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1.
Nat Commun ; 15(1): 8586, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39362879

RESUMO

The limited efficacy of cancer immunotherapy occurs due to the lack of spatiotemporal orchestration of adaptive immune response stimulation and immunosuppressive tumor microenvironment modulation. Herein, we report a nanoplatform fabricated using a pH-sensitive triblock copolymer synthesized by reversible addition-fragmentation chain transfer polymerization enabling in situ tumor vaccination and tumor-associated macrophages (TAMs) polarization. The nanocarrier itself can induce melanoma immunogenic cell death (ICD) via tertiary amines and thioethers concentrating on mitochondria to regulate metabolism in triggering endoplasmic reticulum stress and upregulating gasdermin D for pyroptosis as well as some features of ferroptosis and apoptosis. After the addition of ligand cyclic arginine-glycine-aspartic acid (cRGD) and mannose, the mixed nanocarrier with immune adjuvant resiquimod encapsulation can target B16F10 cells for in situ tumor vaccination and TAMs for M1 phenotype polarization. In vivo studies indicate that the mixed targeting nanoplatform elicits tumor ICD, dendritic cell maturation, TAM polarization, and cytotoxic T lymphocyte infiltration and inhibits melanoma volume growth. In combination with immune checkpoint blockade, the survival time of mice is markedly prolonged. This study provides a strategy for utilizing immunoactive materials in the innate and adaptive immune responses to augment cancer therapy.


Assuntos
Morte Celular Imunogênica , Imunoterapia , Melanoma Experimental , Nanopartículas , Polímeros , Animais , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos , Imunoterapia/métodos , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Nanopartículas/química , Polímeros/química , Linhagem Celular Tumoral , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Feminino , Portadores de Fármacos/química , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Humanos , Apoptose/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-39370493

RESUMO

PURPOSE: Teleoperated Interventional Robotic systems (TIRs) are developed to reduce radiation exposure and physical stress of the physicians and enhance device manipulation accuracy and stability. Nevertheless, TIRs are not widely adopted, partly due to the lack of intuitive control interfaces. Current TIR interfaces like joysticks, keyboards, and touchscreens differ significantly from traditional manual techniques, resulting in a shallow, longer learning curve. To this end, this research introduces a novel control mechanism for intuitive operation and seamless adoption of TIRs. METHODS: An off-the-shelf medical torque device augmented with a micro-electromagnetic tracker was proposed as the control interface to preserve the tactile sensation and muscle memory integral to interventionalists' proficiency. The control inputs to drive the TIR were extracted via real-time motion mapping of the interface. To verify the efficacy of the proposed control mechanism to accurately operate the TIR, evaluation experiments using industrial grade encoders were conducted. RESULTS: A mean tracking error of 0.32 ± 0.12 mm in linear and 0.54 ± 0.07° in angular direction were achieved. The time lag in tracking was found to be 125 ms on average using pade approximation. Ergonomically, the developed control interface is 3.5 mm diametrically larger, and 4.5 g. heavier compared to traditional torque devices. CONCLUSION: With uncanny resemblance to traditional torque devices while maintaining results comparable to state-of-the-art commercially available TIRs, this research successfully provides an intuitive control interface for potential wider clinical adoption of robot-assisted interventions.

3.
Adv Healthc Mater ; : e2400030, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113347

RESUMO

Programmed death (PD) 1/PD ligand 1 (PDL1) inhibitors are immune checkpoint inhibitors (ICIs) that may facilitate HER2-positive breast cancer treatment; however, their clinical efficacy remains elusive. Oxygen-enhanced photodynamic therapy (PDT) increases immunogenic cell death (ICD), providing a promising strategy to render the tumor microenvironment more sensitive to the ICIs. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O2) obtained using nanobubbles (NBs) water for oxygen delivery in vivo can facilitate enhanced PDT. Here, dual-receptor targeted Lipo-NBs-O2 (DRT@Lipo-NBs-O2) is prepared by modifying Lipo-NBs-O2 with anti-PDL1 scFv and the fusion protein anti-HER2 scFv-tandem-repeat cytochrome c (anti-HER2-nCytc). Copper phthalocyanine is the photosensitizer (PS). DRT@Lipo-PS-NBs-O2 plus near-infrared irradiation leads to robust ICD induction, increasing DC activation and CD8+ T-cell numbers. Modification with anti-PDL1 scFv improves tumor distribution of DRT@Lipo-PS-NBs-O2 and plays the ICI role, invigorating CD8+ T cells and boosting the effects of immunotherapy. Oxygen supplied through DRT@Lipo-PS-NBs-O2 reduces P-glycoprotein expression. Enhanced PDT and Cytc can cause tumor cell death, thereby reducing the immune burden. Under dual receptor targeting and laser local irradiation, tumor cells become subject to the combination effects of PDT, ICD, ICIs, and apoptosis; this effectively suppresses tumor growth and metastasis. Lipo-NBs-O2 affords a combination of oxygen delivery and multidrug therapy to alleviate HER2-positive breast cancer.

