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1.
Vet Comp Oncol ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090848

RESUMO

Canine lymphoma, the most prevalent haematopoietic tumour in dogs, presents significant challenges in veterinary oncology. This study investigates the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in small-sized dogs (≤10 kg) with multicentric lymphoma. In this retrospective study, we examined medical records and haematological data from 35 dogs to assess the association between NLR and two key outcomes: time-to-progression (TTP) and lymphoma-specific survival (LSS) using Cox proportional hazards models. Our findings revealed a significant correlation between elevated NLR and a worse prognosis, as evidenced by TTP (p = 0.005) and LSS (p = 0.001). NLR is linked to increased hazard ratios (HRs) for the time-to-progression rate (TTPR) at 180, 360 and 540 days (p = 0.001, p = 0.003 and p = 0.005, respectively) and the lymphoma-specific survival rate (LSSR) at the same intervals (p = 0.016, p = 0.001 and p = 0.001, respectively). Cutoff value of 3.764 for NLR was established, above which there is a significantly increased risk of early disease progression and decreased survival. Additionally, our analysis indicates that dogs with substage b exhibited earlier progression than those with substage a, evident in overall (p = 0.026) and TTPR at 180 days (p = 0.004), 360 days (p = 0.018), 540 days (p = 0.026) and LSSR at 180 days (p = 0.033). The results underscore the potential of NLR as a prognostic marker in cases of dogs ≤10 kg with multicentric lymphoma, suggesting that higher NLR is associated with a poorer prognosis.

2.
Biomaterials ; 312: 122736, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39121728

RESUMO

The resurgence of influenza viruses as a significant global threat emphasizes the urgent need for innovative antiviral strategies beyond existing treatments. Here, we present the development and evaluation of a novel super-multivalent sialyllactosylated filamentous phage, termed t-6SLPhage, as a potent entry blocker for influenza A viruses. Structural variations in sialyllactosyl ligands, including linkage type, valency, net charge, and spacer length, were systematically explored to identify optimal binding characteristics against target hemagglutinins and influenza viruses. The selected SLPhage equipped with optimal ligands, exhibited exceptional inhibitory potency in in vitro infection inhibition assays. Furthermore, in vivo studies demonstrated its efficacy as both a preventive and therapeutic intervention, even when administered post-exposure at 2 days post-infection, under 4 lethal dose 50% conditions. Remarkably, co-administration with oseltamivir revealed a synergistic effect, suggesting potential combination therapies to enhance efficacy and mitigate resistance. Our findings highlight the efficacy and safety of sialylated filamentous bacteriophages as promising influenza inhibitors. Moreover, the versatility of M13 phages for surface modifications offers avenues for further engineering to enhance therapeutic and preventive performance.

3.
Vet Res Commun ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39133399

RESUMO

The prevalence of chronic kidney disease (CKD) in dogs increases with age, and renal fibrosis is an important pathophysiological mechanism in this process. However, only a few drugs that can effectively inhibit fibrosis in the kidneys of dogs are currently available. In this study, we aimed to determine whether pirfenidone, a drug that has shown antifibrotic effects in various clinical studies, also exerts antifibrotic effects on canine renal tubular epithelial cells, Madin-Darby canine kidney cells (MDCK). To this end, we treated MDCK cells with various concentrations of pirfenidone, followed by transforming growth factor-beta1 (TGF-ß1) to stimulate fibrotic conditions. A cell viability assay was performed to determine the effect of pirfenidone on cell survival. Fibrosis-related markers and TGF-ß1 fibrotic pathway-related markers were assessed using qPCR, Western blot analysis and immunocytochemistry. A one-way analysis of variance (ANOVA) was performed, followed by Tukey's post-hoc test for multiple comparisons. Pirfenidone treatment significantly reduced the expression of profibrotic markers such as α-smooth muscle actin, fibronectin, and collagen. Additionally, it upregulated the expression of E-cadherin, an epithelial marker. Furthermore, pirfenidone effectively inhibited the phosphorylation of key factors involved in the TGF-ß1 signaling pathway, including Smad2/3 and ERK1/2. These results demonstrate that pirfenidone suppresses TGF-ß1-induced fibrosis in MDCK cells by attenuating epithelial-mesenchymal transition and the relevant signaling pathways.

