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1.
Int J Colorectal Dis ; 39(1): 108, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008124

RESUMO

BACKGROUND AND AIMS: Video-assisted anal fistula treatment (VAAFT) is an innovative surgical approach enabling the direct visualization of the fistula tract structure. This study aims to assess the efficacy of VAAFT in comparison with that of traditional surgical methods and explore potential risk factors contributing to fistula recurrence to provide new recommendations for surgical selection. MATERIALS AND METHODS: Information was collected from 100 patients with complex anal fistula (CAF) in our hospital who underwent surgical treatment from January 2021 to January 2023. We compared the baseline information and surgical outcomes of two groups, analyzed the risk factors for fistula recurrence by using logistic regression analysis, and conducted further exploration by using the body mass index. RESULTS: Equal numbers of patients underwent VAAFT and traditional surgeries, and no significant differences in baseline information were observed. Patients who received VAAFT experienced less intraoperative bleeding (15.5 (14.0-20.0) vs. 32.0 (25.0-36.0)), shorter hospital stays (2.0 (2.0-2.5) vs. 3.0 (3.0-3.5)), reduced postoperative pain and wound discharge, but longer operative times (43.3 ± 6.9 vs. 35.0 (31.5-40.0)) compared with patients who underwent traditional surgeries. No significant differences in recurrence rates were found three and six months after operation (the p-values were 0.790 and 0.806, respectively). However, the Wexner scores of the VAAFT group were significantly low in the first follow-up (0 (0-1.0) vs. 2.0 (1.0-2.0)). Postoperative recurrence of fistulas may be associated with obesity (p-value = 0.040), especially in patients undergoing traditional surgeries (p-value = 0.036). CONCLUSION: VAAFT offers advantages, such as less pain, less trauma, and faster recovery, compared with traditional surgical treatment. Obese patients with CAF are prone to recurrence, and we recommend that they undergo VAAFT treatment rather than traditional surgeries.


Assuntos
Obesidade , Fístula Retal , Recidiva , Cirurgia Vídeoassistida , Humanos , Fístula Retal/cirurgia , Fístula Retal/etiologia , Obesidade/complicações , Obesidade/cirurgia , Feminino , Masculino , Resultado do Tratamento , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Índice de Massa Corporal , Duração da Cirurgia , Tempo de Internação
2.
Int J Pharm ; : 124453, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39013531

RESUMO

Nanozymes, nanostructured materials emulating natural enzyme activities, exhibit potential in catalyzing reactive oxygen species (ROS) production for cancer treatment. By facilitating oxidative reactions, elevating ROS levels, and influencing the tumor microenvironment (TME), nanozymes foster the eradication of cancer cells. Noteworthy are their superior stability, ease of preservation, and cost-effectiveness compared to natural enzymes, rendering them invaluable for medical applications. This comprehensive review intricately explores the interplay between ROS and tumor therapy, with a focused examination of metal-based nanozyme strategies mitigating tumor hypoxia. It provides nuanced insights into diverse catalytic processes, mechanisms, and surface modifications of various metal nanozymes, shedding light on their role in intra-tumoral ROS generation and applications in antioxidant therapy. The review concludes by delineating specific potential prospects and challenges associated with the burgeoning use of metal nanozymes in future tumor therapies.

3.
World J Clin Oncol ; 15(6): 667-673, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38946830

RESUMO

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

4.
Medicine (Baltimore) ; 103(27): e38782, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968524

RESUMO

Lumbar spinal stenosis (LSS) can cause a range of cauda equina symptoms, including lower back and leg pain, numbness, and intermittent claudication. This disease affects approximately 103 million people worldwide, particularly the elderly, and can seriously compromise their health and well-being. Ligamentum flavum hypertrophy (LFH) is one of the main contributing factors to this disease. Surgical treatment is currently recommended for LSS caused by LFH. For patients who do not meet the criteria for surgery, symptom relief can be achieved by using oral nonsteroidal anti-inflammatory drugs (NSAIDs) and epidural steroid injections. Exercise therapy and needle knife can also help to reduce the effects of mechanical stress. However, the effectiveness of these methods varies, and targeting the delay in LF hypertrophy is challenging. Therefore, further research and development of new drugs is necessary to address this issue. Several new drugs, including cyclopamine and N-acetyl-l-cysteine, are currently undergoing testing and may serve as new treatments for LSS caused by LFH.


