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1.
Nat Commun ; 15(1): 3780, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710714

RESUMO

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.


Assuntos
Neovascularização de Coroide , Dependovirus , Terapia Genética , Vetores Genéticos , Epitélio Pigmentado da Retina , Animais , Dependovirus/genética , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Terapia Genética/métodos , Camundongos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/virologia , Neovascularização de Coroide/terapia , Neovascularização de Coroide/genética , Coelhos , Humanos , Técnicas de Transferência de Genes , Degeneração Macular/terapia , Degeneração Macular/genética , Degeneração Macular/patologia , Modelos Animais de Doenças , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Transdução Genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retina/virologia , Masculino , Células HEK293
2.
Aust J Gen Pract ; 53(5): 333-336, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38697068

RESUMO

BACKGROUND: Interstitial lung diseases (ILD) are a heterogenous group of over 200 disorders affecting the pulmonary interstitium. Although there have been advances in knowledge on ILDs in Australia, the characterisation of the health and economic burden of disease remained largely undetermined until recently. OBJECTIVE: The main objective of this review is to provide a synopsis of health and economic burden of ILDs in Australia, based on recently completed research. DISCUSSION: Recent research has demonstrated that idiopathic pulmonary fibrosis (IPF) is the most frequent ILD in Australia. Incidence and prevalence of IPF have demonstrated an increasing trend over the past decades. Mortality has also increased over the past decades, but has shown a slight decreasing trend recently, since the introduction of antifibrotic medication. Health-related quality of life is poor in patients with IPF, and care is estimated to cost approximately AU$299 million per year in Australia. Early diagnosis and referral to tertiary care is crucial for favourable outcomes, and general practitioners are considerably important to this as the first interface to identify patients at risk and detect early symptoms of ILDs.


Assuntos
Efeitos Psicossociais da Doença , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/economia , Doenças Pulmonares Intersticiais/terapia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Austrália/epidemiologia , Qualidade de Vida/psicologia , Prevalência , Adulto , Fibrose Pulmonar Idiopática/economia , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/terapia , Incidência
3.
Fitoterapia ; 176: 105985, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705541

RESUMO

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

4.
Sci Rep ; 14(1): 10509, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714697

RESUMO

Chronic non-communicable diseases (CNCDs) pose a significant public health challenge. Addressing this issue, there has been a notable breakthrough in the prevention and mitigation of NCDs through the use of antioxidants and anti-inflammatory agents. In this study, we aim to explore the effectiveness of Eupatorium adenophora Spreng leaves (EASL) as an antioxidant and anti-inflammatory agent, and its potential applications. To construct a cellular model of oxidative damage and inflammation, Caco-2 cells were treated with tert-butyl hydroperoxide (t-BHP). The biocompatibility of EASL-AE with Caco-2 cells was assessed using the MTT assay, while compatibility was further verified by measuring LDH release and the protective effect against oxidative damage was also assessed using the MTT assay. Additionally, we measured intracellular oxidative stress indicators such as ROS and 8-OHdG, as well as inflammatory pathway signalling protein NFκB and inflammatory factors TNF-α and IL-1ß using ELISA, to evaluate the antioxidant and anti-inflammatory capacity of EASL-AE. The scavenging capacity of EASL-AE against free radicals was determined through the DPPH Assay and ABTS Assay. Furthermore, we measured the total phenolic, total flavonoid, and total polysaccharide contents using common chemical methods. The chemical composition of EASL-AE was analyzed using the LC-MS/MS technique. Our findings demonstrate that EASL-AE is biocompatible with Caco-2 cells and non-toxic at experimental levels. Moreover, EASL-AE exhibits a significant protective effect on Caco-2 cells subjected to oxidative damage. The antioxidant effect of EASL-AE involves the scavenging of intracellular ROS, while its anti-inflammatory effect is achieved by down-regulation of the NFκB pathway. Which in turn reduces the release of inflammatory factors TNF-α and IL-1ß. Through LC-MS/MS analysis, we identified 222 compounds in EASL-AE, among which gentianic acid, procaine and L-tyrosine were the compounds with high antioxidant capacity and may be the effective constituent for EASL-AE with antioxidant activity. These results suggest that EASL-AE is a natural and high-quality antioxidant and anti-inflammatory biomaterial that warrants further investigation. It holds great potential for applications in healthcare and other related fields.