4.
ACS Nano ; 18(33): 22298-22315, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39117621

RESUMO

A series of successes in RNA interference (RNAi) therapies for liver diseases using lipid nanoparticles and N-acetylgalactosamine have heralded a current era of RNA therapeutics. However, alternative delivery strategies are required to take RNAi out of the comfort zone of hepatocytes. Here we report SIRPα IgV/anti-CD47 siRNA (vS-siCD47) conjugates that selectively and persistently disrupt the antiphagocytic CD47/SIRPα axis in solid tumors. Conjugation of the SIRPα IgV domain protein to siRNAs enables tumor dash through CD47-mediated erythrocyte piggyback, primarily blocking the physical interaction between CD47 on cancer cells and SIRPα on phagocytes. After internalization of the vS-siCD47 conjugates within cancer cells, the detached free-standing anti-CD47 siRNAs subsequently attack CD47 through the RNAi mechanism. The dual-action approach of the vS-siCD47 conjugate effectively overcomes the "don't eat me" barrier and stimulates phagocyte-mediated tumor destruction, demonstrating a highly selective and potent CD47-blocking immunotherapy. This delivery strategy, employing IgV domain protein-siRNA conjugates with a dual mode of target suppression, holds promise for expanding RNAi applications beyond hepatocytes and advancing RNAi-based cancer immunotherapies for solid tumors.


Assuntos
Antígeno CD47 , RNA Interferente Pequeno , Receptores Imunológicos , Antígeno CD47/metabolismo , Antígeno CD47/química , Humanos , RNA Interferente Pequeno/química , Animais , Camundongos , Receptores Imunológicos/metabolismo , Neoplasias/terapia , Neoplasias/genética , Neoplasias/patologia , Antígenos de Diferenciação , Linhagem Celular Tumoral
5.
Sci Rep ; 14(1): 17507, 2024 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080400

RESUMO

Photodynamic and photothermal therapies are promising treatments for cancer, dermatological, and ophthalmological conditions. However, photodynamic therapy (PDT) is less effective in oxygen-deficient tumor environments. Combining PDT with photothermal therapy (PTT) can enhance oxygen supply and treatment efficacy. Inorganic PTT agents pose toxicity risks, limiting their clinical use despite their high performance. In this study, we developed a novel nanomedicine integrating an all-organic photothermal agent and an organic photosensitizer, creating a colocalized nanoplatform to enhance phototherapy efficacy in cancer treatment. PTT nanoparticles (NPs) were synthesized through a thermal phase transition of organic chromophores, demonstrating superior photothermal properties and photostability. Utilizing this nanoplatform, we devised 'Combi NPs' for combined PDT-PTT nanomedicine. Tests on A549 cancer cell lines have revealed that Combi NPs exhibit superior cytotoxicity and induce apoptosis in hypoxic conditions, outperforming PTT-only NPs. The all-organic Combi NPs show significant potential for clinical cancer phototherapy in hypoxic microenvironments, potentially mitigating long-term nanomedicine accumulation and associated toxicity.


Assuntos
Nanomedicina , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Fotoquimioterapia/métodos , Nanomedicina/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Nanopartículas/química , Células A549 , Terapia Fototérmica/métodos , Apoptose/efeitos dos fármacos , Terapia Combinada , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos
6.
Acta Pharm Sin B ; 14(3): 1428-1440, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38487005

RESUMO

Immune checkpoint blockade (ICB) therapy targeting PD-L1 via monoclonal antibody (mAb) has shown extensive clinical benefits in the diverse types of advanced malignancies. However, most patients are completely refractory to ICB therapy owing to the PD-L1 recycling mechanism. Herein, we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes (immune checkpoint blockade liposomes; ICB-LPs) to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor cells. The ICB-LPs are prepared by formulation of DC8,9PC with photo-polymerized diacetylenic moiety, 1,2-dipalmitoylphosphatidylcholine (DPPC) and anti-PD-L1 peptide (D-form NYSKPTDRQYHF)-conjugated DSPE-PEG2k (anti-PD-L1-DSPE-PEG2k) in a molar ratio of 45:45:10, followed by cross-linking of liposomal bilayer upon UV irradiation. The 10 mol% anti-PD-L1-DSPE-PEG2k incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7 ± 1.04 nm, showing a high stability in serum condition. Importantly, the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane, which are endocytosed with aim to deliver PD-L1 to the lysosomes, wherein the durable PD-L1 degradation is observed for 72 h, in contrast to anti PD-L1 mAbs showing the rapid PD-L1 recycling within 9 h. The in vitro co-culture experiments with CD8+ T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 axis. When ICB-LPs are intravenously injected into colon tumor-bearing mice, they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting, inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 degradation. Collectively, this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward the lysosomes instead of the recycling endosomes.