4.
Inorg Chem ; 63(32): 15134-15143, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39074382

RESUMO

Gossypol (Gsp) and antibiotics present in water bodies become organic pollutants that are harmful to human health and the ecological environment. Accurate and effective detection of these pollutants has far-reaching significance in many fields. A new three-dimensional metal-organic framework (MOF), {[Eu3(L)2(HCOO-)(H2O)3]·2H2O·2DMF}n (Eu-MOF), was synthesized from 3,5-bis(2,4-dicarboxylphenyl)nitrobenzene (H4L) ligand and Eu3+ via the solvothermal method in this paper. The Eu-MOF demonstrates strong red fluorescence and can remain stable in different pH solutions. The MOF fluorescence probe could detect organic pollutants through the "shut-off" effect, with a fast response speed and a low detection limit [Gsp, nitrofurantoin (NFT), and nitrofurazone (NFZ) for 0.43, 0.38, and 0.41 µM, respectively]. During the testing process, Eu-MOF exhibited good selectivity and recoverability. Furthermore, the mechanism of fluorescence quenching was investigated, and the recoveries were also good in real samples. This paper introduced a deep learning model to recognize the fluorescence images, a portable intelligent logic detector designed for real-time detection of Gsp by logic gate strategy, and an anticounterfeiting mark prepared based on inkjet printing. Importantly, this work provides a new way of thinking for the detection of organic pollutants in water with high sensitivity and practicality by combining the fluorescence probe with machine learning and logical judgment.


Assuntos
Antibacterianos , Európio , Corantes Fluorescentes , Gossipol , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Európio/química , Antibacterianos/análise , Antibacterianos/química , Gossipol/análise , Gossipol/química , Poluentes Químicos da Água/análise , Nitrofuranos/análise , Espectrometria de Fluorescência , Estrutura Molecular , Limite de Detecção
5.
Ecotoxicol Environ Saf ; 279: 116447, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38759537

RESUMO

BACKGROUND AND OBJECTIVES: Many studies suggested that short-term exposure to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM2.5 and PM2.5-10 on various types of cerebrovascular disease. METHODS: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season. RESULTS: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10 µg/m3 rise in PM2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10 µg/m3 rise in PM2.5-10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season. CONCLUSIONS: Short-term exposures to both PM2.5 and PM2.5-10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae.


Assuntos
Poluentes Atmosféricos , Transtornos Cerebrovasculares , Estudos Cross-Over , Material Particulado , Material Particulado/análise , Material Particulado/toxicidade , Humanos , Masculino , China/epidemiologia , Feminino , Pessoa de Meia-Idade , Idoso , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/induzido quimicamente , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Tamanho da Partícula , Idoso de 80 Anos ou mais , Adulto , Estações do Ano
6.
Adv Healthc Mater ; 13(16): e2303568, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319010

RESUMO

High reactive oxygen species (ROS) levels in tumor microenvironment (TME) impair both immunogenic cell death (ICD) efficacy and T cell activity. Furthermore, tumor escapes immunosurveillance via programmed death-1/programmed death ligand-1 (PD-L1) signal, and the insufficient intracellular hydrogen peroxide weakens ferroptosis efficacy. To tackle the above issues, a glutathione (GSH)/ROS/pH triple-responsive prodrug nanomedicine that encapsulates Fe2O3 nanoparticle via electrostatic interaction is constructed for magnetic resonance imaging (MRI)-guided multi-mode theranostics with chemotherapy/ferroptosis/immunotherapy. The diselenide bond consumes ROS in TME to increase T cells and ICD efficacy, the cleavage of which facilitates PD-L1 antagonist D peptide release to block immune checkpoint. After intracellular internalization, Fe2O3 nanoparticle is released in the acidic endosome for MRI simultaneously with lipid peroxides generation for tumor ferroptosis. Doxorubicin is cleaved from polymers in the condition of high intracellular GSH level accompanied by tumor ICD, which simultaneously potentiates ferroptosis by NADPH oxidase mediated H2O2 self-generation. In vivo results indicate that the nanoplatform strengthens tumor ICD, induces cytotoxic T lymphocytes proliferation, inhibits 4T1 tumor regression and metastasis, and prolongs survival median. In all, a new strategy is proposed in strengthening ICD and T cells activity cascade with ferroptosis as well as immune checkpoint blockade for effective tumor immunotherapy.


