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1.
Artigo em Inglês | MEDLINE | ID: mdl-38847893

RESUMO

PURPOSE: To evaluate whether depth of focus after the implantation of extended depth of focus (EDoF) intraocular lenses (IOLs) correlates with pupillary size. METHODS: This retrospective case series study evaluated eyes undergoing cataract surgery with implantation of EDoF IOLs. At least one month postoperatively, the depth of focus (DoF) was measured to determine the correlation with pupillary size, age, anterior chamber depth (ACD), axial length (AXL), and corneal spherical aberrations (SA). RESULTS: The study evaluated 64 eyes of 49 patients. The mean depth of focus was 2.67 diopters (D). The mean preoperative photopic pupil size was 3.36 mm. A significant negative association was found between preoperative photopic pupil size and depth of focus (r = 0.30, Pearson's correlation coefficient) and between preoperative mesopic pupil size and depth of focus (r = 0.274, Pearson's correlation coefficient).

2.
Clin Cosmet Investig Dermatol ; 17: 847-851, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633469

RESUMO

We report a case of rash in a 35-year-old female presenting with erythematous papules and infiltrative plaques on the nose and upper jaw resembling rosacea. The patient had been experiencing these symptoms for one year. A pathological biopsy revealed an inflammatory infiltrate consisting of dense perivascular lymphocytes surrounding hair follicles and sweat glands in the dermis. Immunohistochemistry demonstrated a predominance of CD4+ T cells compared to CD8+ T cells. Based on the clinical manifestations, histopathology, and immunohistochemistry, the patient was diagnosed with Jessner's Lymphocytic infiltration of the skin (JLIS). The patient was treated with oral Minocycline, 100mg twice daily. After 4 weeks, the dosage was reduced by half and the treatment continued for 2 months, resulting in complete resolution of the rash. The clinical presentation resembled rosacea, and this particular manifestation of JLIS has not been previously reported. Treatment with minocycline yielded satisfactory efficacy, and no recurrence has been observed for 5 year.

3.
Mol Ther Nucleic Acids ; 35(1): 102127, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38352860

RESUMO

RNA editing plays an extensive role in the initiation and progression of cancer. However, the overall profile and molecular functions of RNA editing in different ovarian cancer subtypes have not been fully characterized and elucidated. Here, we conducted a study on RNA editing in four cohorts of ovarian cancer subtypes through large-scale parallel reporting and bioinformatics analysis. Our findings revealed that RNA editing patterns exhibit subtype-specific characteristics within cancer subtypes. The expression pattern of ADAR and the number of differential editing sites varied under different conditions. CCOC and EOC exhibited significant editing deficiency, whereas HGSC and MOC displayed significant editing excess. The sites within the turquoise module of the coedited network also revealed their correlation with ovarian cancer. In addition, we identified an average of over 40,000 cis-edQTLs in the four subtypes. Finally, we explored the association between RNA editing and drug response, uncovering several potentially effective editing-drug pairs (EDP) and suggesting the conceivable utility of RNA editing sites as therapeutic targets for cancer treatment. Overall, our comprehensive study has identified and characterized RNA editing events in various subtypes of ovarian cancer, providing a new perspective for ovarian cancer research and facilitating the development of medical interventions and treatments.

4.
J Photochem Photobiol B ; 252: 112851, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38306801

RESUMO

Curcumin (CUR), a natural compound extracted from turmeric, has shown potential as a photosensitizer in photodynamic therapy (PDT). The aim of this work was to enhance the efficacy of CUR by modifying it using titanium dioxide (TiO2) nanoparticles and a cationic polymer called Sofast to create a nanocomposite TiO2-CUR-Sofast (TCS). Compared to unmodified CUR, TCS exhibited a broadening toward longer wavelength in the absorption wavelength within the 400-550 nm range, leading to improved CUR absorption. Cellular uptake efficiency of TCS was also enhanced, and it demonstrated nearly 4.7-fold higher reactive oxygen species (ROS) generation than CUR. Furthermore, TCS displayed the ability to attach to the cell membrane and enter cells within a 30-min incubation period. Upon irradiation, TCS exhibited remarkable cytotoxicity, resulting in a significant reduction in the viability of various cancer cells. Autofluorescence lifetime imaging of intracellular reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) enzymes indicated that cancer cells treated with TCS and irradiation undergo a metabolic pathway shift from oxidative phosphorylation to glycolysis. These findings highlight the potential of TCS as an effective PDT agent for cancer treatment.