Assuntos
Hipertrofia , Ligamento Amarelo , Vértebras Lombares , Estenose Espinal , Humanos , Ligamento Amarelo/patologia , Estenose Espinal/terapia , Estenose Espinal/etiologia , Hipertrofia/etiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Terapia por Exercício/métodos , Tratamento Conservador/métodos
5.
Biochem Biophys Res Commun ; 723: 150173, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830299

RESUMO

The utilization of photothermal agents (PTAs) in photothermal therapy (PTT) is faced with challenges such as immune clearance and inadequate concentration, which consequently result in residual tumors and an increased risk of recurrence and metastasis. Conversely, excessive treatment can lead to heightened inflammation and inevitable harm to adjacent healthy tissues. To address these issues, we developed a nanosystem (M@PB) consisting of Prussian blue coated with tumor cell membrane for precise photothermal therapy (PTT) and subsequent reduction of inflammation. This system not only evades immune attack due to the homologous biological characteristics of the encapsulating cell membrane but also exhibits active targeting capabilities towards homologous tumors. Furthermore, it effectively reduces excessive phototoxicity by leveraging the distinctive photothermal and anti-inflammatory characteristics of PB nanoparticles. The resulting M@PB nanosystem demonstrates effective photothermal ablation under 808 nm laser irradiation while mitigating the inflammatory response through inhibiting of local production of inflammatory mediators. Our study provides valuable insights into achieving targeted PTT with high efficiency while minimizing post-treatment inflammatory responses.


Assuntos
Membrana Celular , Ferrocianetos , Inflamação , Nanopartículas , Terapia Fototérmica , Ferrocianetos/química , Terapia Fototérmica/métodos , Nanopartículas/química , Inflamação/terapia , Membrana Celular/metabolismo , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Neoplasias/terapia , Neoplasias/patologia
6.
Cell Oncol (Dordr) ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888850

RESUMO

PURPOSE: Uterine serous carcinoma (USC) is generally associated with poor prognosis due to a high recurrence rate and frequent treatment resistance; hence, there is a need for improved therapeutic strategies. Molecular analysis of USC identified several molecular markers, useful to improve current treatments or identify new druggable targets. PPP2R1A, encoding the Aα subunit of the tumor suppressive Ser/Thr phosphatase PP2A, is mutated in up to 40% of USCs. Here, we investigated the effect of the p.R183W PPP2R1A hotspot variant on treatment response to the nucleoside analogue clofarabine. METHODS AND RESULTS: USC cells stably expressing p.R183W Aα showed increased resistance to clofarabine treatment in vitro and, corroborated by decreased clofarabine-induced apoptosis, G1 phase arrest, DNA-damage (γH2AX) and activation of ATM and Chk1/2 kinases. Phenotypic rescue by pharmacologic PP2A inhibition or dicer-substrate siRNA (dsiRNA)-mediated B56δ subunit knockdown supported a gain-of-function mechanism of Aα p.R183W, promoting dephosphorylation and inactivation of deoxycytidine kinase (dCK), the cellular enzyme responsible for the conversion of clofarabine into its bioactive form. Therapeutic assessment of related nucleoside analogues (gemcitabine, cladribine) revealed similar effects, but in a cell line-dependent manner. Expression of two other PPP2R1A USC mutants (p.P179R or p.S256F) did not affect clofarabine response in our cell models, arguing for mutant-specific effects on treatment outcome as well. CONCLUSIONS: While our results call for PPP2R1A mutant and context-dependent effects upon clofarabine/nucleoside analogue monotherapy, combining clofarabine with a pharmacologic PP2A inhibitor proved synergistically in all tested conditions, highlighting a new generally applicable strategy to improve treatment outcome in USC.

7.
J Nanobiotechnology ; 22(1): 364, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915007

RESUMO

Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.


Assuntos
Imunoterapia , Nanomedicina , Terapia Fototérmica , Microambiente Tumoral , Animais , Terapia Fototérmica/métodos , Imunoterapia/métodos , Camundongos , Nanomedicina/métodos , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Neoplasias/terapia , Trifosfato de Adenosina/metabolismo , Adenosina/farmacologia , Adenosina/química , Camundongos Endogâmicos C57BL , Apirase/metabolismo , Feminino , Fototerapia/métodos
8.
Adv Mater ; 36(29): e2401640, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38710154

RESUMO

Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood-brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.