Assuntos
Ferroptose , Peróxido de Hidrogênio , Imunoterapia , Pró-Fármacos , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Ferroptose/efeitos dos fármacos , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Imunoterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética/métodos , Polímeros/química , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Nanopartículas/química , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Feminino , Glutationa/metabolismo , Glutationa/química , Nanomedicina Teranóstica/métodos
7.
Sci Total Environ ; 915: 170105, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38232834

RESUMO

BACKGROUND: Violent conflict is a formidable global challenge, with long-lasting impacts on individual health and society security. There has been compelling evidence that heat can increase aggression intention on the individual level. However, little is known about the short-term relationship between ambient temperature and collective violent conflicts, especially in less developed regions. METHOD: We conducted a time-stratified case-crossover study combined with the distributed lag nonlinear model (DLNM) among 247,773 violent conflicts from 29 countries or regions in the Greater Middle East, between 1997 and 2021. Potential modification effects of economic status and climate conditions were explored by stratified analyses. Negative control and sensitivity analyses were also performed to test the robustness of our model. RESULTS: We observed significant associations between higher temperature and the onset of five categories of violent conflicts. The effects generally occurred within the first several days after exposure. The incidence risks of battles, violence against civilians, explosions/remote violence, protests and riots were 1.60 [95 % confidence interval (CI): 1.31-1.95], 1.82 (95 % CI: 1.37-2.42), 1.24 (95 % CI: 1.08-1.41), 1.16 (95 % CI: 1.09-1.24) and 1.54 (95 % CI: 1.22-1.95) when comparing extreme high temperatures to minimum-risk temperatures. The associations were generally more prominent in areas with lower economic levels and associations in regions of the continental climate are also stronger. CONCLUSIONS: Our finding reveals novel and concrete evidence that short-term high temperature could increase the risk of multiple forms of violent conflict in the Greater Middle East and provides new insights into the potential short-term mechanisms under the heat-collective violence association.


Assuntos
Clima , Temperatura Alta , Temperatura , Estudos Cross-Over , Incidência
8.
Adv Sci (Weinh) ; 11(3): e2306580, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984863

RESUMO

Cancer immunotherapy has become a mainstream cancer treatment over traditional therapeutic modes. Cancer cells can undergo programmed cell death including ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis which are find to have intrinsic relationships with host antitumor immune response. However, direct use of cell death inducers or regulators may bring about severe side effects that can also be rapidly excreted and degraded with low therapeutic efficacy. Nanomaterials are able to carry them for long circulation time, high tumor accumulation and controlled release to achieve satisfactory therapeutic effect. Nowadays, a large number of studies have focused on nanomedicines-based strategies through modulating cell death modalities to potentiate antitumor immunity. Herein, immune cell types and their function are first summarized, and state-of-the-art research progresses in nanomedicines mediated cell death pathways (e.g., ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis) with immune response provocation are highlighted. Subsequently, the conclusion and outlook of potential research focus are discussed.


Assuntos
Apoptose , Nanomedicina , Morte Celular , Piroptose , Autofagia
9.
World J Diabetes ; 14(11): 1621-1631, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38077802

RESUMO

Diabetes mellitus (DM) and obesity have become two of the most prevalent and challenging diseases worldwide, with increasing incidence and serious complications. Recent studies have shown that noncoding RNA (ncRNA) and epigenetic regulation play crucial roles in the pathogenesis of DM complicated by obesity. Identification of the involvement of ncRNA and epigenetic regulation in the pathogenesis of diabetes with obesity has opened new avenues of investigation. Targeting these mechanisms with small molecules or RNA-based therapies may provide a more precise and effective approach to diabetes treatment than traditional therapies. In this review, we discuss the molecular mechanisms of ncRNA and epigenetic regulation and their potential therapeutic targets, and the research prospects for DM complicated with obesity.