Assuntos
Anti-Inflamatórios , Antioxidantes , Estresse Oxidativo , Extratos Vegetais , Folhas de Planta , terc-Butil Hidroperóxido , Humanos , Células CACO-2 , terc-Butil Hidroperóxido/farmacologia , Folhas de Planta/química , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Estresse Oxidativo/efeitos dos fármacos , Eupatorium/química , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo
5.
Int J Surg ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781043

RESUMO

BACKGROUND: The aim of this study is to assess the diagnostic accuracy of intraoperative frozen section (FS) in determining the pathological subtypes among patients diagnosed with cT1N0M0 invasive lung adenocarcinoma. MATERIALS AND METHODS: This was a prospective, multi-center (7 centers in China) clinical trial of Eastern Cooperative Thoracic Oncology Projects (ECTOP-1015). Patients with cT1N0M0 invasive lung adenocarcinoma were enrolled in the study. Pathological images obtained from FS and final pathology (FP) were reviewed by at least two pathologists. The primary endpoint was the concordance between FS and FP diagnoses. The inter-observer agreement for identifying pathological subtypes on FS was evaluated among three pathologists. RESULTS: A total of 935 patients were enrolled. The best sensitivity of diagnosing the predominant subtype was 78.2% in the evaluation of acinar pattern. Presence of acinar pattern diagnosed by FS was an independent factor for the concordance between FS and FP (P=0.007, 95% CI: 2.332-4.736). Patients with tumor size >2 cm measured by pathology showed a better concordance rate for the predominant subtype (81.6% vs 74.6%, P=0.023). The presence of radiological ground glass opacity (GGO) component did not affect the diagnosis accuracy of FS for predominant subtype (concordance rate: 76.4% vs 75.2%, P=0.687). Patients with GGO component showed better accuracy of the identification in the presence of LPA (82.1% vs 71.0%, P= 0.026). Substantial agreement between the FS diagnosis from 3 pathologists for the predominant pathological pattern was revealed with κ = 0.846. CONCLUSIONS: This is the largest prospective trial evaluating FS diagnosing pathological subtype in cT1N0M0 invasive lung adenocarcinoma. A favorable concordance in the assessment of the pathological subtypes between FS and FP was observed, indicating the feasibility of utilizing accurate intraoperative pathological diagnoses from FS in guiding surgical strategies. And combination of radiology could improve the precision of FS.

6.
Biol Proced Online ; 26(1): 10, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632527

RESUMO

BACKGROUND: Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. METHODS: This retrospective study analyzed 337 ESCC resection specimens from 2020-2021 at the Pudong-Branch (Cohort 1) and 114 from 2021-2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. RESULTS: The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. CONCLUSION: This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

7.
Front Microbiol ; 15: 1323499, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444803

RESUMO

In many oceanic regions, anthropogenic warming will coincide with iron (Fe) limitation. Interactive effects between warming and Fe limitation on phytoplankton physiology and biochemical function are likely, as temperature and Fe availability affect many of the same essential cellular pathways. However, we lack a clear understanding of how globally significant phytoplankton such as the picocyanobacteria Synechococcus will respond to these co-occurring stressors, and what underlying molecular mechanisms will drive this response. Moreover, ecotype-specific adaptations can lead to nuanced differences in responses between strains. In this study, Synechococcus isolates YX04-1 (oceanic) and XM-24 (coastal) from the South China Sea were acclimated to Fe limitation at two temperatures, and their physiological and proteomic responses were compared. Both strains exhibited reduced growth due to warming and Fe limitation. However, coastal XM-24 maintained relatively higher growth rates in response to warming under replete Fe, while its growth was notably more compromised under Fe limitation at both temperatures compared with YX04-1. In response to concurrent heat and Fe stress, oceanic YX04-1 was better able to adjust its photosynthetic proteins and minimize the generation of reactive oxygen species while reducing proteome Fe demand. Its intricate proteomic response likely enabled oceanic YX04-1 to mitigate some of the negative impact of warming on its growth during Fe limitation. Our study highlights how ecologically-shaped adaptations in Synechococcus strains even from proximate oceanic regions can lead to differing physiological and proteomic responses to these climate stressors.

