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1.
BMC Gastroenterol ; 24(1): 340, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354347

RESUMO

BACKGROUND: Drug-coated balloons (DCBs) angioplasty is safe and effective for coronary artery disease. However, DCBs dilatation for the treatment of benign esophageal strictures is rarely reported. PURPOSE: We aimed to report the clinical outcomes of DCBs dilatation for patients with benign esophageal strictures. METHODS: From May 2020 to August 2023, 18 patients underwent DCBs dilatation for benign esophageal strictures. Baseline demographics were recorded and evaluated, including gender, age, comorbidities, stricture diameter and length, dilatation session, complications. RESULTS: A total of 24 dilatation sessions of DCBs were performed, with a mean of 1.3 ± 0.6 sessions per patients (range 1.0-5.0). Dysphagia score decreased significantly after DCBs dilatation (2.6 ± 1.1 vs. 0.9 ± 1.3, p = 0.0002). Both stricture diameter and stricture index decreased significantly after DCBs dilatation (p < 0.0001). No procedure-related death, massive bleeding or esophageal perforation was observed during or after DCBs dilatation. Minor complications were found in only 3 patients (16.7%). All 18 patients were successfully followed up for a median period of 12.0 months. By the end of follow up, 10 patients showed no dysphagia, 6 patients showed mild dysphagia and 2 patients showed no improvement in dysphagia. The clinical success rate of DCBs dilatation is 88.9%. CONCLUSION: DCBs dilatation may be a safe, effective and feasible treatment for benign esophageal strictures, and can be utilized as an alternative option after standard dilatation has failed. Prospective studies with large samples are needed to further validate its clinical efficacy.


Assuntos
Transtornos de Deglutição , Dilatação , Estenose Esofágica , Humanos , Estenose Esofágica/terapia , Estenose Esofágica/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Dilatação/métodos , Dilatação/instrumentação , Resultado do Tratamento , Transtornos de Deglutição/terapia , Transtornos de Deglutição/etiologia , Estudos Retrospectivos , Materiais Revestidos Biocompatíveis , Adulto , Angioplastia com Balão/métodos , Idoso de 80 Anos ou mais
2.
Environ Sci Technol ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258979

RESUMO

The escalating utilization of carbon dots (CDs) in agriculture raises ecological concerns. However, their combined toxicity with arsenic remains poorly understood. Herein, we investigated the combined mitochondrial genotoxicity of CDs and arsenate at environmentally relevant concentrations across successive earthworm generations. Iron-doped CDs (CDs-Fe) strongly bound to arsenate and arsenite, while nitrogen-doped CDs (CDs-N) exhibited weaker binding. Both CDs enhanced arsenate bioaccumulation without affecting its biotransformation, with most arsenate being reduced to arsenite. CDs-Fe generated significantly more reactive oxygen species than did CDs-N, causing stronger mitochondrial DNA (mtDNA) damage. Arsenate further exacerbated the oxidative mtDNA damage induced by CDs-N, as evidenced by increased reactive oxygen species, elevated 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) levels, and a higher correlation between 8-OHdG and mtDNA damage. This was due to arsenic inhibiting the antioxidant enzyme catalase. This exacerbation was negligible with CDs-Fe because their strong binding with arsenic prevented catalase inhibition. Maternal mitochondrial DNA damage was inherited by filial earthworms, which experienced significant weight loss in coexposure groups coupled with mtDNA toxicity. This study reveals the synergistic genotoxicity of CDs and arsenate, suggesting that CDs could disrupt the arsenic biogeochemical cycle, increase arsenate risk to terrestrial animals, and influence ecosystem stability and health through multigenerational impacts.