Assuntos
Glioblastoma , Nanopartículas , RNA Interferente Pequeno , Glioblastoma/terapia , Glioblastoma/patologia , Glioblastoma/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Humanos , Nanopartículas/química , Linhagem Celular Tumoral , Animais , Conformação Proteica , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Camundongos , Barreira Hematoencefálica/metabolismo , Materiais Biomiméticos/química
9.
Clin Chim Acta ; 560: 119734, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38777245

RESUMO

BACKGROUND: Ovarian cancer (OC) is a major global cause of death among gynecological cancers, with a high mortality rate. Early diagnosis, distinguishing between benign conditions and early malignant OC forms, is vital for successful treatment. This research investigates serum metabolites to find diagnostic biomarkers for early OC identification. METHODS: Metabolomic profiles derived from the serum of 60 patients with benign conditions and 60 patients with malignant OC were examined using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Comparative analysis revealed differential metabolites linked to OC, aiding biomarker identification for early-diagnosis of OC via machine learning features. The predictive ability of these biomarkers was evaluated against the traditional biomarker, cancer antigen 125 (CA125). RESULTS: 84 differential metabolites were identified, including 2-Thiothiazolidine-4-carboxylic acid (TTCA), Methionyl-Cysteine, and Citrulline that could serve as potential biomarkers to identify benign conditions and malignant OC. In the diagnosis of early-stage OC, the area under the curve (AUC) for Citrulline was 0.847 (95 % Confidence Interval (CI): 0.719-0.974), compared to 0.770 (95 % CI: 0.596-0.944) for TTCA, and 0.754 for Methionine-Cysteine (95 % CI: 0.589-0.919). These metabolites demonstrate a superior diagnostic capability relative to CA125, which has an AUC of 0.689 (95 % CI: 0.448-0.931). Among these biomarkers, Citrulline stands out as the most promising. Additionally, in the diagnosis of benign conditions and malignant OC, using logistic regression to combine potential biomarkers with CA125 has an AUC of 0.987 (95 % CI: 0.9708-1) has been proven to be more effective than relying solely on the traditional biomarker CA125 with an AUC of 0.933 (95 % CI: 0.870-0.996). Furthermore, among all the differential metabolites, lipid metabolites dominate, significantly impacting glycerophospholipid metabolism pathway. CONCLUSION: The discovered serum metabolite biomarkers demonstrate excellent diagnostic performance for distinguishing between benign conditions and malignant OC and for early diagnosis of malignant OC.


Assuntos
Biomarcadores Tumorais , Detecção Precoce de Câncer , Metabolômica , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/metabolismo , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Adulto , Espectrometria de Massas em Tandem , Idoso , Cromatografia Líquida de Alta Pressão
10.
Adv Healthc Mater ; : e2304421, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780250

RESUMO

Developing small-molecule photothermal agents (PTAs) with good near-infrared-II (NIR-II) response for deeper tissue penetration and minimizing damage to healthy tissues has attracted much attention in photothermal therapy (PTT). However, concentrating ultra-long excitation wavelengths and high photothermal conversion efficiencies (PCEs) into a single organic small molecule is still challenging due to the lack of suitable molecular structures. Here, six polymethine cyanine molecules based on the structure of indocyanine green are synthesized by increasing the conjugated structure of the two-terminal indole salts and the number of rigid methine units, and incorporating longer alkyl side chains into the indole salts. Ultimately, IC-1224 is obtained with an absorption wavelength of more than 1200 nm, which has a high PCE up to 83.2% in the NIR-II window and exhibits excellent PTT tumor ablation performance. This provides a high-performance NIR-II-responsive PTA, and offers further possibilities for the application of PTT in biomedical fields.

11.
Adv Sci (Weinh) ; 11(26): e2402759, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704681

RESUMO

Soft on-skin electrodes play an important role in wearable technologies, requiring attributes such as wearing comfort, high conductivity, and gas permeability. However, conventional fabrication methods often compromise simplicity, cost-effectiveness, or mechanical resilience. In this study, a mechanically robust and gas-permeable on-skin electrode is presented that incorporates Flash Graphene (FG) integrated with a bioinspired armor design. FG, synthesized through Flash Joule Heating process, offers a small-sized and turbostratic arrangement that is ideal for the assembly of a conductive network with nanopore structures. Screen-printing is used to embed the FG assembly into the framework of polypropylene melt-blown nonwoven fabrics (PPMF), forming a soft on-skin electrode with low sheet resistance (125.2 ± 4.7 Ω/□) and high gas permeability (≈10.08 mg cm⁻2 h⁻¹). The "armor" framework ensures enduring mechanical stability through adhesion, washability, and 10,000 cycles of mechanical contact friction tests. Demonstrating capabilities in electrocardiogram (ECG) and electromyogram (EMG) monitoring, along with serving as a self-powered triboelectric sensor, the FG/PPMF electrode holds promise for scalable, high-performance flexible sensing applications, thereby enriching the landscape of integrated wearable technologies.


