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1.
Biosens Bioelectron ; 267: 116737, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39243449

RESUMO

Exosomes have emerged as a promising noninvasive biomarker for early cancer diagnosis due to their ability to carry specific bioinformation related to cancer cells. However, accurate detection of trace amount of cancer-derived exosomes in complex blood remains a significant challenge. Herein, an ultra-highly sensitive SERS sensor, powered by the branched hybridization chain reaction (bHCR) and tetrahedral DNA-based trivalent aptamer (triApt-TDN), has been proposed for precise detection of cancer-derived exosomes. Taking gastric cancer SGC-7901 cells-derived exosomes as a test model, the triApt-TDNs were constructed by conjugating aptamers specific to mucin 1 (MUC1) protein with tetrahedral DNAs and subsequently immobilized on the surface of silver nanorods (AgNRs) arrays to create SERS-active sensing chips capable of specifically capturing exosomes overexpressing MUC1 proteins. The bHCR was further initiated by the trigger aptamers (tgApts) bound to exosomes, and as a result the SERS tags were assembled into AuNP network structures with abundant SERS hotspots. By optimizing the sensing conditions, the SERS sensor showed good performance in ultra-highly sensitive detection of target exosomes within 60 min detection time, with a broad response ranging of 1.44 to 1.44 × 104 particles·µL-1 and an ultralow limit of detection capable of detecting a single exosome in 2 µL sample. Furthermore, the SERS sensor exhibited good uniformity, repeatability and specificity, and capability to distinguish between gastric cancer (GC) patients and healthy controls (HC) through the detection of exosomes in clinical human serums, indicating its promising clinical potential for early diagnosis of gastric cancer.

2.
Bioorg Chem ; 151: 107710, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39146762

RESUMO

Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar2TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at ∼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC50 value of 0.45 µM, and phototherapeutic index of 25.8. Flow cytometry revealed that I3 could induce distinct cell apoptosis. In vivo studies revealed that compound I3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors.


Assuntos
Antineoplásicos , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Animais , Estrutura Molecular , Camundongos , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Verteporfina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/síntese química
3.
Nanomedicine (Lond) ; 19(18-20): 1643-1658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011648

RESUMO

Aim: A study of the enhancement of photodynamic activities of pyropheophorbide-a using PG-Ag-PPa nanoconjugates.Materials & methods: The nanoconjugates were formulated from silver nanoparticles and PPa via amide linkage, then characterized, and their photodynamic activities were examined.Results: The nanoconjugates displayed a higher rate of reactive oxygen species generation, commendable cellular uptake by Eca-109 cancer cells, higher photocytotoxicity toward the cancer cells and better bio-safety. They revealed strong antibacterial activity against Escherichia coli following internal reactive oxygen species generation and membrane disintegration. The in vivo anticancer studies confirmed higher cytotoxicity of the nanoconjugates toward cancer cells and better safety than PPa.Conclusion: Therefore, PG-Ag-PPa nanoconjugates could be considered potential nano photosensitizers for photodynamic therapy of tumors and bacterial infection with good bio-safety.


[Box: see text].


Assuntos
Antibacterianos , Antineoplásicos , Clorofila , Escherichia coli , Nanoconjugados , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Prata , Prata/química , Prata/farmacologia , Clorofila/análogos & derivados , Clorofila/farmacologia , Clorofila/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Fotoquimioterapia/métodos , Escherichia coli/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Animais , Nanoconjugados/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas Metálicas/química , Camundongos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico
4.
ACS Med Chem Lett ; 15(7): 1109-1117, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39015270