8.
MAGMA ; 37(2): 241-256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38315352

RESUMO

OBJECTIVES: CT and MR are often needed to determine the location and extent of brain lesions collectively to improve diagnosis. However, patients with acute brain diseases cannot complete the MRI examination within a short time. The aim of the study is to devise a cross-device and cross-modal medical image synthesis (MIS) method Cross2SynNet for synthesizing routine brain MRI sequences of T1WI, T2WI, FLAIR, and DWI from CT with stroke and brain tumors. MATERIALS AND METHODS: For the retrospective study, the participants covered four different diseases of cerebral ischemic stroke (CIS-cohort), cerebral hemorrhage (CH-cohort), meningioma (M-cohort), glioma (G-cohort). The MIS model Cross2SynNet was established on the basic architecture of conditional generative adversarial network (CGAN), of which, the fully convolutional Transformer (FCT) module was adopted into generator to capture the short- and long-range dependencies between healthy and pathological tissues, and the edge loss function was to minimize the difference in gradient magnitude between synthetic image and ground truth. Three metrics of mean square error (MSE), peak signal-to-noise ratio (PSNR), and structure similarity index measure (SSIM) were used for evaluation. RESULTS: A total of 230 participants (mean patient age, 59.77 years ± 13.63 [standard deviation]; 163 men [71%] and 67 women [29%]) were included, including CIS-cohort (95 participants between Dec 2019 and Feb 2022), CH-cohort (69 participants between Jan 2020 and Dec 2021), M-cohort (40 participants between Sep 2018 and Dec 2021), and G-cohort (26 participants between Sep 2019 and Dec 2021). The Cross2SynNet achieved averaged values of MSE = 0.008, PSNR = 21.728, and SSIM = 0.758 when synthesizing MRIs from CT, outperforming the CycleGAN, pix2pix, RegGAN, Pix2PixHD, and ResViT. The Cross2SynNet could synthesize the brain lesion on pseudo DWI even if the CT image did not exhibit clear signal in the acute ischemic stroke patients. CONCLUSIONS: Cross2SynNet could achieve routine brain MRI synthesis of T1WI, T2WI, FLAIR, and DWI from CT with promising performance given the brain lesion of stroke and brain tumor.


Assuntos
Neoplasias Encefálicas , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Processamento de Imagem Assistida por Computador
10.
Int Wound J ; 21(2): e14774, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361180

RESUMO

This meta-analysis aims to comprehensively assess the impact of laparoscopic radical prostatectomy (LRP) on wound infection in patients with prostate cancer (PCa). A systematic search was conducted, from database inception to November 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) comparing LRP with open radical prostatectomy (ORP) in the treatment of PCa. Two researchers independently screened the literature, extracted data and conducted quality assessments based on pre-defined inclusion and exclusion criteria. Stata 17.0 software was employed for data analysis. Overall, 15 RCTs involving 1458 PCa patients were included. The analysis revealed the incidence of wound infection (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.16-0.51, p < 0.001) and complications (OR = 0.27, 95% CI = 0.20-0.37, p < 0.001) was significantly lower in the LRP group compared to the ORP group. This study demonstrates that LRP in PCa patients can effectively reduce the incidence of wound infections and complications, indicating significant therapeutic efficacy and justifying its broader clinical application.


Assuntos
Laparoscopia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Infecção dos Ferimentos , Masculino , Humanos , Neoplasias da Próstata/cirurgia , Prostatectomia/efeitos adversos , Laparoscopia/efeitos adversos , Infecção dos Ferimentos/cirurgia
11.
Cell Chem Biol ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38309277

RESUMO

The lysosome-targeting chimera (LYTAC) approach has shown promise for the targeted degradation of secreted and membrane proteins via lysosomes. However, there have been challenges in design, development, and targeting. Here, we have designed a genetically engineered transferrin receptor (TfR)-mediated lysosome-targeting chimera (TfR-LYTAC) that is efficiently internalized via TfR-mediate endocytosis and targets PD-L1 for lysosomal degradation in cultured cells but not in vivo due to short half-life and poor tumor targeting. A delivery platform was developed by fusing TfR-LYTAC to the surface of bacterial outer membrane vesicles (OMVs). The engineered OMV-LYTAC combines PD-1/PD-L1 pathway inhibition with LYTAC and immune activation by bacterial OMVs. OMV-LYTAC significantly reduced tumor growth in vivo. We have provided a modular and simple genetic strategy for lysosomal degradation as well as a delivery platform for in vivo tumor targeting. The study paves the way for the targeting and degradation of extracellular proteins using the TfR-LYTAC system.