10.
Vaccines (Basel) ; 11(9)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37766117

RESUMO

Tumor vaccines have been used to treat cancer. How to efficiently induce tumor-associated antigens (TAAs) secretion with host immune system activation is a key issue in achieving high antitumor immunity. Immunogenic cell death (ICD) is a process in which tumor cells upon an external stimulus change from non-immunogenic to immunogenic, leading to enhanced antitumor immune responses. The immune properties of ICD are damage-associated molecular patterns and TAA secretion, which can further promote dendritic cell maturation and antigen presentation to T cells for adaptive immune response provocation. In this review, we mainly summarize the latest studies focusing on nanotechnology-mediated ICD for effective cancer immunotherapy as well as point out the challenges.

11.
Environ Sci Pollut Res Int ; 30(30): 75752-75767, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37222896

RESUMO

Understanding the relationships between urban expansion and social/environmental features is fundamental to managing watershed and urban expansion. However, such relationships remain unclear, especially across multiple scales of watersheds. Here, we quantified the correlation between urban expansion measures and 255 socioenvironmental indicators across three scales of watersheds running through China (20, 103, and 349 watersheds) during 1992-2016 and analyzed their scaling relations. The results showed that the number of indicators showing a significant correlation with the area and speed of urban expansion increased from 132 and 153 to 234 and 237, respectively, from level 1 to level 3 watersheds. Among these indicators, urban expansion was significantly correlated with indicators of climate and anthropogenic impact. From a large scale (level 1 watershed) to a small scale (level 3 watershed), 104 and 84 socioenvironmental indicators shifted from uncorrelated to significantly correlated with urban expansion area and speed. The constraint line analysis further confirmed that some relationships were nonlinear, which suggested that the drivers and impacts of urban expansion have scaling effects. We argue that it is crucial to consider the scaling effects of urban expansion when we formulate urban or watershed management plans.


Assuntos
Monitoramento Ambiental , Corrida , Monitoramento Ambiental/métodos , China , Meio Social
12.
Theranostics ; 13(6): 1906-1920, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37064869

RESUMO

Rationale: Chemoimmunotherapy is a promising approach in cancer immunotherapy. However, its therapeutic efficacy is restricted by high reactive oxygen species (ROS) levels, an abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME) as well as immune checkpoints for escaping immunosurveillance. Methods: Herein, a new type of TME and reduction dual-responsive polymersomal prodrug (TRPP) nanoplatform was constructed when the D-peptide antagonist (DPPA-1) of programmed death ligand-1 was conjugated onto the surface, and talabostat mesylate (Tab, a fibroblast activation protein inhibitor) was encapsulated in the watery core (DPPA-TRPP/Tab). Doxorubicin (DOX) conjugation in the chain served as an immunogenic cell death (ICD) inducer and hydrophobic part. Results: DPPA-TRPP/Tab reassembled into a micellar structure in vivo with TME modulation by Tab, ROS consumption by 2, 2'-diselanediylbis(ethan-1-ol), immune checkpoint blockade by DPPA-1 and ICD generation by DOX. This resolved the dilemma between a hydrophilic Tab release in the TME for CAF inhibition and intracellular hydrophobic DOX release for ICD via re-assembly in weakly acidic TME with polymersome-micelle transformation. In vivo results indicated that DPPA-TRPP/Tab could improve tumor accumulation, suppress CAF formation, downregulate regulatory T cells and promote T lymphocyte infiltration. In mice, it gave a 60% complete tumor regression ratio and a long-term immune memory response. Conclusion: The study offers potential in tumor eradication via exploiting an "all-in-one" smart polymeric nanoplatform.