RESUMO

To discover effective photosensitizers for photodynamic therapy (PDT), a series of new meso-tetraphenyltetrabenzoporphyrin (m-Ph4TBP) derivatives were designed, prepared, and characterized. All m-Ph4TBPs own two characteristic absorption bands in the range of 450-500 and 600-700 nm and have the ability to generate singlet oxygen upon photoexcitation. Most of the m-Ph4TBPs demonstrated high photoactivity, among which compounds I4, I6, I12, and I13 induced apoptosis and also exhibited excellent photodynamic activities in vivo. Nonetheless, the liver organs of the I4 and I6-PDT groups showed clear calcifications, whereas the liver tissues of the other PDT groups showed no calcification. It was indicated that compared to phenolic m-Ph4TBPs, glycol m-Ph4TBPs exhibited superior biological safety in mice. According to comprehensive evaluations, m-Ph4TBP I12 displayed excellent photodynamic antitumor efficacy and biological safety and can be regarded as a promising antitumor drug candidate.

5.
Signal Transduct Target Ther ; 9(1): 190, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039046

RESUMO

The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6-3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.


Assuntos
Administração Intranasal , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Animais , Camundongos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina A/imunologia , Imunoglobulina A/sangue , Imunoglobulina A/genética , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Feminino , Vetores Genéticos/imunologia , Vetores Genéticos/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Imunoglobulina A Secretora/imunologia , Adenoviridae/genética , Adenoviridae/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Masculino
6.
Talanta ; 278: 126565, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39018762

RESUMO

Bacteria infections pose a serious threat to public health, and it is urgent to develop facile and accurate detection methods. To meet the important need, a potable and high-sensitive surface enhanced Raman scattering (SERS) biosensor based on aptamer recognition and catalytic hairpin assembly (CHA) signal amplification was proposed for point-of-care detection of Staphylococcus aureus (S. aureus). The SERS biosensor contains three parts: recognition probes, SERS sensing chip, and SERS tags. The feasibility of the strategy was verified by gel electrophoresis, and the one-step test route was optimized. The bacteria SERS biosensor has a good linear relationship ranging from 10 to 107 CFU mL-1 with high sensitivity low to 5 CFU mL-1, and shows excellent specificity, uniformity, and repeatability on S. aureus identification and enumeration, which can distinguish S. aureus from other bacteria. The SERS biosensor shows a good recovery rate (95.73 %-109.65 %) for testing S. aureus spiked in milk, and has good practicability for detecting S. aureus infected mouse wound, which provides a facile and reliable approach for detection of trace bacteria in the real samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Análise Espectral Raman , Staphylococcus aureus , Staphylococcus aureus/isolamento & purificação , Técnicas Biossensoriais/métodos , Aptâmeros de Nucleotídeos/química , Análise Espectral Raman/métodos , Animais , Leite/microbiologia , Leite/química , Limite de Detecção , Camundongos , Nanopartículas Metálicas/química , Catálise , Ouro/química , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia
7.
Front Bioeng Biotechnol ; 12: 1355617, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846802

RESUMO

Gliding is a crucial phase in swimming, yet the understanding of fluid force and flow fields during gliding remains incomplete. This study analyzes gliding through Computational Fluid Dynamics simulations. Specifically, a numerical model based on the Smoothed Particle Hydrodynamics (SPH) method for flow-object interactions is established. Fluid motion is governed by continuity, Navier-Stokes, state, and displacement equations. Modified dynamic boundary particles are used to implement solid boundaries, and steady and uniform flows are generated with inflow and outflow conditions. The reliability of the SPH model is validated by replicating a documented laboratory experiment on a circular cylinder advancing steadily beneath a free surface. Reasonable agreement is observed between the numerical and experimental drag force and lift force. After the validation, the SPH model is employed to analyze the passive drag, vertical force, and pitching moment acting on a streamlined gliding 2D swimmer model as well as the surrounding velocity and vorticity fields, spanning gliding velocities from 1 m/s to 2.5 m/s, submergence depths from 0.2 m to 1 m, and attack angles from -10° to 10°. The results indicate that with the increasing gliding velocity, passive drag and pitching moment increase whereas vertical force decreases. The wake flow and free surface demonstrate signs of instability. Conversely, as the submergence depth increases, there is a decrease in passive drag and pitching moment, accompanied by an increase in vertical force. The undulation of the free surface and its interference in flow fields diminish. With the increase in the attack angle, passive drag and vertical force decrease whereas pitching moment increases, along with the alteration in wake direction and the increasing complexity of the free surface. These outcomes offer valuable insights into gliding dynamics, furnishing swimmers with a scientific basis for selecting appropriate submergence depth and attack angle.