3.
Quant Imaging Med Surg ; 14(9): 6352-6361, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39281158

RESUMO

Background: Airway obstruction due to tumor invasion or concurrent respiratory distress and hemoptysis poses a significant challenge in clinical management, often requiring prompt and effective intervention to alleviate symptoms and improve patient outcomes. This study aimed to evaluate the efficacy and safety of selective transcatheter arterial embolization (TAE) as a preparatory measure to mitigate airway obstruction before bronchoscopic debulking as an approach to address this clinical challenge. Methods: The data of patients with airway obstruction due to tumor invasion or concurrent respiratory distress and hemoptysis treated at The First Affiliated Hospital of Zhengzhou University from January 2018 to August 2022 were analyzed. After computed tomography (CT) scans and bronchoscopic findings were assessed, selective TAE was performed as a preparatory measure to alleviate airway obstruction before bronchoscopic debulking, and the occurrence of hemorrhage-related complications, Karnofsky Performance Status (KPS) score, breathlessness index, and the extent of airway obstruction were evaluated. Results: All 22 patients underwent selective TAE before bronchoscopic tumor debulking. The overall efficacy rate was 100%, with a significant improvement in the KPS score from preoperative (60.45±14.63) to postoperative (74.55±9.63) levels (t=-6.891; P<0.001). Similarly, there was a considerable reduction in the shortness of breath score from preoperative (2.91±0.81) to postoperative (1.73±0.63) levels (t=6.973; P<0.001). Airway obstruction decreased substantially from preoperative (79.14%±14.56%) to postoperative (21.27%±7.19%) levels (t=26.857; P<0.001). Furthermore, the severity classification of airway obstruction decreased from preoperative (4±0.82) to postoperative (1.36±0.49) levels (t=18.794; P<0.001). Among the patients, only one experienced moderate bleeding necessitating prolonged mechanical balloon compression and intracavitary lesion removal, while the other patients had minor and negligible bleeding. Conclusions: TAE combined with endoscopic debulking can effectively control intraoperative bleeding and respiratory distress and achieve successful local resolution of endotracheal hypervascular tumors.

4.
Anal Chem ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138138

RESUMO

The accurate identification of energetic heterocyclic compounds (EHCs) is of great significance in munition assessment, environmental monitoring, and biosafety but remains largely underexplored. Herein, a covalent organic frameworks-based fluorescence sensor array (COFx sensor array) for efficient screening of EHCs is reported. The topologies of the COFs were rationally designed by modulating the pore sizes and linkage strategies to achieve the simplified sensor array. Eighteen EHC representatives, including single-, dual-, and three-ring EHCs with multivariate substructures, were successfully discriminated ranging from 10 µM to 1 mM. The sensor array showed robust selectivity against a wide range of interferences. The quantitative structure-activity relationship (QSAR) analysis has been conducted for the mechanistic study of the sensor array. Three multiple linear regression models have been established using molecular descriptors to evaluate and predict Stern-Volmer coefficient values, achieving explicit correlation between EHC structures and the signal outputs of the sensor array. Five molecular descriptors are retained to reveal the governing factors of the sensor array resolution. The QSAR analysis facilitates the design and development of the COFx sensor array, offering a new approach for customized multivariate analysis.

5.
Angew Chem Int Ed Engl ; 63(41): e202407928, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39022842

RESUMO

Although highly appealing for rapid access of molecular complexity, multi-functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp3)-H functionalization, thus enabling a smooth 1,2,5-trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring-opening process, which is followed by a series of 1,5-hydrogen atom transfer (1,5-HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site-selective introduction of three different functional groups is accomplished and a broad spectrum of valuable ß-hydroxyl-ϵ-fluoro-nitrile products are synthesized from readily available terminal alkenes.

6.
Eur J Cardiothorac Surg ; 66(2)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38980196

RESUMO

OBJECTIVES: Our objective was to explore the safety and efficacy of a graphene oxide-loaded rapamycin-coated self-expandable metallic airway stent (GO@RAPA-SEMS) in a rabbit model. METHODS: The dip coating method was used to develop a GO@RAPA-SEMS and a poly(lactic-co-glycolic)-acid loaded rapamycin-coated self-expandable metallic airway stent (PLGA@RAPA-SEMS). The surface structure was evaluated using a scanning electronic microscope. The in vitro drug-release profiles of the 2 stents were explored and compared. In the animal study, a total of 45 rabbits were randomly divided into 3 groups and underwent 3 kinds of stent placements. Computed tomography was performed to evaluate the degree of stenosis at 1, 2 and 3 months after the stent operation. Five rabbits in each group were sacrificed after the computed tomography scan. The stented trachea and blood were collected for further pathological analysis and laboratory testing. RESULTS: The in vitro drug-release study revealed that GO@RAPA-SEMS exhibited a sudden release on the first day and maintained a certain release rate on the 14th day. The PLGA@RAPA-SEMS exhibited a longer sustained release time. All 45 rabbits underwent successful stent placement. Pathological results indicated that the granulation tissue thickness in the GO@RAPA-SEMS group was less than that in the PLGA@RAPA-SEMS group. The TUNEL and hypoxia-inducible factor-1α staining results support the fact that the granulation inhibition effect in the GO@RAPA-SEMS group was greater than that in the PLGA@RAPA-SEMS group. CONCLUSIONS: GO@RAPA-SEMS effectively inhibited stent-related granulation tissue hyperplasia.


