerance. Here we present transmissive thin scintillators made from CsPbBr3 nanocrystals, designed for real-time single-proton counting. These perovskite scintillators exhibit exceptional sensitivity, with a high light yield (~100,000 photons per MeV) when subjected to proton beams. This enhanced sensitivity is attributed to radiative emission from biexcitons generated through proton-induced upconversion and impact ionization. These scintillators can detect as few as seven protons per second, a sensitivity level far below the rates encountered in clinical settings. The combination of rapid response (~336 ps) and pronounced ionostability enables diverse applications, including single-proton tracing, patterned irradiation and super-resolution proton imaging. These advancements have the potential to improve proton dosimetry in proton therapy and radiography.

9.
Nano Lett ; 24(8): 2503-2510, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38258747

RESUMO

X-ray scintillators have utility in radiation detection, therapy, and imaging. Various materials, such as halide perovskites, organic illuminators, and metal clusters, have been developed to replace conventional scintillators due to their ease of fabrication, improved performance, and adaptability. However, they suffer from self-absorption, chemical instability, and weak X-ray stopping power. Addressing these limitations, we employ alkali metal doping to turn nonemissive CsPb2Br5 into scintillators. Introducing alkali metal dopants causes lattice distortion and enhances electron-phonon coupling, which creates transient potential energy wells capable of trapping photogenerated or X-ray-generated electrons and holes to form self-trapped excitons. These self-trapped excitons undergo radiative recombination, resulting in a photoluminescence quantum yield of 55.92%. The CsPb2Br5-based X-ray scintillator offers strong X-ray stopping power, high resistance to self-absorption, and enhanced stability when exposed to the atmosphere, chemical solvents, and intense irradiation. It exhibits a detection limit of 162.3 nGyair s-1 and an imaging resolution of 21 lp mm-1.

10.
Angew Chem Int Ed Engl ; 63(10): e202319853, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38242857

RESUMO

Developing fluorogenic probes for simultaneous live cell labeling of multiple targets is crucial for understanding complex cellular events. The emerging [4+1] cycloaddition between tetrazine and isonitriles holds promise as a bioorthogonal tool, yet existing tetrazine probes lack reactivity and fluorogenicity. Here, we present the development of a series of tetrazine-functionalized bioorthogonal probes. By incorporating pyrazole adducts into the fluorophore scaffolds, the post-reacted probes displayed remarkable fluorescence turn-on ratios, up to 3184-fold. Moreover, these modifications are generalizable to various fluorophores, enabling a broad emission range from 473 to 659 nm. Quantum chemical calculations further elucidate the turn-on mechanisms. These probes enable the simultaneous labeling of multiple targets in live cells, without the need for a washing step. Consequently, our findings pave the way for advanced multiplex imaging and detection techniques for cellular studies.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Linhagem Celular Tumoral , Reação de Cicloadição , Imagem Óptica/métodos
11.
Adv Sci (Weinh) ; 11(7): e2305761, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063803

RESUMO

Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited-state properties. Herein, a synthetic approach for attaching aryl substituents at the C2' position of the thio-pentamethine cyanine (TCy5) dye structure is reported for the first time. C2'-aryl substitution enables the regulation of both the twisted intramolecular charge transfer (TICT) and photoinduced electron transfer (PET) mechanisms to be regulated in the excited state. Modulation of these mechanisms allows the design of a nitroreductase-activatable TCy5 fluorophore for hypoxic tumor photodynamic therapy and fluorescence imaging. These C2'-aryl TCy5 dyes provide a tunable platform for engineering cyanine dyes tailored to sophisticated biological applications, such as photodynamic therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes , Corantes Fluorescentes/química , Imagem Óptica/métodos
12.
Artigo em Inglês | MEDLINE | ID: mdl-37930040

RESUMO

OBJECTIVES: To provide the experience of surgical treatment for bronchiectasis-destroyed lung (BDL) and evaluate the feasibility of video-assisted thoracoscopic surgery (VATS). METHODS: BDL patients underwent surgical treatment between January 2013 and June 2018 were included. Logistic regression was performed to assess factors for major complications, and Cox's regression was performed to assess factors affected symptomatic outcome. RESULTS: Totally, 143 patients were treated by VATS (n = 64) and thoracotomy (n = 79). Nine (14.1%) cases scheduled for VATS were converted to thoracotomy for dense adhesions (n = 6) and frozen hilum (n = 3). The VATS group had a median chest tube duration, hospitalization and a time of returning to full activity of 4 days, 5 days and 1.5 months, respectively. Major complications occurred in 28 (19.6%) of all patients, 50.0% after pneumonectomy and 13.4% after lobectomy/extensive lobectomy. Multivariable analysis identified pneumonectomy [odds ratio, 3.64; 95% confidence interval (CI), 1.18-11.21] as a significant predictor for major complications. Overall, 141 (98.6%) patients benefitted from surgery (completely asymptomatic, n = 109; acceptable alleviation, n = 32). Thirty-four patients experienced relapse of the disease, including 13 with productive cough, 11 with haemoptysis and 10 with recurrent infections. Pseudomonas aeruginosa infection [hazard ratio (HR), 3.07; 95% CI, 1.38-6.83] and extent of remanent bronchiectatic areas (HR, 1.03; 95% CI, 1.00-1.05) were independent risk factors for shorter relapse free interval. CONCLUSIONS: VATS for BDL is feasible in well-selected patients. Pneumonectomy increased the risk of postoperative major complications. Removing all BDL lesions contributed to satisfactory prognosis.