8.
Front Microbiol ; 15: 1386891, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881666

RESUMO

Introduction: Infection with SARS-CoV-2 begins in the upper respiratory tract and can trigger the production of mucosal spike-specific secretory IgA (sIgA), which provides protection against reinfection. It has been recognized that individuals with high level of nasal spike-specific IgA have a lower risk of reinfection. However, mucosal spike-specific sIgA wanes over time, and different individuals may have various level of spike-specific sIgA and descending kinetics, leading to individual differences in susceptibility to reinfection. A method for detecting spike-specific sIgA in the nasal passage would be valuable for predicting the risk of reinfection so that people at risk can have better preparedness. Methods: In this study, we describe the development of a colloidal gold-based immunochromatographic (ICT) strip for detecting SARS-CoV-2 Omicron spike-specific sIgA in nasal mucosal lining fluids (NMLFs). Results: The ICT strip was designed to detect 0.125 µg or more spike-specific sIgA in 80 µL of NMLFs collected using a nasal swab. Purified nasal sIgA samples from individuals who recently recovered from an Omicron BA.5 infection were used to demonstrate that this ICT strip can specifically detect spike-specific sIgA. The signal levels positively correlated with neutralizing activities against XBB. Subsequent analysis revealed that people with low or undetectable levels of spike-specific sIgA in the nasal passage were more susceptible to SARS-CoV-2 reinfection. Conclusions: This nasal spike-specific sIgA ICT strip provides a non-invasive, rapid, and convenient method to assess the risk of reinfection for achieving precision preparedness.

9.
Plant Physiol Biochem ; 213: 108826, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38908351

RESUMO

Rice production is threatened by heavy metal stress. The use of multi-walled carbon nanotubes (MWCNTs) in agriculture has been reported in previous studies. We aimed to quantify the impact of MWCNTs on the growth and physiological characteristics of scented rice under cadmium (Cd) and lead (Pb) stresses. Therefore, a pot experiment was conducted, two scented rice varieties Yuxiangyouzhan and Xiangyaxiangzhan were used as materials grown under different concentrations of MWCNTs (0, 100, and 300 mg kg-1 recorded as CK, CNPs100, and CNPs300, respectively). The yield, antioxidant response, and rhizosphere microbial community of scented rice were studied. The results showed that compared with the CK treatment, the CNPs100 and CNPs300 treatments increased leaf dry weight by 17.95%-56.22% at the heading stage, and the H2O2 content in leaves decreased significantly by 36.64%-42.27% at the maturity stage. Under CNPs100 treatment, the grain yield of two scented rice varieties increased significantly by 17.54% and 27.40%, respectively. The MWCNTs regulated the distribution of the Cd and Pb in different plant tissues. The content of Cd (0.11-0.20 mg kg-1) and Pb (0.01-0.04 mg kg-1) in grain were at a safety level (<0.2 mg kg-1). Moreover, MWCNTs increased soil microbial community abundance and altered community composition structure under Cd-Pb stress, which in turn improved agronomic traits and quality of scented rice. Overall, this study suggested that the application of MWCNTs regulates the growth, yield, physiological response, and soil microbial community, the genotypes response effect of scented rice to MWCNTs is needed further studied.