Assuntos
Stents Farmacológicos , Tecido de Granulação , Grafite , Sirolimo , Animais , Coelhos , Grafite/administração & dosagem , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Tecido de Granulação/efeitos dos fármacos , Tecido de Granulação/patologia , Hiperplasia/prevenção & controle , Stents Metálicos Autoexpansíveis , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Materiais Revestidos Biocompatíveis , Modelos Animais de Doenças , Traqueia/efeitos dos fármacos , Traqueia/patologia
7.
Nucleic Acids Res ; 52(15): e67, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-38922685

RESUMO

Detecting multiple targets in living cells is important in cell biology. However, multiplexed fluorescence imaging beyond two-to-three targets remains a technical challenge. Herein, we introduce a multiplexed imaging strategy, 'sequential Fluorogenic RNA Imaging-Enabled Sensor' (seqFRIES), which enables live-cell target detection via sequential rounds of imaging-and-stripping. In seqFRIES, multiple orthogonal fluorogenic RNA aptamers are genetically encoded inside cells, and then the corresponding cell membrane permeable dye molecules are added, imaged, and rapidly removed in consecutive detection cycles. As a proof-of-concept, we have identified in this study four fluorogenic RNA aptamer/dye pairs that can be used for highly orthogonal and multiplexed imaging in living bacterial and mammalian cells. After further optimizing the cellular fluorescence activation and deactivation kinetics of these RNA/dye pairs, the whole four-color semi-quantitative seqFRIES process can be completed in ∼20 min. Meanwhile, seqFRIES-mediated simultaneous detection of critical signalling molecules and mRNA targets was also achieved within individual living cells. We expect our validation of this new seqFRIES concept here will facilitate the further development and potential broad usage of these orthogonal fluorogenic RNA/dye pairs for multiplexed and dynamic live-cell imaging and cell biology studies.


Assuntos
Aptâmeros de Nucleotídeos , Corantes Fluorescentes , Aptâmeros de Nucleotídeos/química , Corantes Fluorescentes/química , Humanos , Imagem Óptica/métodos , RNA/química , RNA/metabolismo
8.
ACS Appl Mater Interfaces ; 16(21): 27511-27522, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38752668

RESUMO

Electron transfer is considered to be a typical parameter that affects the catalytic activity of nanozymes. However, there is still controversy regarding whether higher or lower electron transfer numbers are beneficial for improving the catalytic activity of nanozymes. To address this issue, we propose the introduction of Pd doping as an important electron regulation strategy to tune electron transfer between Pt and ZIF-8 carriers (PtxPd1@ZIF-8). We observe a volcano-shaped relationship between the electron transfer number and catalytic activity, reaching its peak at Pt4Pd1@ZIF-8. Mechanism studies indicate that as the electron transfer number from Pt to ZIF-8 carriers increases, the d-band center of the active site Pt increases, reducing the occupancy of antibonding states and enhancing the adsorption capacity of the key intermediate (*O). However, a further increase in the adsorption of *O energy makes it difficult to desorb and participate in the next reaction, thus exhibiting volcanic activity. The optimized Pt4Pd1@ZIF-8 nanozyme is applied to develop an immunoassay for the detection of zearalenone, achieving a detection limit of 0.01 µg/L, which is 6 times higher than that of the traditional enzyme-linked immunosorbent assay. This work not only reveals the potential regulatory mechanism of electron transfer on the catalytic activity of nanozymes but also improves the performance of nanozyme-based biosensors.


Assuntos
Estruturas Metalorgânicas , Paládio , Platina , Catálise , Platina/química , Paládio/química , Estruturas Metalorgânicas/química , Transporte de Elétrons , Imunoensaio/métodos
10.
J Am Chem Soc ; 146(7): 4402-4411, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38329936

RESUMO

Fluorogenic RNA aptamers are valuable tools for cell imaging, but they still suffer from shortcomings such as easy degradation, limited photostability, and low fluorescence enhancement. Molecular crowding conditions enable the stabilization of the structure, promotion of folding, and improvement of activity of functional RNA. Based on artificial RNA condensates, here we present a versatile platform to improve fluorogenic RNA aptamer properties and develop sensors for target analyte imaging in living cells. Using the CUG repeat as a general tag to drive phase separation, various fluorogenic aptamer-based RNA condensates (FLARE) were prepared. We show that the molecular crowding of FLARE can improve the enzymatic resistance, thermostability, photostability, and binding affinity of fluorogenic RNA aptamers. Moreover, the FLARE systems can be modularly engineered into sensors (FLARES), which demonstrate enhanced brightness and sensitivity compared to free sensors dispersed in homogeneous solution. This scalable design principle provides new insights into RNA aptamer property regulation and cellular imaging.