7.
Adv Mater ; 36(19): e2308837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38351715

RESUMO

As large molecular tertiary structures, some proteins can act as small robots that find, bind, and chaperone target protein clients, showing the potential to serve as smart building blocks in self-assembly fields. Instead of using such intrinsic functions, most self-assembly methodologies for proteins aim for de novo-designed structures with accurate geometric assemblies, which can limit procedural flexibility. Here, a strategy enabling polymorphic clustering of quaternary proteins, exhibiting simplicity and flexibility of self-assembling paths for proteins in forming monodisperse quaternary cage particles is presented. It is proposed that the enzyme protomer DegQ, previously solved at low resolution, may potentially be usable as a threefold symmetric building block, which can form polyhedral cages incorporated by the chaperone action of DegQ in the presence of protein clients. To obtain highly monodisperse cage particles, soft, and hence, less resistive client proteins, which can program the inherent chaperone activity of DegQ to efficient formations of polymorphic cages, depending on the size of clients are utilized. By reconstructing the atomic resolution cryogenic electron microscopy DegQ structures using obtained 12- and 24-meric clusters, the polymorphic clustering of DegQ enzymes is validated in terms of soft and rigid domains, which will provide effective routes for protein self-assemblies with procedural flexibility.


Assuntos
Estrutura Quaternária de Proteína , Serina Endopeptidases , Microscopia Crioeletrônica , Modelos Moleculares , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Serina Endopeptidases/química , Serina Endopeptidases/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo
8.
Bioact Mater ; 34: 164-180, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38343773

RESUMO

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

9.
J Mater Chem B ; 12(11): 2650-2669, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38353138

RESUMO

Light-triggered phototherapies, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have shown strong therapeutic efficacy with minimal invasiveness and systemic toxicity, offering opportunities for tumor-specific therapies. Phototherapies not only induce direct tumor cell killing, but also trigger anti-tumor immune responses by releasing various immune-stimulating factors. In recent years, conventional phototherapies have been combined with cancer immunotherapy as synergistic therapeutic modalities to eradicate cancer by exploiting the innate and adaptive immunity. These combined photoimmunotherapies have demonstrated excellent therapeutic efficacy in preventing tumor recurrence and metastasis compared to phototherapy alone. This review covers recent advancements in combined photoimmunotherapy, including photoimmunotherapy (PIT), PDT-combined immunotherapy, and PTT-combined immunotherapy, along with their underlying anti-tumor immune response mechanisms. In addition, the challenges and future research directions for light-triggered cancer immunotherapy are discussed.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fototerapia , Neoplasias/tratamento farmacológico , Imunoterapia
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 310: 123925, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38262297

RESUMO

Worldwide abuse of tetracycline (TC) seriously threatens environmental safety and human health. Metal-TC complexes formed by residual TC in the environment can also contribute to the spread of antibiotic resistance. Therefore, monitoring of TC residues is still required. Here, we report novel aggregation-induced emission carbon dots (AIE-Cdots) as nanoaggregate probes for the rapid and selective detection of TC residue. Riboflavin precursors with rotational functional groups led to the development of AIE-Cdots. The aggregation of AIE-Cdots was induced selectively for Al3+, amplifying the fluorescence signals owing to the restricted rotation of the side chains on the AIE-Cdot surface. The fluorescence signal of such Al3+-mediated nanoaggregates (Al3+-NAs) was further triggered by the structural fixation of TC at the Al3+ active sites, suggesting the formation of TC-coordinated Al3+-NAs. A linear correlation was observed in the TC concentration range of 0-10 µM with a detection limit of 42 nM. In addition, the strong Al3+ binding affinity of AIE-Cdots produced similar NAs and enhanced fluorescence signals in Al3+-TC mixtures. These AIE-Cdots-based nanoplatforms have a rapid response, good selectivity, and reliable accuracy for detecting TC or aluminum complexes, meeting the requirements for hazardous substance monitoring and removal in environmental applications.