Assuntos
Antineoplásicos , Neoplasias , Pró-Fármacos , Animais , Camundongos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Inibidores de Checkpoint Imunológico/farmacologia , Microambiente Tumoral , Espécies Reativas de Oxigênio , Morte Celular Imunogênica , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Imunoterapia/métodos , Doxorrubicina/farmacologia , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Micelas , Linhagem Celular Tumoral
13.
Bioinformatics ; 39(4)2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37010503

RESUMO

MOTIVATION: Therapeutic peptides play an important role in immune regulation. Recently various therapeutic peptides have been used in the field of medical research, and have great potential in the design of therapeutic schedules. Therefore, it is essential to utilize the computational methods to predict the therapeutic peptides. However, the therapeutic peptides cannot be accurately predicted by the existing predictors. Furthermore, chaotic datasets are also an important obstacle of the development of this important field. Therefore, it is still challenging to develop a multi-classification model for identification of therapeutic peptides and their types. RESULTS: In this work, we constructed a general therapeutic peptide dataset. An ensemble-learning method named PreTP-2L was developed for predicting various therapeutic peptide types. PreTP-2L consists of two layers. The first layer predicts whether a peptide sequence belongs to therapeutic peptide, and the second layer predicts if a therapeutic peptide belongs to a particular species. AVAILABILITY AND IMPLEMENTATION: A user-friendly webserver PreTP-2L can be accessed at http://bliulab.net/PreTP-2L.


Assuntos
Aprendizado de Máquina , Peptídeos , Sequência de Aminoácidos
14.
IEEE Trans Pattern Anal Mach Intell ; 45(8): 9611-9626, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37030722

RESUMO

Image defocus is inherent in the physics of image formation caused by the optical aberration of lenses, providing plentiful information on image quality. Unfortunately, existing quality enhancement approaches for compressed images neglect the inherent characteristic of defocus, resulting in inferior performance. This paper finds that in compressed images, significantly defocused regions have better compression quality, and two regions with different defocus values possess diverse texture patterns. These observations motivate our defocus-aware quality enhancement (DAQE) approach. Specifically, we propose a novel dynamic region-based deep learning architecture of the DAQE approach, which considers the regionwise defocus difference of compressed images in two aspects. (1) The DAQE approach employs fewer computational resources to enhance the quality of significantly defocused regions and more resources to enhance the quality of other regions; (2) The DAQE approach learns to separately enhance diverse texture patterns for regions with different defocus values, such that texture-specific enhancement can be achieved. Extensive experiments validate the superiority of our DAQE approach over state-of-the-art approaches in terms of quality enhancement and resource savings.

15.
STAR Protoc ; 4(2): 102177, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37086411

RESUMO

The cross talk between cancer cells and endothelial cells (ECs) within the tumor microenvironment plays a critical role in tumor progression, recurrence, and cancer stemness. Here, we present a protocol containing two in vitro approaches to study such interactions. We first describe an indirect co-culture system to study the regulation of stemness markers in cancer cells by secreted factors from ECs. We then detail a direct co-culture system to study juxtracrine communications between the cell types. For complete details on the use and execution of this protocol, please refer to Sewell-Loftin et al.1 and Guo et al.2.

17.
Small ; 19(23): e2206091, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36855335

RESUMO

Bulk nanobubbles fascinate scientists because of their stability over long periods of time and their ability to carry gases, leading to numerous potential applications. Considering the hypoxic tumor microenvironment and the advantages of bulk nanobubbles, lipid-encapsulated oxygen nanobubbles are prepared from free bulk oxygen nanobubbles in this study. The obtained carrier is then modified with a protein fused with the single-chain antibody of human epidermal growth factor receptor 2 (anti-HER2 scFv) and tandem-repeat cytochrome c (anti-HER2 scFv-nCytc) to enhance tumor targeting and induce tumor apoptosis. Copper phthalocyanine is used as the photosensitizer to demonstrate how the oxygen in the nanobubbles affects the efficiency of photodynamic therapy (PDT). The combination of anti-HER2 scFv-nCytc and PDT synergistically improves the therapeutic effect and alleviates hypoxia in tumors in vivo while causing little inflammatory response. Based on the findings, bulk nanobubble water shows promise in the targeted delivery of oxygen and can be combined with antibody therapy to enhance the efficiency of PDT.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Oxigênio/farmacologia , Hipóxia , Apoptose , Lipídeos , Linhagem Celular Tumoral , Microambiente Tumoral
18.
Acta Otolaryngol ; 143(4): 296-300, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36896993