Assuntos
Curcumina , Nanopartículas , Fotoquimioterapia , Curcumina/farmacologia , Fotoquimioterapia/métodos , Polímeros , Fármacos Fotossensibilizantes/farmacologia
5.
Arch Med Sci ; 20(1): 267-279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414469

RESUMO

Introduction: The ITGB6 gene encoding a protein that can regulate the integrin αvß6 heterodimer protein expression in different status was shown to play an important role in multiple human cancers, such as brain cancer, colon cancer and oral cancer, and is related to clinical progression. This study aims to explore the function and the mechanism of the ITGB6 gene or protein in pancreatic cancer. Material and methods: We examined the expression of ITGB6 in pancreatic cancer using immunohistochemistry and analyzed the relationship between the expression of ITGB6 and the clinicopathologic features in pancreatic cancer patients. In addition, a bioinformatic method was used to analyze the ITGB6 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the correlation between high KIF23 expression and prognosis in pancreatic cancer patients. Moreover, colony formation assay, MTT assay, cell scratch, cell invasion and western blot assays in vitro and a xenograft mouse model in vivo were performed to analyze the effect of KIF23 on proliferation and invasion of pancreatic cancer cells. Results: Increased expression of ITGB6 was significantly correlated with poor clinical outcome in both our clinical data and TCGA data of pancreatic cancer. Furthermore, functional assays revealed that ITGB6 knockdown in vivo and in vitro might inhibit cancer cell proliferation and the ability of invasion or migration. Conclusions: Our data suggest that ITGB6 is associated with pancreatic cancer malignant progression. Hence, ITGB6 may serve as a potential target of pancreatic cancer for future research, and further study is needed.

6.
Clin Oral Implants Res ; 35(3): 350-357, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38174662

RESUMO

OBJECTIVES: To compare the accuracy of immediate implant placement of cylindrical implants (CI) and tapered implants (TI) of different lengths using a robotic dental implant system. MATERIALS AND METHODS: CI and TI of three lengths (8, 10, and 12 mm) each were digitally planned and placed in a three-dimensional printed extraction socket model under robotic guidance. There were six groups with three samples in each group, resulting in a total of 18 samples. Implant angular deviation, platform point deviation (total, lateral, depth), and implant apical point deviation (total, lateral, depth) were recorded and compared between the different groups. RESULTS: The angular deviations for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 1.32° ± 0.19°, 1.03° ± 0.56°, 1.31° ± 0.38°, 1.27° ± 0.64°, 1.10° ± 0.43° and 1.05° ± 0.45°, respectively. The total deviations of platform and apical points for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 0.79 ± 0.18 mm, 0.77 ± 0.33 mm; 0.64 ± 0.21 mm, 0.55 ± 0.17 mm; 0.64 ± 0.37 mm, 0.65 ± 0.34 mm; 0.68 ± 0.26 mm, 0.71 ± 0.20 mm; 0.70 ± 0.12 mm, 0.66 ± 0.23 mm; and 0.71 ± 0.15 mm, 0.77 ± 0.29 mm, respectively, and had no significant differences. CONCLUSIONS: Within the limitation of this study, acceptable accuracy can be achieved for both TI and CI using robotic systems. Our study demonstrated that the implant shape and length did not affect the accuracy of immediate implant placement under robotic guidance in vitro. However, further trials are required to confirm their efficacy in clinical practice.


Assuntos
Implantes Dentários , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgia Assistida por Computador , Implantação Dentária Endóssea/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Desenho Assistido por Computador , Imageamento Tridimensional/métodos
7.
J Thorac Oncol ; 19(4): 613-625, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38070598

RESUMO

INTRODUCTION: Variable partners and breakpoints have been reported in patients with ROS1-rearranged NSCLC. Here, we investigated the association of fusion partners and breakpoints with crizotinib efficacy in NSCLCs with common ROS1 fusions. METHODS: DNA and RNA next-generation sequencing (NGS) and immunohistochemistry were performed to characterize ROS1 fusions. RESULTS: Using DNA NGS, we identified ROS1 fusions in 210 cases, comprising 171 common (CD74/EZR/TPM3/SDC4/SLC34A2-ROS1) and 39 uncommon (variants identified in <5%) ROS1 fusion cases. DNA NGS detected variable ROS1 genomic breakpoints in common ROS1 fusions, whereas RNA NGS found ROS1 breakpoints mainly occurring in exons 32, 34 and 35, resulting in long (exon 32) and short (exon 34 or 35) ROS1 fusions. ROS1 immunohistochemistry revealed that membranous and cytoplasmic staining was predominant in long ROS1 fusions, whereas cytoplasmic staining was predominant in short ROS1 fusions (p = 0.006). For patients who received first-line crizotinib, median progression-free survival (mPFS) was lower in patients with long ROS1 fusions than those with short ROS1 fusions (8.0 versus 24.0 mo, p = 0.006). Moreover, mPFS for patients with and without TP53 mutations was 8.0 and 19.0 months, respectively (p = 0.159); mPFS for patients with and without BIM deletion polymorphism was 5.0 and 22.0 months, respectively (p = 0.003). When analyzing together with fusion partners, patients with long CD74/SLC34A2-ROS1 fusions were found to have shorter PFS than those with other ROS1, regardless of the presence or absence of TP53 mutations (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: Long CD74/SLC34A2-ROS1 fusions, which retain transmembrane regions in ROS1 and fusion partners, are associated with poor response to crizotinib independent of TP53 mutations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Antígenos de Histocompatibilidade Classe II , Neoplasias Pulmonares , Proteínas de Fusão Oncogênica , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , DNA , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Proteínas de Fusão Oncogênica/genética , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/genética , Proteína Supressora de Tumor p53/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Diferenciação de Linfócitos B/genética
8.
J. appl. oral sci ; 32: e20230294, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1558234