Assuntos
Aptâmeros de Nucleotídeos , RNA , RNA/química , Aptâmeros de Nucleotídeos/química , Corantes Fluorescentes/química , Fluorescência
11.
ACS Sens ; 9(2): 1023-1030, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38353664

RESUMO

The development of highly sensitive and selective analytical approaches for monitoring enzymatic activity is critical for disease diagnosis and biomedical research. Herein, we develop an exogenous co-reactant-free electrochemiluminescence (ECL) biosensor for the ratiometric measurement of α-glucosidase (α-Glu) based on a zeolitic imidazolate framework (ZIF-67)-regulated pyrene-based hydrogen-bonded organic framework (HOF-101). Target α-Glu can hydrolyze maltose to α-d-glucose, which can subsequently react with GOx to produce gluconic acid. The resultant gluconic acid can dissolve ZIF-67, leading to the recovery of the HOF-101 cathodic ECL signal and the decrease of the luminol anodic ECL signal. The long-range ordered structure of HOF-101 can speed up charge transfer, resulting in a stable and strong cathodic ECL signal. Moreover, ZIF-67 can not only efficiently quench the ECL signal of HOF-101 due to ECL resonance energy transfer between HOF-101 and ZIF-67 as well as the steric hindrance effect of ZIF-67 but also enhance the anodic ECL emission of luminol in dissolved O2 system because of its ordered and porous crystalline structure and the atomically dispersed Co2+. Notably, HOF-101 possesses a higher ECL efficiency (32.22%) compared with the Ru(bpy)32+ standard. Importantly, this ratiometric ECL biosensor shows high sensitivity (a detection limit of 0.19 U L-1) and a broad linear range (0.2-50 U L-1). This biosensor can efficiently eliminate systematic errors and enhance detection reliability without the involvement of exogenous co-reactants, and it displays good assay performance in human serum samples, holding great promise in biomedical research studies.


Assuntos
Técnicas Biossensoriais , Gluconatos , alfa-Glucosidases , Humanos , Medições Luminescentes/métodos , Reprodutibilidade dos Testes , Luminol , Técnicas Biossensoriais/métodos
12.
J Orthop Translat ; 44: 114-124, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38304614

RESUMO

Background: Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there is still a lack of therapy that can modify OA progression due to the complex pathogenic mechanisms. The aim of the study was to explore the role and mechanism of XJB-5-131 inhibiting chondrocytes ferroptosis to alleviate OA progression. Methods: We treated tert-butyl hydroperoxide (TBHP)-induced ferroptosis of mouse primary chondrocytes with XJB-5-131 in vitro. The intracellular ferroptotic hallmarks, cartilage anabolic and catabolic markers, ferroptosis regulatory genes and proteins were detected. Then we established a mouse OA model via destabilization of the medial meniscus (DMM) surgery. The OA mice were treated with intra-articular injection of XJB-5-131 regularly (2 µM, 3 times per week). After 4 and 8 weeks, we performed micro-CT and histological examination to evaluate the protection role of XJB-5-131 in mouse OA subjects. RNA sequencing analysis was performed to unveil the key downstream gene of XJB-5-131 exerting the anti-ferroptotic effect in OA. Results: XJB-5-131 significantly suppressed TBHP-induced increases of ferroptotic hallmarks (ROS, lipid peroxidation, and Fe2+ accumulation), ferroptotic drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored the expression of ferroptotic suppressors (Gpx4, Fth1). XJB-5-131 evidently promoted the expression of cartilage anabolic and decreased the expression of cartilage catabolic markers. Moreover, intra-articular injection of XJB-5-131 significantly inhibited the expression of Cox2 and Mmp13, while promoted the expression of Col2a1, Gpx4 and Fth1 in DMM-induced mouse articular cartilage. Further, we identified Pebp1 as a potential target of XJB-5-131 by RNA sequencing analysis. The anti-ferroptosis and chondroprotective effects of XJB-5-131 were significantly diminished by Locostatin, a specific antagonist of Pebp1. Conclusion: XJB-5-131 significantly protects chondrocytes from ferroptosis in TBHP-induced mouse primary chondrocytes and DMM surgery-induced OA mice model via restoring the expression of Pebp1. XJB-5-131 is a potential therapeutic drug in the management of OA progression.