Assuntos
Eletrodos , Grafite , Dispositivos Eletrônicos Vestíveis , Grafite/química , Humanos , Desenho de Equipamento/métodos , Permeabilidade , Nanoporos , Eletrocardiografia/métodos , Gases
12.
Biomater Res ; 28: 0028, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715912

RESUMO

The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganese-based nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn2+ accomplishes multiple objectives. It generates toxic hydroxyl radicals (•OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O2) from hydrogen peroxide (H2O2), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS-STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.

13.
ACS Appl Mater Interfaces ; 16(22): 28011-28028, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38783516

RESUMO

In vivo real-time qualitative and quantitative analysis is essential for the diagnosis and treatment of diseases such as tumors. Near-infrared-II (NIR-II, 1000-1700 nm) bioimaging is an emerging visualization modality based on fluorescent materials. The advantages of NIR-II region fluorescent materials in terms of reduced photon scattering and low tissue autofluorescence enable NIR-II bioimaging with high resolution and increasing depth of tissue penetration, and thus have great potential for in vivo qualitative and quantitative analysis. In this review, we first summarize recent advances in NIR-II imaging, including fluorescent probe selection, quantitative analysis strategies, and imaging. Then, we describe in detail representative applications to illustrate how NIR-II fluorescence imaging has become an important tool for in vivo quantitative analysis. Finally, we describe the future possibilities and challenges of NIR-II fluorescence imaging.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Corantes Fluorescentes/química , Imagem Óptica/métodos , Humanos , Animais , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Neoplasias/diagnóstico por imagem , Raios Infravermelhos
14.
Oncol Lett ; 28(1): 294, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38737980

RESUMO

Flurbiprofen axetil or dezocine monotherapy has been applied for analgesia of postoperative non-small cell lung cancer (NSCLC); however, their combination is rarely investigated. Consequently, the present study aimed to explore the effect of flurbiprofen axetil plus dezocine on postoperative pain, surgical outcomes and its safety profile in patients with NSCLC. A total of 150 patients with resectable NSCLC were enrolled and randomized into three groups: i) The flurbiprofen axetil plus dezocine group (n=50), ii) the flurbiprofen axetil group (n=51) and iii) the dezocine group (n=49). A total of 50 mg flurbiprofen axetil, 5 mg of dezocine or their combination were administered intravenously 3 h prior to surgery and subsequently every 12 h until day 3 (D3) following surgery. The postoperative pain was lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil group at 6 h (P=0.008), 12 h (P=0.003), day 1 (D1) (P=0.013), day 2 (D2) (P=0.036) and D3 (P=0.010); in addition, it was lower in the flurbiprofen axetil plus dezocine group compared with that of the dezocine group at 6 h (P=0.010), 12 h (P=0.012) and D1 (P=0.020). Patient-controlled analgesia consumption was also lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil (P=0.010) and dezocine (P=0.002) groups. Furthermore, the length of hospital stay was lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil (P=0.008) and dezocine (P=0.048) groups, while other surgical outcomes and adverse events were similar among these three groups. Moreover, the expression of tumor necrosis factor-α was lower in the flurbiprofen axetil plus dezocine group compared with that of the dezocine group at 12 h (P<0.001), D1 (P<0.001) and D3 (P=0.033). The data indicated that flurbiprofen axetil and dezocine combination was superior to monotherapy for postoperative analgesia in patients with resectable NSCLC.

15.
Ther Drug Monit ; 46(3): 291-308, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648666

RESUMO

BACKGROUND: Infliximab, an anti-tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research. METHODS: The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement. RESULTS: Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record-integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration. CONCLUSIONS: Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory.


