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1.
RSC Adv ; 13(3): 2190-2201, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36712617

RESUMO

Developing new biomaterials is an active research area owing to their applications in regenerative medicine, tissue engineering and drug delivery. Elastin-like polypeptides (ELPs) are good candidates for these applications because they are biosourced, biocompatible and biodegradable. With the aim of developing ELP-based micelles for drug delivery applications we have synthesized 15 acyl-ELP compounds by conjugating myristic, palmitic, stearic, oleic or linoleic acid to the N-terminus of three ELPs differing in molar mass. The ELP-fatty acid conjugates have interesting solution behavior. They form micelles at low temperatures and aggregate above the cloud point temperature (Tcp). The critical micelle concentration depends on the fatty acid nature while the micelle size is mainly determined by the ELP block length. We were able to show that ELPs were better hydrated in the micelles than in their individual state in solution. The micelles are stable in phosphate-buffered saline at temperatures below the Tcp, which can vary between 20 °C and 38 °C depending on the length or hydrophilicity of the ELP. Acyl-ELP micelles were loaded with the small hydrophobic molecule Nile red. The encapsulation efficiency and release kinetics showed that the best loading conditions were achieved with the largest ELP conjugated to stearic acid.

2.
Adv Healthc Mater ; : e2202695, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622285

RESUMO

Methionine metabolism has a significant impact on T cells' survival and activation even in comparison to arginine, a well-documented amino acid in metabolic therapy. However, hydrophilic methionine is hardly delivered into TME due to difficult loading and rapid diffusion. Herein, the labeling assembly of methionine into nanoparticle is developed to overcome high hydrophilicity for mild-heat mediated immunometabolic therapy. The strategy is to firstly label methionine with protocatechualdehyde (as the tag) via reversible Schiff-base bond, and then drive nano-assembly of methionine (MPC@Fe) mediated by iron ions. In this fashion, a loading efficiency of 40% and assembly induced photo-thermal characteristics could be achieved. MPC@Fe can accumulate persistently in tumor up to 36 h due to tumor-selective aggregation in acidic TME. A mild heat of 43°C on tumor by light irradiation stimulated the immunogenic cell death and effectively generated CD8+ T cells. Notably, MPC@Fe assisted by mild heat promoted 4.2-fold of tumor-infiltrating INF-γ+ CD8+ T cells, leading to an inhibition ratio of 27.3-fold versus the free methionine. Such labeling assembly provides a promising methionine delivery platform to realize mild heat mediated immunometabolic therapy, and is potentially extensible to other amino acids. This article is protected by copyright. All rights reserved.

3.
Cancer Res ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622331

RESUMO

Tumor-associated macrophages (TAMs) play a crucial role in immunosuppression. However, how TAMs are transformed into immunosuppressive phenotypes and influence the tumor microenvironment (TME) is not fully understood. Here, we utilized single-cell RNA sequencing and whole-exome sequencing data of glioblastoma (GBM) tissues and identified a subset of TAMs dually expressing macrophage and tumor signatures, which were termed double-positive TAMs. Double-positive TAMs tended to be bone marrow-derived macrophages (BMDMs) and were characterized by immunosuppressive phenotypes. Phagocytosis of glioma cells by BMDMs in vitro generated double-positive TAMs with similar immunosuppressive phenotypes to double-positive TAMs in the GBM TME of patients. The double-positive TAMs were transformed into M2-like macrophages and drove immunosuppression by expressing immune checkpoint proteins CD276, PD-L1, and PD-L2 and suppressing the proliferation of activated T cells. Together, glioma cell phagocytosis by BMDMs in the TME leads to the formation of double-positive TAMs with enhanced immunosuppressive phenotypes, shedding light on the processes driving TAM-mediated immunosuppression in GBM.