Assuntos
Antioxidantes , Cádmio , Chumbo , Nanotubos de Carbono , Oryza , Rizosfera , Oryza/microbiologia , Oryza/efeitos dos fármacos , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Cádmio/toxicidade , Cádmio/metabolismo , Chumbo/metabolismo , Chumbo/toxicidade , Antioxidantes/metabolismo , Microbiota/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Microbiologia do Solo , Estresse Fisiológico/efeitos dos fármacos
10.
Aquat Toxicol ; 272: 106942, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788458

RESUMO

The gut microbiome is crucial in maintaining fish health homeostasis. Disinfectants can kill important pathogens and disinfect fish eggs, yet their effect on the immune pathways and intestinal microbiome in healthy fish remains unknown. In this study, we investigated the effects of two disinfectants on the transcriptome profiles, immunological response, and gut microbiota dynamics of grass carp over a four-week trial. In particular, aquatic water was disinfected with 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine. We found that glutaraldehyde and povidone-iodine induced gut antioxidant system and depressed the function of grass carp digestive enzymes. The results of the 16S rDNA high-throughput sequencing identified a reduction in the diversity of grass carp gut microbiota following the disinfectant treatment. Moreover, transcriptome profiling revealed that disinfectant exposure altered the immune-related pathways of grass carp and inhibited the expression of inflammation and tight junction related genes. Finally, the histopathological observation and apoptosis detection results suggested that the long-term diet of disinfectant destroyed intestinal structural integrity and promoted apoptosis. In conclusion, long-term exposure to disinfectants was observed to reduce oxidation resistance, suppress the immune response, dysbiosis of the intestinal flora, and resulted in increasing the apoptosis in intestinal of grass carp.


Assuntos
Carpas , Desinfetantes , Microbioma Gastrointestinal , Poluentes Químicos da Água , Animais , Carpas/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Desinfetantes/toxicidade , Poluentes Químicos da Água/toxicidade , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Intestinos/microbiologia , Transcriptoma/efeitos dos fármacos
11.
China CDC Wkly ; 6(15): 312-317, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38736993

RESUMO

What is already known about this topic?: Mucosal IgA plays a crucial role in host immunity against respiratory viruses. Recent studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. However, a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019 (COVID-19) pandemic is yet to be conducted. What is added by this report?: In our study involving 3,421 participants, we documented IgA responses subsequent to SARS-CoV-2 infection. A significant proportion of individuals sustained increased levels of IgA for over six months. These levels were also observed in individuals with prior infections who underwent asymptomatic reinfections, indicating an active production of IgA antibodies. Further, individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after recovery. What are the implications for public health practice?: IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 infection. These insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

12.
J Robot Surg ; 18(1): 167, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592362

RESUMO

This meta-analysis was conducted to evaluate and contrast the effectiveness of robotic-assisted and laparoscopic colorectal surgery in the treatment of obese patients. In February 2024, we carried out an exhaustive search of key global databases including PubMed, Embase, and Google Scholar, limiting our focus to studies published in English and Chinese. We excluded reviews, protocols lacking published results, articles derived solely from conference abstracts, and studies not relevant to our research objectives. To analyze categorical variables, we utilized the Cochran-Mantel-Haenszel method along with random-effects models, calculating inverse variances and presenting the outcomes as odds ratios (ORs) along with their 95% confidence intervals (CIs). Statistical significance was determined when p values were less than 0.05. In our final meta-analysis, we included eight cohort studies, encompassing a total of 5,004 patients. When comparing the robotic surgery group to the laparoscopic group, the findings revealed that the robotic group experienced a longer operative time (weighted mean difference (WMD) = 37.53 min, 95% (CI) 15.58-59.47; p = 0.0008), a shorter hospital stay (WMD = -0.68 days, 95% CI -1.25 to -0.10; p = 0.02), and reduced blood loss (WMD = -49.23 mL, 95% CI -64.31 to -34.14; p < 0.00001). No significant differences were observed between the two groups regarding overall complications, conversion rates, surgical site infections, readmission rates, lymph node yield, anastomotic leakage, and intestinal obstruction. The results of our study indicate that robot-assisted colorectal surgery offers benefits for obese patients by shortening the length of hospital stay and minimizing blood loss when compared to laparoscopic surgery. Nonetheless, it is associated with longer operation times and shows no significant difference in terms of overall complications, conversion rates, rehospitalization rates, and other similar metrics.