Assuntos
Carbono , Compostos Heterocíclicos , Humanos , Carbono/química , Tetraciclina , Antibacterianos , Fluorescência , Corantes Fluorescentes/química , Espectrometria de Fluorescência
11.
Chemistry ; 30(5): e202302916, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-37902438

RESUMO

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox-related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker-based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs.


Assuntos
Envelhecimento , Corantes Fluorescentes , Camundongos , Animais , Corantes Fluorescentes/química , Espécies Reativas de Oxigênio/análise , Oxirredução , Células Sanguíneas/química
13.
Vet Med (Praha) ; 68(7): 293-298, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37982052

RESUMO

A 2-year-old, spayed female, Bichon Frise dog was presented with reluctance to exercise, back pain, and frequent sitting down. Multiple osteolysis, periosteal proliferation, and sclerosis of the vertebral endplates of T11-13 were observed in the radiography, computed tomography, and magnetic resonance imaging. The bacterial culture of the urine specimen, the polymerase chain reaction (PCR) of the blood, and the antibody tests were positive for Brucella canis. Accordingly, discospondylitis caused by B. canis was diagnosed and doxycycline was administered. The clinical signs resolved and the culture and PCR results were negative afterwards. Doxycycline was discontinued after 6 months. The clinical signs recurred 2 weeks later, and the combination treatment of doxycycline and enrofloxacin was initiated. Though no clinical signs were observed after 9 months and the bacterial cultures and PCR were negative, the antibody titre remained at 1 : 200 or more. The dog will continue taking antibiotics until the antibody titre drops. To the best of our knowledge, this is the first case report of a clinical infection of B. canis associated with canine discospondylitis in the Republic of Korea. Although the clinical signs of brucellosis might improve with antibiotic treatment, the disease cannot be cured due to Brucella's various strategies to evade host immune systems. Specifically, it can proliferate and replicate within the host cells, resulting in an environment that makes treatment less effective. Furthermore, owing to its zoonotic potential, owners and veterinarians should consider lifelong management or euthanasia.

14.
Front Vet Sci ; 10: 1255701, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026640

RESUMO

Administering more than 10 times the therapeutic dose of insulin is extremely rare in diabetic dogs and is life threatening with hypoglycemia and seizures if not accompanied by appropriate treatment. A 15-year-old, castrated male miniature poodle dog managed for diabetes presented with depression, disorientation, ataxia, and cluster seizures. The dog had been administered 11.1 U/kg of neutral protamine hegadorn (NPH) insulin (10 times the prescribed dose) 3 h before the onset of symptoms. Blood analysis revealed hypoglycemia, with a circulating glucose level of <50 mg/dL. To treat the hypoglycemia-induced seizures, dextrose was repeatedly administered intravenously. Repeated generalized seizures were treated with anticonvulsants and intermittent mannitol. Since refractory hypoglycemia persisted 24 h after the insulin overdose, it was decided to proceed with glucagon treatment (15-30 ng/kg/min titrated to the blood glucose level after a loading dose of 50 ng/kg intravenous bolus infusion). After 37 h of glucagon treatment, blood glucose levels stabilized. After entering a hyperglycemic state, NPH insulin was administered to manage insulin-dependent diabetes mellitus. This is the first case documented of successful treatment with glucagon, anticonvulsants and intermittent mannitol for refractory hypoglycemia and seizure caused by fatal insulin overdose. Thus, it has great clinical value in veterinary medicine.