4.
Bioresour Technol ; 370: 128557, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36587773

RESUMO

Understanding the relationship between dynamic microbial networks and functional stability is critical for the stable operation of anammox systems. Here, by operating an anammox reactor under constant condition over 250 days, it was found that the relative abundance of Planctomycetota gradually decreased while Chloroflexi and Proteobacteria increased, with stochasticity predominating the bacterial assembly as the reactor operation. Network analysis revealed a successional dynamic pattern of microbial interaction despite stable performance. The variation of subnetworks indicated Chloroflexi and Proteobacteria alternately played important role in anammox microbial network, and the negative relationship between anammox bacteria and heterotrophs could achieve a balance to keep functional stability under long-term operation. Furthermore, the identified keystone species mainly belonged to heterotrophs that were critical in maintaining network structure and system function. The results of this study revealed clear changing patterns of microbial community and network succession, which could provide valuable reference for other stably operated bioreactors.


Assuntos
Oxidação Anaeróbia da Amônia , Microbiota , Nitrogênio , Bactérias , Proteobactérias , Reatores Biológicos/microbiologia , Oxirredução
5.
Plant Physiol Biochem ; 195: 89-100, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36621305

RESUMO

Trihelix transcription factors consist of five subfamilies, including GT-1, GT-2, SH4, GTγ, and SIP1, which play important roles in the responses to biotic and abiotic stresses, however, seldom is known about the role of the SIP1 genes in apples. In this study, 12 MdSIP1 genes were first identified in apples by genome-wide analysis, and contained conserved MYB/SANT-like domains. Expression patterns analyses showed that the MdSIP1 genes had different tissue expression patterns, and different transcription levels in response to abiotic stresses, indicating that MdSIP1s may play multiple roles under various abiotic stresses. Among them, the MdSIP1-2 gene was cloned and ectopic transformed into Arabidopsis, and its biology function was identified. The subcellular localization showed that MdSIP1-2 protein was specifically localized in the nucleus, and that overexpression of MdSIP1-2 promoted the development of lateral roots, increased abscisic acid (ABA) sensitivity, and improved salt and drought tolerance. These findings suggested that MdSIP1-2 plays an important role in root development, ABA synthesis, and salt and drought stress tolerance. In conclusion, these results lay a solid foundation for determining the role of MdSIP1 in the growth and development and abiotic stress tolerance of apples.


Assuntos
Arabidopsis , Malus , Malus/genética , Malus/metabolismo , Arabidopsis/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Genoma de Planta/genética , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Secas , Plantas Geneticamente Modificadas/genética
6.
J Chem Inf Model ; 63(2): 493-506, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36632804

RESUMO

Both reversible noncovalent inhibitors and irreversible covalent inhibitors targeting tyrosine kinases have their disadvantages. The reversible covalent inhibitors with electrophilic group cyanoacrylamide as warheads reacting with cysteine residues could solve the dilemmas. However, there are still several unresolved issues regarding the electrophilic groups. In this manuscript, a series of EGFR inhibitors with double electron-withdrawing substituents introduced into the Cα position on the olefin bond were designed and synthesized. The binding structures and characteristics of inhibitors with the kinase in both the first noncovalent binding phase and the second covalent binding step were explored and combined with molecular docking and molecular dynamics simulations. Then, the reverse ß-elimination reactions of the thiol-Michael adducts were investigated by applying density functional theory calculations. In addition, the effects of different electrophilic substituents of Cα on the binding between the inhibitors and kinase were elucidated. The results suggested that the electrophilicity and size of the electron-withdrawing groups play an important role in the specific interactions during the reaction. The compounds with the electron-withdrawing groups that had medium electrostatic and steric complementarity to the kinase active site could cooperatively stabilize the complexes and showed relatively good potent activities in the kinase assay experiment. The mechanical and structural information in this study could enhance our understanding of the functioning of the electron-withdrawing groups in the covalent inhibitors. The results might help to design efficient cysteine targeting inhibitors in the future.


Assuntos
Cisteína , Compostos de Sulfidrila , Cisteína/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases/química
7.
Colloids Surf B Biointerfaces ; 222: 113134, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36630772