Assuntos
Cirurgia Colorretal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Obesidade/complicações , Procedimentos Cirúrgicos Robóticos/métodos
13.
J Med Chem ; 67(7): 5866-5882, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38556760

RESUMO

MERTK and AXL are members of the TAM (TYRO3, AXL, MERTK) family of receptor tyrosine kinases that are aberrantly expressed and have been implicated as therapeutic targets in a wide variety of human tumors. Dual MERTK and AXL inhibition could provide antitumor action mediated by both direct tumor cell killing and modulation of the innate immune response in some tumors such as nonsmall cell lung cancer. We utilized our knowledge of MERTK inhibitors and a structure-based drug design approach to discover a novel class of macrocyclic dual MERTK/AXL inhibitors. The lead compound 43 had low-nanomolar activity against both MERTK and AXL and good selectivity over TYRO3 and FLT3. Its target engagement and selectivity were also confirmed by NanoBRET and cell-based MERTK and AXL phosphorylation assays. Compound 43 had excellent pharmacokinetic properties (large AUC and long half-life) and mediated antitumor activity against lung cancer cell lines, indicating its potential as a therapeutic agent.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , c-Mer Tirosina Quinase/metabolismo , Receptor Tirosina Quinase Axl , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral
14.
Artigo em Inglês | MEDLINE | ID: mdl-38662912

RESUMO

The conventional von Neumann architecture has proven to be inadequate in keeping up with the rapid progress in artificial intelligence. Memristors have become the favored devices for simulating synaptic behavior and enabling neuromorphic computations to address challenges. An artificial synapse utilizing the perovskite structure PbHfO3 (PHO) has been created to tackle these concerns. By employing the sol-gel technique, a ferroelectric film composed of Au/PHO/FTO was created on FTO/glass for the purpose of this endeavor. The artificial synapse is composed of Au/PHO/FTO and exhibits learning and memory characteristics that are similar to those observed in biological neurons. The recognition accuracy for both MNIST and Fashion-MNIST data sets saw an increase, reaching 92.93% and 76.75%, respectively. This enhancement resulted from employing a convolutional neural network architecture and implementing an improved stochastic adaptive algorithm. The presented findings showcase a viable approach to achieve neuromorphic computation by employing artificial synapses fabricated with PHO.