12.
Cell Rep Med ; 5(1): 101358, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38183982

RESUMO

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Proteogenômica , Humanos , Neoplasias Pulmonares/patologia , Proteômica , Células Endoteliais/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/genética
13.
Plast Reconstr Surg ; 153(1): 44e-53e, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36988680

RESUMO

BACKGROUND: Bulbar conjunctival prolapse is one of the complications of conjoint fascial sheath (CFS) suspension and has a negative impact on surgical results. To explore the prevention methods of this complication, the authors compared the incidence of it between the below-conjunctiva fornix-bulbar conjunctiva-Tenon capsule (CBT) approach and the above-CBT approach to dissecting CFS in CFS suspension and shared their experience in the treatment of bulbar conjunctival prolapse. METHODS: From January of 2020 to August of 2021, 81 patients with severe congenital ptosis who underwent CFS suspension were enrolled and divided into two groups. Forty-five patients' (group A) CFS was dissected by means of the below-CBT approach and 36 patients' (group B) CFS was dissected by means of the above-CBT approach. Data regarding the incidence and outcomes of bulbar conjunctival prolapse and the postoperative condition were collected and analyzed. RESULTS: The incidence of bulbar conjunctival prolapse was 24.44% in group A and 2.78% in group B. Of the 12 bulbar conjunctival prolapse patients, seven patients' conditions improved after conservative treatment, and five did not. All of them underwent bulbar conjunctiva resection within 1 year and were cured. No recurrent prolapse was observed within 3 months postoperatively. At the last follow-up, the mean marginal reflex distance 1 and palpebral fissure height were 4.09 ± 0.19 mm and 9.85 ± 0.62 mm, respectively. There were no complications except lagophthalmos (16 eyelids), asymmetric eyelid contour (one patient), and trichiasis (two eyelids). CONCLUSIONS: The incidence of bulbar conjunctival prolapse decreased significantly by dissecting CFS by means of the above-CBT approach. For patients with bulbar conjunctival prolapse after CFS suspension, bulbar conjunctiva resection could provide satisfactory results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Blefaroptose , Cápsula de Tenon , Humanos , Túnica Conjuntiva/cirurgia , Pálpebras/cirurgia , Blefaroptose/cirurgia , Prolapso
14.
Int J Biol Macromol ; 257(Pt 2): 128670, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070794

RESUMO

In this study, a novel nano-drug delivery system (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Myricaria germanica polysaccharide (MGP) was developed to enhance immune responses. At a MGP to CS Au ratio of 5:1, CS-Au-MGP NPs had a loading capacity of 78.27 %. The structure of CS-Au-MGP NPs were characterized by Transmission electron microscope, TEM-energy dispersive spectroscopy mapping, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometer, particle size and zeta-potential distribution analysis. Under weakly acidic conditions, in vitro CS-Au-MGP NPs release was most effective. In vivo showed that co-immunization with CS-Au-MGP NPs and PCV2 significantly increased the organ index of the thymus, spleen, and liver in mice. Additionally, CS-Au-MGP NPs significantly increased the levels of IgG, IgG1, and IgG2a antibodies, as well as IFN-γ and IL-6 levels. Furthermore, the CS-Au-MGP NPs promoted proliferation of spleen T and B lymphocytes, increased the number of CD3+, CD4+, and CD8+ cells, and increased the CD4+/CD8+ T cell ratio. Meanwhile, CS-Au-MGP NPs remarkably TLR2/IRAK4 pathway activation and mRNA levels of cytokines (IFN-γ and IL-6). These results indicated that CS-Au-MGP NPs could enhance the immune activity, and it could be potentially used as an MGP delivery system for the induction of strong immune responses.


Assuntos
Quitosana , Nanopartículas Metálicas , Nanopartículas , Camundongos , Animais , Quitosana/química , Ouro/química , Interleucina-6 , Nanopartículas/química , Polissacarídeos/farmacologia , Imunidade
15.
FEBS Open Bio ; 14(1): 127-137, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37964494

RESUMO

Sorafenib resistance greatly restricts its clinical application in patients with hepatocellular carcinoma (HCC). Numerous studies have reported that ID1 exerts a crucial effect in cancer initiation and development. Our previous research revealed an inhibitory role of ID1 in sorafenib resistance. However, the upstream regulatory mechanism of ID1 expression is unclear. Here, we discovered that ID1 expression is negatively correlated with promoter methylation, which is regulated by DNMT3B. Knockdown of DNMT3B significantly inhibited ID1 methylation status and resulted in an increase of ID1 expression. The demethylating agent 5-aza-2'-deoxycytidine (5-aza) remarkably upregulated ID1 expression. The combination of 5-aza with sorafenib showed a synergistic effect on the inhibition of cell viability.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Azacitidina/farmacologia , Metilação , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo
16.
Pest Manag Sci ; 80(3): 1533-1546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37964702