13.
Food Chem ; 445: 138716, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38359573

RESUMO

Herein, we develop a dual-mode biosensor for photoelectrochemical and colorimetric detection of organophosphate pesticides (OPPs) based on ultrathin-FeOOH-coated MnO2 (MO@FHO) nanozyme. In this biosensor, OPPs can inhibit the alkaline phosphatase (ALP) activity and hinder the dephosphorylation of l-ascorbic acid-2-phosphate, preventing the decomposition of MO@FHO nanozyme and inducing both a photoelectrochemical (PEC) signal and the colorimetric change. The MO@FHO nanozyme not only possesses an enhanced catalase-like activity to degrade H2O2 for the generation of an improved cathodic photocurrent, but also exhibits an excellent oxidase-like activity to oxidize 3,3,5,5-tetramethylbenzidine with high catalytic efficiency. This biosensor displays a detection limit of 50 pmol/L for the PEC mode and a detection limit of 0.8 nmol/L for the colorimetric mode. Moreover, this biosensor exhibits excellent performance in complex biological matrices, and the smartphone-based visual sensing platform facilitates rapid and sensitive detection of OPPs, holding promising applications in food safety monitoring, and on-site detection.


Assuntos
Técnicas Biossensoriais , Inseticidas , Praguicidas , Catalase , Compostos Organofosforados , Colorimetria , Peróxido de Hidrogênio , Compostos de Manganês , Óxidos
14.
Mater Today Bio ; 24: 100927, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38234462

RESUMO

Transarterial chemoembolization (TACE) is a first-line treatment for intermediate to advanced-stage liver cancer, with drug-eluting microspheres commonly used as embolic agents. However, currently available drug-eluting microspheres suffer from low drug-loading capacity and limited drug options. In this work, we developed polydopamine-modified polyvinyl alcohol dual-drug-loaded microspheres encapsulating celecoxib and cisplatin (referred to as PCDMS). Physicochemical characterization revealed that the surface of the microspheres displayed increased roughness after polydopamine modification, and celecoxib and cisplatin were successfully loaded onto the microsphere surface. In vitro cell experiments demonstrated that the PCDMS significantly inhibited the proliferation and migration of highly metastatic human liver cancer cells (MHCC-97H) and human liver cancer cells (SMMC-7721). Furthermore, the dual-loaded microspheres exhibited remarkable tumor growth inhibition and reshaped the tumor microenvironment in both subcutaneous H22 liver cancer model in Balb/c mice and intrahepatic VX2 tumor model in New Zealand rabbits, demonstrating a synergistic antitumor effect where 1 + 1>2. This work provides a potential therapeutic approach for the treatment of refractory liver cancer and holds significant translational potential.

15.
Sci Rep ; 14(1): 2551, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38291135

RESUMO

Most patients with benign esophageal stenosis require multiple or even continuous balloon dilation treatments to achieve symptom relief. In this study, eighteen rabbits were used to establish an esophageal benign stenosis model and were divided into a control group (n = 6), a balloon group (n = 6) and a PTX-coated balloon group (n = 6) to evaluate the feasibility and effectiveness of paclitaxel (PTX)-coated balloons for the rabbit esophageal benign stenosis model. The weight and esophageal diameter were recorded every 2 weeks until 8 weeks post-surgery. Hematoxylin-eosin staining, Masson's trichrome staining and immunohistochemical staining were performed for pathological analysis. Four weeks post-operation, there was a significant difference in weight between the control group and the balloon group (p = 0.01) and between the control group and the PTX balloon group (p = 0.01). There was a significant difference in the esophageal diameter between the balloon group and the PTX balloon group at 8 weeks post-operation (p = 0.02). Four weeks post-operation, the degree of inflammatory cell infiltration in the PTX balloon group was significantly lower than that in the control group (p = 0.002) and balloon group (p = 0.001). The degree of collagen deposition in the PTX balloon group was significantly lower than that in the control group (p = 0.002) and balloon group (p = 0.03). Eight weeks post-operation, the percentage of cells positive for TGF-ß (p < 0.001), the degree of inflammatory cell infiltration (p = 0.02) and the degree of collagen deposition (p = 0.02) in the PTX balloon group were significantly lower than those in the balloon group. Therefore, PTX-coated balloons may alleviate the local inflammatory response and collagen deposition when used during dilation treatment of benign esophageal stenosis.