13.
Food Chem X ; 19: 100807, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37780243

RESUMO

This study evaluated the effects of hot air drying (HAD), microwave drying (MD), vacuum drying (VD), sun drying (SD) and vacuum freeze drying (VFD) on the physical properties, bioactive components, antioxidant capacity, volatile components and industrial application of coffee peel. The results showed VFD could retain the appearance color, total phenolics (19.49 mg GAE/g DW), total flavonoids (9.65 mg CE/g DW), caffeine (3.15 mg/g DW), trigonelline (2.71 mg/g DW), and antioxidant capacities of fresh sample to the greatest extent, but its operating cost was significantly higher than other treatments and total volatile components were in the minimum levels. HAD and SD exhibited the highest loss rates of total phenols and antioxidant capacities, exceeding 50%. MD offered the lowest operating cost, superior retention of bioactive components, and the richest variety and quantity of volatile compounds. Therefore, it is recommended to use MD to dehydrate the coffee peel in actual production.

14.
Nat Immunol ; 24(11): 1813-1824, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37813965

RESUMO

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.


Assuntos
Citofagocitose , Células de Kupffer , Humanos , Fagocitose/genética , Galectinas/genética , Galectinas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
15.
Biosens Bioelectron ; 242: 115716, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37820557

RESUMO

Supramolecular chemistry offers new insights in bioimaging, but specific tracking of enzyme in living cells via supramolecular host-guest reporter pair remains challenging, largely due to the interference caused by the complex cellular environment on the binding between analytes and hosts. Here, by exploiting the principle of supramolecular tandem assay (STA) and the classic host-guest reporter pair (p-sulfonatocalix[4]arene (SC4A) and lucigenin (LCG)) and rationally designing artificial peptide library to screen sequence with high affinity of the target enzyme, we developed a "turn-on" fluorescent sensing system for intracellular imaging of histone deacetylase 1 (HDAC1), which is a potential therapeutic target for various diseases, including cancer, neurological, and cardiovascular diseases. Based on computational simulations and experimental validations, we verified that the deacetylated peptide by HDAC1 competed LCG, freeing it from the SC4A causing fluorescence increase. Enzyme kinetics experiments were further conducted to prove that this assay could detect HDAC1 specifically with high sensitivity (the LOD value is 0.015 µg/mL, ten times lower than the published method). This system was further applied for high-throughput screening of HDAC1 inhibitors over a natural compound library containing 147 compounds, resulting in the identification of a novel HDAC1 down-regulator (Ginsenoside RK3). Our results demonstrated the sensitivity and robustness of the assay system towards HDAC1. It should serve as a valuable tool for biochemical studies and drug screening.


Assuntos
Técnicas Biossensoriais , Histona Desacetilase 1 , Histona Desacetilase 1/metabolismo , Ensaios de Triagem em Larga Escala , Inibidores de Histona Desacetilases/farmacologia , Peptídeos
16.
ACS Appl Mater Interfaces ; 15(32): 38230-38246, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37535406

RESUMO

Morbid dermal templates, microangiopathy, and abnormal inflammation are the three most critical reasons for the scarred healing and the high recurrence rate of diabetic wounds. In this present study, a combination of a methacrylated decellularized extracellular matrix (ECMMA, aka EM)-based hydrogel system loaded with copper-epigallocatechin gallate (Cu-EGCG) capsules is proposed to fabricate bio-printed dermal scaffolds for diabetic wound treatment. Copper ions act as a bioactive element for promoting angiogenesis, and EGCG can inhibit inflammation on the wound site. In addition to the above activities, EM/Cu-EGCG (E/C) dermal scaffolds can also provide optimized templates and nutrient exchange space for guiding the orderly deposition and remodeling of ECM. In vitro experiments have shown that the E/C hydrogel can promote angiogenesis and inhibit the polarization of macrophages to the M1 pro-inflammatory phenotype. In the full-thickness skin defect model of diabetic rats, the E/C dermal scaffold combined with split-thickness skin graft transplantation can alleviate pathological scarring via promoting angiogenesis and driving macrophage polarization to the anti-inflammatory M2 phenotype. These may be attributed to the scaffold-actuated expression of angiogenesis-related genes in the HIF-1α/vascular endothelial growth factor pathway and decreased expression of inflammation-related genes in the TNF-α/NF-κB/MMP9 pathway. The results of this study show that the E/C dermal scaffold could serve as a promising artificial dermal analogue for solving the problems of delayed wound healing and reulceration of diabetic wounds.