15.
Materials (Basel) ; 16(18)2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37763439

RESUMO

The effect of the channel interface of top-gate InGaZnO (IGZO) thin film transistors (TFTs) on the electrical properties caused by exposure to various wet chemicals such as deionized water, photoresist (PR), and strippers during the photolithography process was studied. Contrary to the good electrical characteristics of TFTs including a protective layer (PL) to avoid interface damage by wet chemical processes, TFTs without PL showed a conductive behavior with a negative threshold voltage shift, in which the ratio of Ga and Zn on the IGZO top surface reduced due to exposure to a stripper. In addition, the wet process in photolithography increased oxygen vacancy and oxygen impurity on the IGZO surface. The photo-patterning process increased donor-like defects in IGZO due to organic contamination on the IGZO surface by PR, making the TFT characteristics more conductive. The introduction of ozone (O3) annealing after photo-patterning and stripping of IGZO reduced the increased defect states on the surface of IGZO due to the wet process and effectively eliminated organic contamination by PR. In particular, by controlling surface oxygens on top of the IGZO surface excessively generated with O3 annealing using UV irradiation of 185 and 254 nm, IGZO TFTs with excellent current-voltage characteristics and reliability could be realized comparable to IGZO TFTs containing PL.

16.
Front Vet Sci ; 10: 1189157, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720471

RESUMO

Introduction: Myxomatous mitral valve disease (MMVD) is the most common cause of heart failure in dogs, and assessing the risk of heart failure in dogs with MMVD is often challenging. Machine learning applied to electronic health records (EHRs) is an effective tool for predicting prognosis in the medical field. This study aimed to develop machine learning-based heart failure risk prediction models for dogs with MMVD using a dataset of EHRs. Methods: A total of 143 dogs with MMVD between May 2018 and May 2022. Complete medical records were reviewed for all patients. Demographic data, radiographic measurements, echocardiographic values, and laboratory results were obtained from the clinical database. Four machine-learning algorithms (random forest, K-nearest neighbors, naïve Bayes, support vector machine) were used to develop risk prediction models. Model performance was represented by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). The best-performing model was chosen for the feature-ranking process. Results: The random forest model showed superior performance to the other models (AUC = 0.88), while the performance of the K-nearest neighbors model showed the lowest performance (AUC = 0.69). The top three models showed excellent performance (AUC ≥ 0.8). According to the random forest algorithm's feature ranking, echocardiographic and radiographic variables had the highest predictive values for heart failure, followed by packed cell volume (PCV) and respiratory rates. Among the electrolyte variables, chloride had the highest predictive value for heart failure. Discussion: These machine-learning models will enable clinicians to support decision-making in estimating the prognosis of patients with MMVD.

17.
ACS Appl Mater Interfaces ; 15(37): 43455-43467, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37682242

RESUMO

To advance cancer treatment, we have developed a novel composite material consisting of conjugated polymer dots (CPDs) and Prussian blue (PB) particles, which were immobilized on, and encapsulated within, silica particles, respectively. The CPDs functioned as both a photosensitizer and a photodynamic agent, and the PB acted as a photothermal agent. The silica platform provided a biocompatible matrix that brought the two components into close proximity. Under laser irradiation, the fluorescence from the CPDs in the composite material enabled cell imaging and was subsequently converted to thermal energy by PB. This efficient energy transfer was accomplished because of the spectral overlap between the emission of donor CPDs and the absorbance of acceptor PB. The increase in local temperature in the cells resulted in a significant increase in the amount of reactive oxygen species (ROS) generated by CPDs, in which their independent use did not produce sufficient ROS for cancer cell treatment. To assess the impact of the enhanced ROS generation by the composite material, we conducted experiments using cancer cells under 532 nm laser irradiation. The results showed that with the increase in local temperature, the generated ROS increased by 30% compared with the control, which did not contain PB. When the silica-based composite material was positioned at the periphery of the tumor for 120 h, it led to a much slower tumor growth than other materials tested. By using a CPD-based photodynamic therapy platform, a new simplified approach to designing and preparing cancer treatments could be achieved, which included photothermal PB-assisted enhanced ROS generation using a single laser. This advancement opens up an exciting new opportunity for effective cancer treatment.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio , Neoplasias/tratamento farmacológico , Polímeros/farmacologia , Dióxido de Silício
18.
J Mater Chem B ; 11(31): 7344-7352, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37435627