Assuntos
Estenose Esofágica , Paclitaxel , Animais , Humanos , Coelhos , Paclitaxel/farmacologia , Estenose Esofágica/terapia , Constrição Patológica , Colágeno , Catéteres , Resultado do Tratamento
16.
Drug Deliv Transl Res ; 14(3): 705-717, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37668861

RESUMO

As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm3, 0.37 ± 0.11 cm3, and 1.19 ± 0.16 cm3, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Neoplasias Gástricas , Animais , Coelhos , Oxaliplatina , Neoplasias Hepáticas/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Gástricas/tratamento farmacológico , Temperatura , Fator A de Crescimento do Endotélio Vascular
17.
ACS Nano ; 18(1): 245-263, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38117780

RESUMO

Poor clinical efficacy associated with postoperative hepatocellular carcinoma (HCC) often results from recurrence and metastasis. Hence, research has focused on establishing an effective multimodal therapy. However, complex combinations of active ingredients require multiple functions in therapeutic systems. Herein, a portable nanofiber patch composing germanium phosphorus (GeP) and anlotinib (AL) was designed to form a versatile platform for molecularly targeted photothermal-immune checkpoint blockade (ICB) trimodal combination therapy. The patches possess hydrophilic, satisfactory mechanical, and excellent photothermal conversion properties. Moreover, they achieve a penetrating and sustained drug release. The near-infrared light-assisted GeP-induced temperature increase regulates AL release, downregulating the expression of vascular-related factor receptors, triggering immunogenic cell death of tumor cells, and inducing dendritic cell maturation. Simultaneously, ICB therapy (programmed cell death ligand 1, PD-L1) was introduced to improve treatment outcomes. Notably, this trimodal combination therapy significantly inhibits vascular hypergrowth, enhances effector T-cell infiltration, and sensitizes the PD-L1 antibody response, boosting immunotherapy to suppress residual HCC recurrence and metastasis. Further validation of the genome sequencing results revealed cell pathways related primarily to regulatory immune effects. This study demonstrates the use of an effective and practical nanofiber patch to improve multimodal therapy of postoperative HCC, with high clinical translation value.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanofibras , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Antígeno B7-H1 , Nanofibras/uso terapêutico , Terapia Combinada , Imunoterapia/métodos , Microambiente Tumoral
19.
Anal Chem ; 95(50): 18564-18571, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38060825

RESUMO

The precision additive manufacturing and tessellated multitasking out of the structural DNA nanotechnology enable a configurable expression of densified electrochemiluminescent (ECL) complexes, which would streamline the bioconjugation while multiplying signals. Herein, a completely DNA-scaffold ECL "polyploid" was replicated out via the living course of rolling circle amplification. The amplicon carried the aptameric sequences of ZnPPIX/TSPP porphyrin as photoreactive centers that rallied at periodical intervals of the persistent extension into a close-packed nanoflower, ZnPDFI/II. Both microscopies and electrophoresis proved the robust nesting of guests at their deployed gene loci, while multispectral comparisons among cofactor substituents pinpointed the pivotal roles of singlet seclusion and Zn2+-chelation for the sake of intensive ECL irradiation. The adversity-resilient hydrogel texture made lipoidal filmogens as porphyrinic ECL prerequisites to be of no need at all, thus not only simplifying assay flows but also inspiring an in situ labeling plan. Upon bioprocessing optimization, an enriched probe ZnPDFIII was further derived that interpolated the binding motif related to calprotectin as validated by molecular docking and affinity titration. With it being a strongly indicative marker of inflammatory bowel disease (IBD), a competitive ECL aptasensing strategy was contrived, managing a signal-on and sensitive detection in mild conditions with a subnanogram-per-milliliter limit of detection by 2 orders of magnitude lower than the standard method as well as a comparable accuracy in clinical stool sample testing. Distinct from those conventional chemophysical rebuilding routes, this de novo biosynthetic fusion demonstrated a promising alternative toward ECL-source bioengineering, which may intrigue vibrant explorations of other ECL-shedding fabrics and, accordingly, a new bioanalytic mode downstream.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Limite de Detecção , Simulação de Acoplamento Molecular , Medições Luminescentes/métodos , DNA , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos
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