Assuntos
Cicatriz , Diabetes Mellitus Experimental , Ratos , Animais , Cobre/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Inflamação , Hidrogéis/farmacologia , Impressão Tridimensional
17.
Artigo em Inglês | MEDLINE | ID: mdl-37572305

RESUMO

Management of large tracheoesophageal fistulas complicated by tracheal stenosis remains challenging as it requires an ideal replacement for the membranous defect as well as a permanent buttress to reconstruct the stenotic segment. We present the successful use of an autologous free dermal flap reinforced with a pedicled pectoralis major muscle to repair the tracheal membranous wall and a rib cartilage graft to enlarge the tracheal lumen.

18.
Adv Mater ; 35(44): e2303567, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37466394

RESUMO

The metabolic reprogramming of glioblastoma (GBM) poses a tremendous obstacle to effective immunotherapy due to its impact on the immunosuppressive microenvironment. In this work, a hydrogen-bonded organic framework (HOF) specifically designed for GBM immunotherapy is developed, taking advantage of the relatively isolated cholesterol metabolism microenvironment in the central nervous system (CNS). The HOF-based biotuner regulates extra/intracellular cholesterol metabolism, effectively blocking the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway and reducing 2B4 expression. This metabolically disrupts the immunosuppressive microenvironment of GBM and rejuvenates CD8+ T cells. Moreover, cholesterol metabolism regulation offers additional benefits in treating GBM invasion. Furthermore, tumor microenvironment (TME)-initiated chemiexcited photodynamic therapy (PDT) is enhanced during the regulation of cholesterol metabolism, and the biotuner can effectively trigger immunogenic cell death (ICD) and increase the infiltration of cytotoxic T lymphocytes (CTLs) in GBM. By reversing the immunosuppressive microenvironment and bolstering chemiexcited-PDT, this approach invigorates efficient antibody non-dependent immunotherapy for GBM. This study provides a model for enhancing immunotherapy through cholesterol metabolism regulation and explores the feasibility of a "metabolic checkpoint" strategy in GBM treatment.


Assuntos
Glioblastoma , Humanos , Glioblastoma/patologia , Linfócitos T CD8-Positivos/metabolismo , Imunoterapia , Linfócitos T Citotóxicos , Anticorpos/uso terapêutico , Microambiente Tumoral
19.
Angew Chem Int Ed Engl ; 62(32): e202307797, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37336786

RESUMO

Photoacoustic imaging (PAI), a state-of-the-art noninvasive in vivo imaging technique, has been widely used in clinical disease diagnosis. However, the design of high-performance PAI agents with three key characteristics, i.e., near-infrared (NIR) absorption (λabs >800 nm), intense PA signals, and excellent photostability, remains a challenging goal. Herein, we present a facile but effective approach for engineering PAI agents by amplifying intramolecular low-frequency vibrations and enhancing the push-pull effect. As a demonstration of this blended approach, we constructed a PAI agent (BDP1-NEt2 ) based on the boron-dipyrromethene (BODIPY) scaffold. Compared with indocyanine green (ICG, an FDA-approved organic dye widely utilized in PAI studies; λabs =788 nm), BDP1-NEt2 exhibited a UV/Vis-NIR spectrum peaked at 825 nm, superior in vivo PA signal intensity and outstanding stability to offer improved tumor diagnostics. We believe this work provides a promising strategy to develop the next generation of PAI agents.


Assuntos
Técnicas Fotoacústicas , Técnicas Fotoacústicas/métodos , Vibração , Verde de Indocianina , Corantes , Diagnóstico por Imagem
20.
ACS Appl Mater Interfaces ; 15(19): 22967-22976, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37145981

RESUMO

In this research, we developed a photoluminescent platform using amine-coupled fluorophores, generated from a single conjugate acceptor containing bis-vinylogous thioesters. Based on the experimental and computational results, the fluorescence turn-on mechanism was proposed to be charge separated induced energy radiative transition for the amine-coupled fluorophore, while the sulfur-containing precursor was not fluorescent since the energy internal conversion occurred through vibrational 2RS- (R represents alkyl groups) as energy acceptor(s). Further utilizing the conjugate acceptor, we establish a new fluorogenic approach via a highly cross-linked soft material to selectively detect cysteine under neutral aqueous conditions. Turn-on fluorescence emission and macroscopic degradation occurred in the presence of cysteine as the stimuli, which can be visually tracked due to the generation of an optical indicator and the cleavage of linkers within the matrix. Furthermore, a novel drug delivery system was constructed, achieving controlled release of sulfhydryl drug (6-mercaptopurine) which was tracked by photoluminescence and high-performance liquid chromatography. The photoluminescent molecules developed herein are suitable for visualizing polymeric degradation, making them suitable for additional "smart" material applications.


Assuntos
Polímeros Responsivos a Estímulos , Compostos de Sulfidrila , Compostos de Sulfidrila/química , Cisteína , Liberação Controlada de Fármacos , Aminas , Corantes Fluorescentes/química
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