RESUMO

BACKGROUND: There have been few studies to date exploring prognostic outcomes associated with idiopathic sudden sensorineural hearing loss (ISSNHL) in order adults. OBJECTIVE: This investigation was designed to explore the relationship between atherosclerosis-related risk factors and ISSNHL outcomes among older individuals. MATERIAL AND METHODS: In total, 172 older adults diagnosed ISSNHL from 2016 to 2021 were retrospectively evaluated to compare demographic and clinical test results. RESULTS: Relative to healthy controls, ISSNHL patients exhibited significant differences in hypertension incidence and factors related to coagulation. With respect to prognosis, age, onset days, hypertension, the degree of hearing loss, type of hearing curve, fibrinogen and D-dimer levels were significant univariate prognostic factors, whereas multivariate logistic analysis showed that hypertension (p = .005) and D-dimer concentration (p = .000) were related to the treatment outcome of older ISSNHL patients. The area under the curve (AUC) for D-dimer levels was 0.795 (95% CI: 0.724-0.866). When using a D-dimer cut-off threshold value of 107.5 ng/mL, the sensitivity and specificity values of 77.0% and 76.7%. CONCLUSIONS: The present results indicate that hypertension incidence and D-dimer levels may be presented as an important prognostic indicator in older affected ISSNHL individuals.


Assuntos
Aterosclerose , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Hipertensão , Humanos , Idoso , Estudos Retrospectivos , Prognóstico , Fatores de Risco , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico
19.
Front Mol Neurosci ; 16: 1133303, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36959871

RESUMO

Background: A link has been shown between patent foramen ovale (PFO) and migraine, particularly migraine with aura. However, it is unknown if PFO might cause migraine by altering cortical excitability and neural network, which may lower the threshold of cortical spreading depression (CSD). This study aims to compare the spectrum power and functional connectivity of the alpha and beta bands of electroencephalography (EEG) across migraine patients with and without PFO. Methods: Thirty-five migraine patients with PFO (PFO +), 35 migraine patients without PFO (PFO -) and 20 PFO patients without migraine (control) were enrolled in this cross-sectional analysis. 19-channel EEG was recorded for all patients under resting state and intermittent photic stimulation. Power spectrum density (PSD) and phase lag index (PLI) of alpha and beta bands were then calculated and compared between the three groups. Results: During photic stimulation, the beta band PSD at the occipital area was substantially higher in PFO + migraine patients compared to PFO-migraine patients (p < 0.05, Bonferroni corrected). Subgroup analysis showed that both migraine with and without aura patients with PFO had increased PSD in the alpha and beta bands at the occipital region during photic stimulation (p < 0.05, Bonferroni corrected). Meanwhile, the beta band PLI during photic stimulation was significantly elevated (adjusted p = 0.008, utilizing the network-based statistic technique) in PFO + group compared to PFO-group. Furthermore, although failed to pass the correction, the beta band power in the occipital area during photic stimulation at 20 Hz on O1 (R = 0.392, p = 0.024) and O2 channel (R = 0.348, p = 0.047) was prone to positively correlated with MIDAS score, and during photic stimulation at 12 Hz on O2 channel (R = 0.396, p = 0.022) and 20 Hz (R = 0.365, p = 0.037) on O1 channel was prone to positively correlated to HIT-6 score in PFO+ migraineurs, whereas no similar correlation was found in the PFO-group patients. Conclusion: The outcomes of this investigation suggested that PFO may change the cortical excitability in the occipital lobe of both migraineurs with and without aura. Meanwhile, the beta band PSD on the occipital area during photic stimulation might be an objective measure of severity in migraineurs with PFO.

20.
IEEE/ACM Trans Comput Biol Bioinform ; 20(2): 1337-1344, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35700248

RESUMO

Therapeutic peptide prediction is critical for drug development and therapeutic therapy. Researchers have developed several computational methods to identify different therapeutic peptide types. However, most computational methods focus on identifying the specific type of therapeutic peptides and fail to accurately predict all types of therapeutic peptides. Moreover, it is still challenging to utilize different properties features to predict the therapeutic peptides. In this study, a novel stacking framework PreTP-Stack is proposed for predicting different types of therapeutic peptide. PreTP-Stack is constructed based on ten different features and four predictors (Random Forest, Linear Discriminant Analysis, XGBoost and Support Vector Machine). Then the proposed method constructs an auto-weighted multi-view learning model as a final meta-classifier to enhance the performance of the basic models. Experimental results showed that the proposed method achieved better or highly comparable performance with the state-of-the-art methods for predicting eight types of therapeutic peptides A user-friendly web-server predictor is available at http://bliulab.net/PreTP-Stack.


Assuntos
Desenvolvimento de Medicamentos , Peptídeos , Análise Discriminante , Algoritmo Florestas Aleatórias , Máquina de Vetores de Suporte
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