Assuntos
Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais , Infliximab , Humanos , Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Infliximab/farmacocinética
16.
Int Immunopharmacol ; 132: 111923, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38565041

RESUMO

In this study, we aimed to evaluate the protective effect of geniposide (GEN) on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Firstly, visual changes of psoriatic skin lesions were observed and the severity was recorded using psoriasis area and severity index (PASI) score. Histological changes were assessed by HE staining for epidermal thickness and Masson's staining for collagen fibers. Then, photographs of microvascular inside the skin were taken for macroscopic observation, and microscopic changes associated with angiogenesis were evaluated. Furthermore, expression of angiogenic factors were analyzed by ELISA, immunohistochemistry and immunofluorescence, separately. Lastly, the expression of VEGFR signaling-related proteins was detected by WB. Compared with control, IMQ drove a significant increment of epidermal thicknesses with higher PASI scores and more dermal collagen deposition. IMQ treatment led to abnormal keratinocyte proliferation, increased microvascular inside skin, growing production of angiogenesis-related factors, up-regulated expression of VEGFR1 and VEGFR2, and enhanced phosphorylation of p38. However, GEN significantly ameliorated the psoriatic skin lesions, the epidermal thickness, the formation of collagen fibers, and abnormal keratinocyte proliferation. Importantly, GEN inhibited angiogenesis, the production of angiogenic factors (VEGF-A, Ang-2, TNF-α, and IL-17A), and the proliferation of vascular endothelial cells. Simultaneously, GEN curbed the expression of VEGFR1, VEGFR2, p38, and P-p38 proteins involved in VEGFR signaling. Of note, the suppressive effect of GEN was reversed in the HUVECs with over-expressed VEGFR1 or VEGFR2 related to the cells without transfection. These findings suggest that VEGFR1 and VEGFR2 participate in the anti-angiogenesis of GEN in IMQ-induced psoriasis-like skin lesions in mice.


Assuntos
Imiquimode , Iridoides , Neovascularização Patológica , Psoríase , Pele , Animais , Masculino , Camundongos , Angiogênese , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Imiquimode/toxicidade , Iridoides/farmacologia , Iridoides/uso terapêutico , Queratinócitos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Psoríase/patologia , Pele/patologia , Pele/efeitos dos fármacos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
Biomaterials ; 308: 122570, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38636133

RESUMO

Metallic biomaterials activate tumor ferroptosis by increasing oxidative stress, but their efficacy is severely limited in tumor microenvironment. Although interferon gamma (IFN-γ) can promote tumor ferroptosis sensitivity by inhibiting the antioxidant system and promoting lipid accumulation, this effect limited by the lack of IFN-γ accumulation in tumors. Herein, we report a near-infrared (NIR)-responsive HCuS nanocomposite (HCuS-PE@TSL-tlyp-1) that can stimulate immunogenic cell death (ICD)-mediated IFN-γ secretion through exogenous oxidative stress, thereby achieving cascaded ferrotherapy by mutually reinforcing ferroptosis and systemic immunity. Upon laser irradiation, the dissolution of the thermal coating, and the introduction of Cu ions and piperazine-erastin (PE) simultaneously induce oxidative stress by reactive oxygen species (ROS)/lipid peroxide (LPO) accumulation and deplete cystine-glutamate transporter (xCT)/GSH. The onset of oxidative stress-mediated ferroptosis is thus achieved, and ICD is triggered, significantly promoting cytotoxic T-cell (CTL) infiltration for IFN-γ secretion. Furthermore, IFN-γ induces immunogenic tumor ferroptosis by inhibiting xCT-antioxidant pathways and enhancing the ACSL4-fatty acid recruitment pathway, which further promotes sensitivity to ferroptosis in cells. These HCuS nanocomposites combined with aPD-L1 effectively in inhibiting tumor metastasis and recurrence. Importantly, these cascade ferrotherapy results broadens the application of HCuS biomaterials.


Assuntos
Cobre , Ferroptose , Interferon gama , Lipossomos , Ferroptose/efeitos dos fármacos , Animais , Cobre/química , Cobre/farmacologia , Interferon gama/metabolismo , Camundongos , Lipossomos/química , Nanocompostos/química , Linhagem Celular Tumoral , Morte Celular Imunogênica/efeitos dos fármacos , Raios Infravermelhos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo
18.
Biomed Pharmacother ; 174: 116486, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520865

RESUMO

Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.