RESUMO

The discovery of P-Glycoprotein (P-gp) inhibitors to block chemotherapy drugs efflux is considered an attractive treatment strategy for overcoming cancer multidrug resistance (MDR). Cell membrane biomimetic platform has emerged as a promising candidate method for screening small molecule P-gp inhibitors from natural products. However, randomly oriented cell membrane coating does not guarantee the inward-opening conformation of P-gp, limiting the precise screening of P-gp inhibitors. Herein, inside-out orientation extracellular vesicles camouflaged magnetic nanoparticles (IOVMNPs) were prepared to discover P-gp inhibitors with low toxicity and high efficiency from natural products. The orientation of extracellular vesicles on the surface of IOVMNPs was rigorously confirmed by immunogold electron microscopy and sialic acid quantification assay. Finally, two potential P-gp inhibitors, honokiol and magnolol, were captured by obtained IOVMNPs. The effect of MDR reversal in combination with chemotherapy drugs was further verified by pharmacological activity experiments. The inside-out orientation extracellular vesicles encapsulation strategy provides an effective tool for the discovery of novel P-gp inhibitors from nature products, thus further extending the application field of orientation assembly cell membrane biomimetic magnetic nanoparticles. This inside-out extracellular vesicles coating also proposes a new concept for the assembly of cell membrane biomimetic platform.

9.
J Colloid Interface Sci ; 637: 477-488, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36716671

RESUMO

Although most solar steam generation devices are effective in desalinating seawater and purifying wastewaters with heavy metal ions, they are ineffective in degrading organic pollutants from wastewaters. Herein, we design novel solar-driven water purification devices by decoration of three-dimensional pinecones with MoS2 nanoflowers via a one-step hydrothermal synthesis for generating clean water. The vertically arrayed channels in the central rachis and the unique helically arranged scales of the hydrothermal pinecone can not only transfer bulk water upward to the evaporation surface, but also absorb more solar light from different incident angles for solar-thermal evaporation and photodegradation of wastewaters under omnidirectional irradiations. The decorated MoS2 nanoflowers can not only enhance the solar-thermal energy conversion efficiency, but also decompose organic pollutants in the bulk water by their photocatalytic degradation effects. The resultant hydrothermal pinecone with in situ decorated MoS2 (HPM) evaporator exhibits a high evaporation rate of 1.85 kg m-2 h-1 under 1-sun irradiation with a high energy efficiency of 96 %. During the solar-driven water purification processes, the powdery HPM can also photodegrade organic pollutants of methylene blue and rhodamine B with high removal efficiencies of 96 % and 95 %, respectively. For practical demonstration, by floating in the methylene blue solution under 1-sun irradiation, the bulky HPM can generate clean water by simultaneous solar-thermal evaporation and photocatalytic degradation. The integration of solar steam generation and photocatalytic degradation mechanisms makes the HPM evaporator highly promising for practical high-yield purification of wastewaters.

10.
Transl Psychiatry ; 13(1): 5, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624089

RESUMO

Mood disorders are associated with elevated inflammation, and the reduction of symptoms after multiple treatments is often accompanied by pro-inflammation restoration. A variety of neuromodulation techniques that regulate regional brain activities have been used to treat refractory mood disorders. However, their efficacy varies from person to person and lack reliable indicator. This review summarizes clinical and animal studies on inflammation in neural circuits related to anxiety and depression and the evidence that neuromodulation therapies regulate neuroinflammation in the treatment of neurological diseases. Neuromodulation therapies, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), electroconvulsive therapy (ECT), photobiomodulation (PBM), transcranial ultrasound stimulation (TUS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS), all have been reported to attenuate neuroinflammation and reduce the release of pro-inflammatory factors, which may be one of the reasons for mood improvement. This review provides a better understanding of the effective mechanism of neuromodulation therapies and indicates that inflammatory biomarkers may serve as a reference for the assessment of pathological conditions and treatment options in anxiety and depression.


Assuntos
Estimulação Encefálica Profunda , Eletroconvulsoterapia , Animais , Estimulação Encefálica Profunda/métodos , Depressão/terapia , Doenças Neuroinflamatórias , Eletroconvulsoterapia/métodos , Estimulação Magnética Transcraniana/métodos , Ansiedade/terapia
11.
FASEB J ; 37(2): e22758, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36607288