15.
J Endovasc Ther ; : 15266028241241248, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38590247

RESUMO

PURPOSE: The purpose of this study is to assess the efficacy and safety of cilostazol prescription in patients with femoropopliteal peripheral artery disease (PAD) after endovascular therapy (EVT). MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of all studies reporting the outcomes of cilostazol after femoropopliteal EVT of PAD up to September 2022. Clinical outcomes of interest included primary patency, in-stent restenosis (ISR), vessel re-occlusion, freedom from target lesion revascularization (TLR), repeat revascularization, all-cause mortality, amputation, major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs), and bleeding complication. RESULTS: A total of 4 randomized controlled trials (RCTs) and 8 observational studies containing a total of 4898 patients met the inclusion criteria and were included in this systematic review and meta-analysis. We found that the use of cilostazol was associated with higher primary patency after femoropopliteal artery EVT (odds ratio [OR]=1.67, 95% confidence interval [CI]=1.50-1.87, p<0.001, I2=33.2%), a lower risk of ISR (OR=0.43, 95% CI=0.29-0.63, p<0.001, I2=37.6%), repeat revascularization (OR=0.43, 95% CI=0.24-0.76, p<0.005, I2=27.4%), and vessel re-occlusion (OR=0.59, 95% CI=0.38-0.93, p<0.05, I2=0%). There was an increase in freedom from TLR rate (OR=2.19, 95% CI=1.58-3.05, p<0.001, I2=0%), as well as a reduction in the occurrence of MALEs (OR=0.50, 95% CI=0.29-0.85, p<0.05, I2=0%). However, there was no significant difference in amputation, MACEs, all-cause mortality, and major bleeding complications. Subgroup analysis showed that cilostazol treatment in patients with femoropopliteal drug-eluting stents (DES) implantation remained associated with higher primary patency and a lower risk of ISR. CONCLUSIONS: After EVT of femoropopliteal artery lesions, additional oral cilostazol enhances primary patency, reduces the occurrences of ISR and vessel re-occlusion, diminishes the risks associated with MALEs, lowers the need for repeat revascularization, and increases freedom from TLR rates. However, it does not impact amputation, MACEs, all-cause mortality, or major bleeding complications. These findings suggest cilostazol as a potentially safe and effective adjunct therapy in patients with femoropopliteal PAD after EVT. CLINICAL IMPACT: After undergoing endovascular therapy (EVT) for femoropopliteal artery lesions, the addition of cilostazol to antiplatelet therapy can significantly improve primary patency, reducing the incidence of in-stent restenosis, repeat revascularization, vessel re-occlusion, and major adverse limb events while increasing freedom from target lesion revascularization rate. The simultaneous use of drug-eluting stents in the femoropopliteal artery lesions, combined with cilostazol, potentially results in a synergistic anti-stenotic effect. This therapeutic approach does not appear to be associated with an increased risk of major bleeding events or all-cause mortality. These findings provide additional evidence supporting the treatment of anti-stenosis in patients with femoropopliteal artery lesions after EVT.

16.
Small ; 20(30): e2308562, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38441369

RESUMO

Diagnosis and treatment of tumor especially drug-resistant tumor remains a huge challenge, which requires intelligent nanomedicines with low toxic side effects and high efficacy. Herein, deformable smart DNA nanomachines are developed for synergistic intracellular cancer-related miRNAs imaging and chemo-gene therapy of drug-resistant tumors. The tetrahedral DNA framework (MA-TDNA) with fluorescence quenched component and five antennas is self-assembled first, and then DOX molecules are loaded on the MA-TDNAs followed by linking MUC1-aptamer and Mcl-1 siRNA to the antennas of MA-TDNA, so that the apt-MA-TDNA@DOX-siRNA (DNA nanomachines) is constructed. The DNA nanomachine can respond to two tumor-related miRNAs in vitro and in vivo, which can undergo intelligent miRNA-triggered opening of the framework, resulting in the "turn on" of the fluorescence for sensitively and specifically sensing intracellular miRNAs. Meanwhile, both miRNA-responded rapid release and pH-responded release of DOX are achieved for chemotherapy of tumor. In addition, the gene therapy of the DNA nanomachines is achieved due to the miRNA-specific capture and the RNase H triggered release of Mcl-1 siRNA. The DNA nanomachines intergrading both tumor imaging and chemo-gene therapy in single nanostructures realized efficient tumor-targeted, image-guided, and microenvironment-responsive tumor diagnosis and treatment, which provides a synergetic antitumor effect on drug-resistant tumor.


Assuntos
DNA , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Terapia Genética , MicroRNAs , MicroRNAs/genética , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Terapia Genética/métodos , DNA/química , Animais , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Neoplasias/genética , RNA Interferente Pequeno , Linhagem Celular Tumoral , Espaço Intracelular/metabolismo
17.
Biosens Bioelectron ; 253: 116196, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38467101