RESUMO

BACKGROUND: Spodoptera frugiperda, a global agricultural pest, can be effectively controlled through the sterile insect technique. However, exposure to low-dose radiation below the sterilization threshold may induce hormetic effects. Here, the biphasic aspects of the fertile progeny population of S. frugiperda were analyzed using an age-stage, two-sex life table after dosing male and female pupae with 10-350 Gy gamma radiation. RESULTS: The parental sterilizing dose for 6-day-old female and male pupae was 200 and 350 Gy, respectively. The total longevity, pre-adult survival rate, net reproduction rate, and intrinsic growth rate of the offspring population increased with decreasing radiation doses from 250 to 10 Gy. Offspring population of parents treated with low doses of 10-100 Gy showed better life table parameters compared to non-irradiated controls. Females and males fecundity irradiated with 10, 50, and 100 Gy and 10 Gy, respectively, exceeded controls, producing 2339.4, 2726.4, 2311, and 2369 eggs, as opposed to 1802.9 eggs produced by the controls. Males irradiated with 10 Gy displayed the highest intrinsic rates of increase and net reproduction rate, at 0.1709 and 682.3, respectively. Projections from the survival rate and fecundity indicated that female and male S. frugiperda populations after 10 Gy irradiation may grow considerably faster than the controls. CONCLUSION: This study explores the hormetic effects of low-dose radiation on S. frugiperda through life table analysis, while providing enhancements for utilizing substerilizing gamma dose in a modified F1 sterility technique. © 2023 Society of Chemical Industry.


Assuntos
Infertilidade , Mariposas , Animais , Masculino , Feminino , Spodoptera , Tábuas de Vida , Fertilidade
17.
Nat Nanotechnol ; 19(1): 124-130, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37696994

RESUMO

In vivo quantitative assessment of oxyhaemoglobin saturation (sO2) status in tumour-associated vessels could provide insights into cancer metabolism and behaviour. Here we develop a non-invasive in vivo sO2 imaging technique to visualize the sO2 levels of healthy and tumour tissue based on photoluminescence bioimaging in the near-infrared IIb (NIR-IIb; 1,500-1,700 nm) window. Real-time dynamic sO2 imaging with a high frame rate (33 Hz) reveals the cerebral arteries and veins through intact mouse scalp/skull, and this imaging is consistent with the haemodynamic analysis results. Utilizing our non-invasive sO2 imaging, the tumour-associated-vessel sO2 levels of various cancer models are evaluated. A positive correlation between the tumour-associated-vessel sO2 levels and the basal oxygen consumption rate of corresponding cancer cells at the early stages of tumorigenesis suggests that cancer cells modulate the tumour metabolic microenvironment. We also find that a positive therapeutic response to the checkpoint blockade cancer immunotherapy could lead to a dramatic decrease of the tumour-associated-vessel sO2 levels. Two-plex dynamic NIR-IIb imaging can be used to simultaneously observe tumour-vessel sO2 and PD-L1, allowing a more accurate prediction of immunotherapy response.


Assuntos
Neoplasias , Oxiemoglobinas , Animais , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Diagnóstico por Imagem , Imunoterapia , Microambiente Tumoral
18.
Aesthetic Plast Surg ; 48(3): 333-340, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37697086

RESUMO

BACKGROUND: Poor Bell's phenomenon is often considered a relative contraindication for ptosis surgery, as it increases the risk of corneal exposure and dry eye symptoms after surgery. However, the Bell's phenomenon may vary in different individuals and sleep stages, making it inaccurate to predict the position of the eye during sleep based on awake examination. This study aimed to investigate the role of Bell's phenomenon in ptosis surgery and the management of nocturnal lagophthalmos. METHODS: We conducted a retrospective case series of 23 patients with ptosis and poor Bell's phenomenon who underwent different surgical techniques at Xijing Hospital from April 2020 to June 2021. We assessed Bell's phenomenon at different stages of sleep and collected data on ptosis degree, surgical approach, lagophthalmos, complications, and outcomes. RESULTS: Of the total 23 patients originally considered for study, 9 with frontalis muscle advancement technique, 8 with conjoint fascial sheath suspension, 4 with levator resection technique, and 2 with levator aponeurosis plication technique. All patients achieved satisfactory correction of ptosis. One patient had prolonged lagophthalmos and underwent reoperation to lower the eyelid height. Other complications were minor and resolved with conservative treatment. CONCLUSION: We conclude that poor Bell's phenomenon is not a relative contraindication for ptosis surgery. Nocturnal lagophthalmos should be monitored after ptosis surgery regardless of the Bell's phenomenon results. Tape eyelid closure can be an effective solution to protect the corneal surface during nocturnal lagophthalmos. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Blefaroplastia , Blefaroptose , Lagoftalmia , Humanos , Estudos Retrospectivos , Músculos Oculomotores/cirurgia , Blefaroptose/cirurgia , Blefaroplastia/métodos , Pálpebras/cirurgia
19.
Ann Plast Surg ; 92(1): 12-16, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38117043