RESUMO

Stress in the endoplasmic reticulum (ER) may perturb proteostasis and activates the unfolded protein response (UPR). UPR activation is frequently observed in cancer cells and is believed to fuel cancer progression. Here, we report that one of the three UPR sensors, ATF6α, was associated with prostate cancer (PCa) development, while both genetic and pharmacological inhibition of ATF6α impaired the survival of castration-resistance PCa (CRPC) cells. Transcriptomic analyses identified the molecular pathways deregulated upon ATF6α depletion, and also discovered considerable disparity in global gene expression between ATF6α knockdown and Ceapin-A7 treatment. In addition, combined analyses of human CRPC bulk RNA-seq and single-cell RNA-seq (scRNA-seq) public datasets confirmed that CRPC tumors with higher ATF6α activity displayed higher androgen receptor (AR) activity, proliferative and neuroendocrine (NE) like phenotypes, as well as immunosuppressive features. Lastly, we identified a 14-gene set as ATF6α NE gene signature with encouraging prognostic power. In conclusion, our results indicate that ATF6α is correlated with PCa progression and is functionally relevant to CRPC cell survival. Both specificity and efficacy of ATF6α inhibitors require further refinement and evaluation.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Resposta a Proteínas não Dobradas , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Linhagem Celular Tumoral , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
12.
Microb Biotechnol ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36636832

RESUMO

A double-stranded RNA (dsRNA) phage phiYY is able to kill a pyomelanin-producing Pseudomonas aeruginosa strain, which was isolated from a 40-year-old man with interstitial lung disease (ILD) and chronic lung infection. Phage therapy was used as a last resort for this patient. The three-course nebulized phiYY treatment was used to reduce the bacterial burden and clinical symptoms of the patient. Recurrences of P. aeruginosa infections were observed 1-3 days post phage therapy. The recurrent isolates exhibited distinct antibiotic-susceptibility profiles compared with the original strain yet were still susceptible to phiYY. This assay represents the application of dsRNA phage in the treatment of chronic lung infection, albeit the safety and efficacy of the dsRNA phage require further assessment.

13.
Talanta ; 256: 124256, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36641996

RESUMO

A crucial issue in analytical science and physiology is the detection of histamine with high sensitivity, specificity and credibility, which served as an important neurotransmitter in biofluids. Despite the high sensitivity of surface-enhanced Raman spectroscopy (SERS) at the level of single molecule, there are still challenges in providing high sensitivity for histamine with a small cross section. For the selective detection of histamine using SERS, a highly sensitive sandwich structure substrate combining Fe3O4 and an Ag-based SERS nanotag was developed. The Fe3O4@SiO2-COOH served as a capture component for enriching histamine. Upon functionalized Ag nanoparticles with glycine (Gly) and (3-Aminopheyonyl) boronic acid (APBA), they were then used to connect with histamine and serve as a SERS nanotag, respectively. A linear relationship between the Raman intensity and the histamine concentration was observed over the range 10-4-10-8 M with a limit of detection of 7.24 × 10-9 M. This methodology also exhibited good selectivity in the presence of other neurotransmitters. With our new approach, histamine can be detected sensitively and reliably in fish samples, which indicates the potential prospect of an effective method for analyzing histamine in complex specimens.

14.
Microbiol Spectr ; : e0261622, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625668

RESUMO

Generation of hybrid MDR plasmids accelerated the evolution and transmission of resistance genes. In this study, we characterized a blaKPC-2- and blaIMP-4-coharboring conjugative hybrid plasmid constituted of an IncHI5 plasmid-like region, an IncFII(Yp)/IncFIA plasmid-like region, and a KPN1344 chromosome-like region from a clinical ST852-KL18 Klebsiella quasipneumoniae strain. The blaIMP-4 gene was captured by a novel integron In1965, and the blaKPC-2 gene was located on a new non-Tn4401 group I NTEKPC element. Both blaKPC-2- and blaIMP-4-containing genetic architectures were distinguished from classical structures, highlighting the constant evolution of these genetic elements. IMPORTANCE The emergence of carbapenem-resistant Enterobacterales (CRE) that coexpress serine- and metallo-carbapenemases is a severe threat to the efficacy of ceftazidime-avibactam (CZA), which has been proven to be extremely effective against KPC-producing Enterobacterales strains. Our study described the cooccurrence of KPC-2, a serine ß-lactamase, and IMP-4, a metallo-ß-lactamase (MBL), on a conjugative hybrid plasmid from a clinical carbapenem-resistant K. quasipneumoniae strain, and it revealed an alternative route for IncHI5 plasmid to evolve by recombining with other plasmids to form a hybrid plasmid. Moreover, this hybrid plasmid can be transferred into other Klebsiella species and stably persist during passage. The propagation of two important carbapenemase genes with a new genetic background using well-evolved plasmids in the clinical setting promotes the emergence of superbugs that require careful monitoring.