Assuntos
Lipossomos , Células-Tronco Neoplásicas , Fármacos Fotossensibilizantes , Terapia Fototérmica , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Humanos , Terapia Fototérmica/métodos , Animais , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Indóis/farmacologia , Indóis/química , Nanopartículas/química , Camundongos Nus , Terapia Combinada , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Nanocompostos/química
19.
Quant Imaging Med Surg ; 14(3): 2267-2279, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38545039

RESUMO

Background: Diabetes mellitus can occur after acute pancreatitis (AP), but the accurate quantitative methods to predict post-acute pancreatitis diabetes mellitus (PPDM-A) are lacking. This retrospective study aimed to establish a radiomics model based on contrast-enhanced computed tomography (CECT) for predicting PPDM-A. Methods: A total of 374 patients with first-episode AP were retrospectively enrolled from two tertiary referral centers. There were 224 patients in the training cohort, 56 in the internal validation cohort, and 94 in the external validation cohort, and there were 86, 22, and 27 patients with PPDM-A in these cohorts, respectively. The clinical characteristics were collected from the hospital information system. A total of 2,398 radiomics features, including shape-based features, first-order histogram features, high order textural features, and transformed features, were extracted from the arterial- and venous-phase CECT images. Intraclass correlation coefficients were used to assess the intraobserver reliability and interobserver agreement. Random forest-based recursive feature elimination, collinearity analysis, and least absolute shrinkage and selection operator (LASSO) were used for selecting the final features. Three classification methods [eXtreme Gradient Boosting (XGBoost), Adaptive Boosting, and Decision Tree] were used to build three models and performances of the three models were compared. Each of the three classification methods were used to establish the clinical model, radiomics model, and combined model for predicting PPDM-A, resulting in a total of nine classifiers. The predictive performances of the models were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. Results: Eleven radiomics features were selected after a reproducibility test and dimensionality reduction. Among the three classification methods, the XGBoost classifier showed better and more consistent performances. The AUC of the XGBoost's radiomics model to predict PPDM-A in the training, internal, and external cohorts was good (0.964, 0.901, and 0.857, respectively). The AUC of the XGBoost's combined model to predict PPDM-A in the training, internal, and external cohorts was good (0.980, 0.901, and 0.882, respectively). The AUC of the XGBoost's clinical model to predict PPDM-A in the training, internal, and external cohorts did not perform well (0.685, 0.733, and 0.619, respectively). In the external validation cohort, the AUC of the XGBoost's radiomics model was significantly higher than that of the clinical model (0.857 vs. 0.619, P<0.001), but there was no significant difference between the combined and radiomics models (0.882 vs. 0.857, P=0.317). Conclusions: The radiomics model based on CECT performs well and can be used as an early quantitative method to predict the occurrence of PPDM-A.

20.
Front Cardiovasc Med ; 11: 1335552, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545347

RESUMO

Background: This study aims to analyze the risk factors associated with prolonged mechanical ventilation (PMV) in patients following surgical treatment for acute type A aortic dissection (ATAAD). The objectives include constructing a predictive model for risk assessment and validating its predictive efficacy. Methods: A total of 452 patients diagnosed with ATAAD and undergoing surgical procedures at a tertiary hospital in Nanjing between January 2021 and April 2023 were selected using a convenience sampling method. Patients were categorized into two groups: PMV group (n = 132) and non-PMV group (n = 320) based on the occurrence of prolonged mechanical ventilation (PMV), and their clinical data were compared. The data were randomly divided into a modeling set and a validation set in a 7:3 ratio. Risk factors for PMV were identified in the modeling group using logistic regression analysis. A risk prediction model was constructed using R 4.1.3 software, visualized via a column chart. Receiver Operating Characteristic (ROC) curves were generated using the validation set to assess model differentiation. Calibration curves were plotted to evaluate accuracy and consistency, and Decision Curve Analysis (DCA) was applied to evaluate clinical utility. Results: The logistic regression analysis identified age, body mass index, preoperative white blood cell count, preoperative creatinine, preoperative cerebral hypoperfusion, and cardiopulmonary bypass time as significant risk factors for postoperative PMV in patients with ATAAD. The area under the curve (AUC) for the validation set ROC curve was 0.856, 95% confidence interval (0.805-0.907), indicating good discrimination. Calibration curves revealed strong alignment with the ideal curve, and the Hosmer-Lemeshow goodness-of-fit test indicated a well-fitted model (P = 0.892). The DCA curve demonstrated a high net benefit value, highlighting the model's strong clinical utility. Conclusions: The risk prediction model developed in this study for PMV in patients undergoing surgery for ATAAD exhibits robust predictive performance. It provides valuable insights for healthcare practitioners in predicting the likelihood of PMV and devising timely and personalized intervention strategies.

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