RESUMO

BACKGROUND: Lagophthalmos, a common complication after blepharoptosis correction, has plagued oculoplastic surgeons. The goal of this study was to investigate the effect of tape eyelid closure on reducing the occurrence of lagophthalmos after blepharoptosis correction. METHODS: From April 2020 to June 2021, a total of 112 patients with severe congenital ptosis received corrective surgery at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University. Of these, 48 underwent frontalis muscle advancement technique and 64 underwent conjoint fascial sheath suspension. Preoperative data collected included demographics, levator function, Bell's phenomenon, and marginal reflex distance 1 (MRD1). Postoperative data included surgery type, MRD1, eyelid closure function, aesthetic outcomes (including eyelid contour, eyelid symmetry, and eyelid crease), keratitis, and other complications. RESULTS: Frontalis muscle advancement technique group: the median of safe eye closure time was 7.3 months (positive Bell's phenomenon; interquartile range [IQR], 3.8-10.8 months) and 13.9 months (poor Bell's phenomenon; IQR, 11.6-16.1 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.52 ± 0.82 vs 3.85 ± 0.58 mm, P < 0.05). Conjoint fascial sheath suspension group: the median of safe eye closure time was 5.7 months (positive Bell's phenomenon; IQR, 2.9-8.5 months) and 12.4 months (poor Bell's phenomenon; IQR, 8.1-16.7 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.02 ± 0.91 vs 4.15 ± 1.03 mm, P < 0.05). All patients/guardians were satisfied with the aesthetic outcomes. CONCLUSIONS: Tape tarsorrhaphy is a safe, easy-to-learn method for treating lagophthalmos with a good aesthetic outcome.


Assuntos
Blefaroplastia , Blefaroptose , Lagoftalmia , Humanos , Blefaroptose/cirurgia , Blefaroptose/congênito , Músculos Oculomotores/cirurgia , Pálpebras/cirurgia , Blefaroplastia/métodos , Estudos Retrospectivos , Resultado do Tratamento
20.
Ann Plast Surg ; 92(1): 55-59, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38117045

RESUMO

BACKGROUND: Severe congenital ptosis is a common ocular deformity in pediatric patients that can significantly impact visual development and aesthetic appearance, leading to negative psychosocial outcomes. The frontalis muscle advancement technique is a well-established surgical treatment for severe congenital ptosis. Aesthetic changes of the brow-eye continuum often plays an important role in ptosis surgery. METHODS: We conducted a single-center retrospective case series study of patients with severe congenital ptosis who underwent the frontalis muscle advancement technique at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University between April 2020 and June 2021. The study aimed to evaluate the aesthetic changes of the eyebrow-eyelid continuum after surgery. The main outcome measurements included marginal reflex distance 1, palpebral fissure height, eyebrow position, upper eyelid to lower eyebrow distance, lower eyelid to upper eyebrow distance, and nasal base to lower eyelid distance. RESULTS: The study included 48 patients (66 eyelids), with 30 unilateral and 18 bilateral patients. Our analysis found that eyebrow height decreased by an average of 4.8% postoperatively relative to preoperatively in all patients. CONCLUSIONS: The frontalis muscle advancement technique has demonstrated effectiveness in achieving aesthetically pleasing outcomes in children with severe ptosis. It is crucial to pay careful attention to the brow-eye continuum during the correction process, as its harmony can greatly impact the final result.


Assuntos
Blefaroplastia , Blefaroptose , Humanos , Criança , Blefaroplastia/métodos , Estudos Retrospectivos , Blefaroptose/cirurgia , Blefaroptose/congênito , Estética , Músculos/cirurgia , Músculos Oculomotores/cirurgia
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