15.
Int Immunopharmacol ; 114: 109595, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36700774

RESUMO

Methotrexate (MTX) is used to treat rheumatoid arthritis, acute leukemia, and psoriasis. MTX can cause certain side effects, such as myelosuppression, while the exact mechanism of myelosuppression caused by MTX is unknown. Notch signaling pathway has been considered to be essential to regulate hematopoietic stem cell (HSC) regeneration and homeostasis, thus contributing to bone marrow hematopoiesis. However, whether MTX affects Notch signaling remains unexplored. Here, our study provides evidence that MTX strongly suppresses the Notch signaling pathway. We found that MTX inhibited the interaction between Nedd4 with Numb, thus restricting K48-linked polyubiquitination of Numb and stabilizing Numb proteins. This in turn inhibited the Notch signaling pathway by reducing Notch1 protein levels. Interestingly, we found that a monomeric drug, Triptolide, is capable of alleviating the inhibitory effect of MTX on Notch signaling pathway. This study promotes our understanding of MTX-mediated regulation of Notch signaling and could provide ideas to alleviate MTX-induced myelosuppression.


Assuntos
Metotrexato , Receptores Notch , Proteínas de Membrana/metabolismo , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Receptor Notch1 , Receptores Notch/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
16.
J Mater Chem B ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36650960

RESUMO

Apoptosis-based treatment plays an important role in regulating the death of tumor cells (e.g., chemotherapy, radiotherapy, and immunotherapy). Nevertheless, cancer cells can escape surveillance from apoptosis-associated signaling by bypassing other biological pathways and thus result in considerable resistance to therapies. Significantly, ferroptosis, a newly identified type of regulated cell death that is characterized by iron-dependent and lipid peroxidation accumulation, has aroused great research interest in cancer therapy. Increasing approaches have been developed to induce ferroptosis of tumor cells, including using clinically approved drugs, experimentally used compounds, and nanomedicine formulations. More importantly, the emerging nanomedicine-based strategy has made great advances in tumor treatment because of the promising targeting efficacy and enhanced therapeutic effects. In this review, we mainly overview state-of-the-art research on nanomedicine-mediated ferroptosis targeting strategies for synergistic cancer therapies, such as immunotherapy, chemotherapy, radiotherapy, and photothermal therapy. The potential targeting mechanism of nanomedicine for ferroptosis induction was also included. Finally, the future development of nanomedicine in the field of ferroptosis-based cell death in tumor treatment will be envisioned, aiming to provide new insight for tumor treatment in the clinic.

17.
Theranostics ; 13(1): 106-124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593948

RESUMO

Rationale: The accumulation and clearance of amyloid-ß (Aß) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). The (re)discovery of meningeal lymphatic vessels in recent years has focused attention on the lymphatic clearance of Aß and has become a promising therapeutic target for such diseases. However, there is a lack of small molecular compounds that could clearly regulate meningeal lymphatic drainage to remove Aß from the brain. Methods: We investigated the effect of borneol on meningeal lymphatic clearance of macromolecules with different molecular weights (including Aß) in the brain. To further investigate the mechanism of borneol regulating meningeal lymphatic drainage, immunofluorescence staining, western blotting, ELISA, RT-qPCR, and Nitric Oxide assay kits were used. The cognitive function of AD mice after borneol treatment was evaluated using two behavioral tests: open field (OF) and Morris water maze (MWM). Results: This study discovered that borneol could accelerate the lymphatic clearance of Aß from the brain by enhancing meningeal lymphatic drainage. Preliminary mechanism analysis revealed that borneol could improve the permeability and inner diameter of lymphatic vessels, allowing macromolecules to drain into the cervical lymph nodes (CLNS) and then be transported to the lymphatic circulation. To speed up the clearance of macromolecules, borneol also stimulated lymphatic constriction by lowering the level of nitric oxide in the meninges. In addition, borneol stimulated lymphangiogenesis by increasing the levels of FOXC2, VEGFC, and LYVE-1 in the meninges, which promoted the clearance rates of macromolecules. Borneol improved meningeal lymphatic clearance not only for Aß but also for other macromolecular polymers (molecular weight in the range of 2 KD - 45 KD. Borneol ameliorated cognitive deficits and alleviated brain Aß burden in Aß-injected mice. Conclusions: Our findings not only provide a strategy to regulate lymphatic clearance pathways of macromolecules in the brain, but also new targets and ideas for treating neurodegenerative diseases like AD. Furthermore, our findings indicate that borneol is a promising therapeutic drug for AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/patologia , Óxido Nítrico/metabolismo , Encéfalo/metabolismo , Meninges/metabolismo , Meninges/patologia , Camundongos Transgênicos
18.
19.
Biomaterials ; 292: 121938, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36493715