RESUMO

Developing rapid, accurate and convenient nucleic acid diagnostic techniques is essential for the prevention and control of contagious diseases that are prone to gene mutations and may have homologous sequences, especially emerging infectious diseases such as the SARS-CoV-2 pandemic. Herein, a one-pot SERS assay integrating isothermal cascade signal amplification strategy (i.e., CRISPR/Cas13a system (Cas13a) and catalytic hairpin assembly (CHA), Cas13a-CHA) and SERS-active silver nanorods (AgNRs) sensing chips was proposed for rapid and accurate detection of disease-related nucleic acids. Taking SARS-CoV-2 RNA assay as a model, the Cas13a-CHA based SERS sensing strategy can achieve ultra-high sensitivity low to 5.18 × 102 copies·mL-1 within 60 min, and excellent specificity, i.e., not only the ability to identify SARS-CoV-2 RNA from gene mutations, but also incompatibility with coronaviruses such as severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and other respiratory viruses. The proposed Cas13a-CHA based SERS assay for SARS-CoV-2 RNA has satisfactory sensitivity, specificity, uniformity, and repeatability, and can be easily expanded and universalized for screening different viruses, which is expected to promise as a crucial role for diagnosis of disease-related nucleic acids in various medical application scenarios.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , RNA Viral/genética , Bioensaio , Técnicas de Amplificação de Ácido Nucleico
18.
ACS Appl Mater Interfaces ; 16(8): 10344-10351, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38350064

RESUMO

The outstanding photoelectric properties of perovskites demonstrate extreme promise for application in X-ray detection. However, the soft lattice of the perovskite results in severe ionic migration for three-dimensional materials, limiting the operation stability of perovskite X-ray detectors. Although ligand-decorated nanocrystals (NCs) exhibit significantly higher stability than three-dimensional perovskites, defects remaining on the interface of NCs could still trigger halide migration under a high bias due to the incomplete ligand decoration. Furthermore, it is still challenging to realize sufficient thickness of absorption layers based on NCs for X-ray detectors through traditional methods. Herein, we develop a centimeter-size and millimeter-thick wafer based on CsPbBr3 NCs through isostatic pressing for X-ray detectors, in which the interfacial defects of NCs are remedied by CsPb2Br5 during aging of wafer in ambient humidity. The wafer shows outstanding sensitivity (200 µC Gyair-1 cm-2) and ultralow dark current drift (1.78 × 10-8 nA cm-1 s-1 V-1 @ 400 V cm-1). Moreover, it shows storage stability with negligible performance degradation for 60 days in ambient humidity. Thus, aging perovskite NC wafers for X-ray detection holds huge potential for next-generation X-ray imaging plates.

19.
ACS Appl Mater Interfaces ; 16(10): 12844-12852, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38416069

RESUMO

High-energy radiation detectors with a good imaging resolution, fast response, and high sensitivity are desired to operate at a high electric field. However, strong ion migration triggered by electrochemical reactions at the interface between a high-potential electrode and an organic-inorganic hybrid perovskite limits the stability of radiation detectors under a high electric field. Herein, we demonstrate that such ion migration could be effectively suppressed in devices with a Ti cathode, even at a high electric field of 50 V mm-1, through time-of-flight secondary-ion mass spectrometry. X-ray photoelectron spectroscopy illustrates that Ti-N bonds formed at the interface of MAPbBr3 perovskite single crystals/Ti electrode effectively inhibit the electrochemical reaction in organic-inorganic hybrid perovskite devices and ultimately improve the operating stability under a high electric field. The device with a Ti electrode reaches a high sensitivity of 96 ± 1 mC Gyair-1 cm-2 and a low detection limit of 2.8 ± 0.3 nGy s-1 under hard X-ray energy.

20.
Ecotoxicol Environ Saf ; 272: 116078, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38335575

RESUMO

Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.


Assuntos
Carpas , Desinfetantes , Animais , Humanos , Povidona-Iodo/toxicidade , Glutaral/toxicidade , Receptores Ativados por Proliferador de Peroxissomo , Fígado , Hepatócitos , Desinfetantes/toxicidade , Apoptose
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