RESUMO

Glutathione (GSH) is an essential molecule that plays a pivotal role in maintaining intracellular redox homeostasis, as well as other physiological processes. However, the chemical mechanisms underlying the GSH-induced processes remain insufficiently understood due to the lack of appropriate detection tools. Fluorescence GSH imaging can serve as a useful principle for the rapid, convenient, and non-destructive detection of GSH in living organisms. In this study, we developed a fluorescent GSH probe based on a linear, homoleptic Au(I) complex with two 1,3-diphenylbenzimidazolium carbene ligands. The Au(I) complex produced a fluorescence turn-on response to GSH. Fluorescence GSH signaling was characterized with a short response time of a few seconds. The rapid response was attributed to the displacement of the carbene ligand with GSH, which involved a labile inner-sphere coordination interaction. Finally, we demonstrated the biological utility of our GSH probe by unambiguously discriminating between different GSH levels in normal and senescent preadipocytes.


Assuntos
Glutationa , Glutationa/química , Ouro/química , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Sobrevivência Celular
19.
Adv Drug Deliv Rev ; 199: 114973, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37369262

RESUMO

RNA vaccines have demonstrated their ability to solve the issues posed by the COVID-19 pandemic. This success has led to the renaissance of research into mRNA and their nanoformulations as potential therapeutic modalities for various diseases. The potential of mRNA as a template for synthesizing proteins and protein fragments for cancer immunotherapy is now being explored. Despite the promise, the use of mRNA in cancer immunotherapy is limited by challenges, such as low stability against extracellular RNases, poor delivery efficiency to the target organs and cells, short circulatory half-life, variable expression levels and duration. This review highlights recent advances in chemical modification and advanced delivery systems that are helping to address these challenges and unlock the biological and pharmacological potential of mRNA therapeutics in cancer immunotherapy. The review concludes by discussing future perspectives for mRNA-based cancer immunotherapy, which holds great promise as a next-generation therapeutic modality.


Assuntos
COVID-19 , Neoplasias , Humanos , RNA Mensageiro , Pandemias , COVID-19/terapia , Imunoterapia , Proteínas
20.
World Neurosurg ; 175: e1307-e1314, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37164207

RESUMO

BACKGROUND: Unilateral laminotomy for bilateral decompression (ULBD) is a minimally invasive surgical technique widely used in patients with lumbar spinal stenosis and low-grade spondylolisthesis. However, few studies have investigated the long-term effects of the unilateral approach of ULBD on postoperative coronal imbalance, and the effect of additional discectomy on ULBD has not yet been evaluated in detail. METHODS: Sixty-one patients with lumbar spinal stenosis who underwent ULBD with or without discectomy were identified. The ULBD with discectomy group included 27 patients, and the ULBD without discectomy group included 34 patients. We analyzed the changes in various radiographic parameters, such as global lordosis (GL), segmental lordosis (SL), global coronal angle (GCA), segmental coronal angle (SCA), disc height (DH), global range of motion (GROM), and segmental range of motion (SROM) following the surgery and compared these parameters between the two groups. RESULTS: In patients who underwent ULBD with discectomy, segmental coronal angle (SCA) significantly decreased from 0.42 ± 4.41 (°±SD) preoperatively to -0.31 ± 4.87 postoperatively (P = 0.026), while disc height (DH) decreased from 8.80 ± 2.49 (mm ± SD) to 7.32 ± 2.60 (P < 0.001). These findings suggest a reduction in convexity as disc height decreased on the laminotomy side. However, the absolute SCA value tended to approach 0° postoperatively regardless of discectomy, indicating that the preoperative scoliosis has improved. In both groups, the lordotic angles and range of motion (ROM) parameters showed no changes before and after surgery. CONCLUSIONS: ULBD preserved lumbar lordosis and motion with or without discectomy during the 2-year follow-up period. Improvement in coronal balance was observed after ULBD regardless of discectomy, without significant negative effects on sagittal and coronal spine stability.


Assuntos
Lordose , Estenose Espinal , Humanos , Laminectomia/métodos , Descompressão Cirúrgica/métodos , Estenose Espinal/complicações , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Lordose/cirurgia , Resultado do Tratamento , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Discotomia , Estudos Retrospectivos
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