RESUMO

L-arginine metabolism is essential for the activation, survival, and effector function of the T lymphocytes and critical in eliminating tumors via T-cell-mediated immunotherapy, such as immune checkpoint blockade (ICB). Unfortunately, efficient delivery of hydrophilic L-arginine to the tumor microenvironment (TME) has met tremendous difficulties because of the limited loading efficacy and rapid diffusion. Inspired by the small-molecule prodrug nanoassemblies with ultrahigh drug-loading, we screen out aromatic aldehydes compounds to be used as dynamic tags to decorate L-arginine (reversible imine). Nano-Arginine (ArgNP, 104 nm) was created based on dynamic tag-mediated self-assembly. Molecular dynamics simulations indicate that the driving force of this self-assembly process is intermolecular hydrogen bonds, π-π stacking, and cation-π interactions. Notably, ArgNP metabolic synergy with anti-PD-L1 antibody (aPDL1) can promote tumor-infiltrating T cells (3.3-fold than aPDL1), resulting in a tumor inhibition ratio of 2.6-fold than aPDL1. Besides, such a strategy efficiently reduces the myeloid-derived suppressor cells, increases the M1-macrophages against the tumor, and induces the production of memory T cells. Furthermore, this synergistic therapy effectively restrains lung metastasis and prolongs mouse survival (60% survival ratio). The study highlights the dynamic tags strategy with facility and advance to deliver L-arginine that can metabolically promote ICB therapy.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Camundongos , Animais , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Arginina , Microambiente Tumoral , Imunoterapia , Neoplasias/terapia , Linhagem Celular Tumoral
20.
Int J Hyperthermia ; 40(1): 2154576, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36535945

RESUMO

OBJECTIVE: This study compared the feasibility and efficacy of transabdominal ultrasound (TAU) and combined transabdominal and transvaginal ultrasound (TA/TV US)-guided percutaneous microwave ablation (PMWA) for uterine myoma (UM). METHOD: This study enrolled 73 patients with UM who underwent PMWA via the transabdominal ultrasound-guided (TA group) or the combined transabdominal and transvaginal ultrasound-guided (TA/TV group) approaches. The intraoperative supplementary ablation rates, postoperative immediate ablation rates, lesion reduction rates and other indicators three months postoperatively were compared between the groups. The display of the needle tip, endometrium, uterine serosa, rectum and myoma feeding vessels under the guidance of TAU, transvaginal ultrasound (TVU) and TA/TV US were evaluated in the TA/TV group. RESULTS: In the TA/TV group, the real-time position of the needle tip and the endometrium complete display rate of the same lesions with TVU guidance were significantly higher than those using TAU. TA/TV US guidance significantly improved the complete display rate of each indicator. The intraoperative supplementary ablation rate in the TA/TV group was lower than that in the TA group. Similarly, the postoperative immediate ablation and volume reduction rates of the lesions three months postoperatively were higher than those in the TA group, especially for lesions with a maximum diameter ≥6 cm. CONCLUSION: TA/TV US is an effective monitoring method that can be used to improve imaging display. Its use is recommended in patients with obesity, poor transabdominal ultrasound image quality and large myoma volumes.


Assuntos
Leiomioma , Mioma , Neoplasias Uterinas , Feminino , Humanos , Micro-Ondas , Leiomioma/cirurgia , Ultrassonografia , Ultrassonografia de Intervenção , Neoplasias Uterinas/cirurgia
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