RESUMO

Abstract Objective This study aims to develop a compound biomaterial to achieve effective soft tissue regeneration. Methodology Compound hyaluronic acid (CHA) and liquid horizontal-platelet-rich fibrin (H-PRF) were mixed at a ratio of 1:1 to form a CHA-PRF gel. Human gingival fibroblasts (HGFs) were used in this study. The effect of CHA, H-PRF, and the CHA-PRF gel on cell viability was evaluated by CCK-8 assays. Then, the effect of CHA, H-PRF, and the CHA-PRF gel on collagen formation and deposition was evaluated by qRT‒PCR and immunofluorescence analysis. Finally, qRT‒PCR, immunofluorescence analysis, Transwell assays, and scratch wound-healing assays were performed to determine how CHA, H-PRF, and the CHA-PRF gel affect the migration of HGFs. Results The combination of CHA and H-PRF shortened the coagulation time of liquid H-PRF. Compared to the pure CHA and H-PRF group, the CHA-PRF group exhibited the highest cell proliferation at all time points, as shown by the CCK-8 assay. Col1a and FAK were expressed at the highest levels in the CHA-PRF group, as shown by qRT‒PCR. CHA and PRF could stimulate collagen formation and HGF migration, as observed by fluorescence microscopy analysis of COL1 and F-actin and Transwell and scratch healing assays. Conclusion The CHA-PRF group exhibited greater potential to promote soft tissue regeneration by inducing cell proliferation, collagen synthesis, and migration in HGFs than the pure CHA or H-PRF group. CHA-PRF can serve as a great candidate for use alone or in combination with autografts in periodontal or peri-implant soft tissue regeneration.

9.
BMC Ophthalmol ; 23(1): 401, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803306

RESUMO

BACKGROUND: Neovascular age-related macular degeneration (AMD) is responsible for the majority of severe vision loss cases and is mainly caused by choroidal neovascularization (CNV). This condition persists or recurs in a subset of patients and regresses after 5 or more years of anti-vascular endothelial growth factor (VEGF) treatment. The precise mechanisms of CNV continue to be elucidated. According to our previous studies, macrophages play a critical role in CNV. Herein, we aimed to determine the morphological changes in macrophages in CNV to help us understand the dynamic changes. METHODS: Mice were subjected to laser injury to induce CNV, and lesion expansion and macrophage transformation were examined by immunofluorescence and confocal analysis. Several strategies were used to verify the dynamic changes in macrophages. Immunofluorescence and confocal assays were performed on choroidal flat mounts to evaluate the morphology and phenotype of macrophages in different CNV phases, and the results were further verified by western blotting and RT-PCR. RESULTS: The location of infiltrated macrophages changed after laser injury in the CNV mouse model, and macrophage morphology also dynamically changed. Branching macrophages gradually shifted to become round with the progression of CNV, which was certified to be an M2 phenotypic shift. CONCLUSIONS: Dynamic changes in macrophage morphology were observed during CNV formation, and the round-shaped M2 phenotype could promote neovascularization. In general, the changes in morphology we observed in this study can help us to understand the critical role of macrophages in CNV progression and exploit a potential treatment option for CNV indicated by a shift in macrophage polarity.


Assuntos
Neovascularização de Coroide , Humanos , Camundongos , Animais , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Corioide/patologia , Lasers , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
10.
Comput Biol Med ; 166: 107546, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37826952

RESUMO

Cervical cancer, the second most common female malignant tumor, seriously threatens women's health and lives. Despite the availability of the HPV vaccine, effective treatment options for cervical cancer are still lacking. New research perspectives now clarify that RNA editing dysregulation and changes in circRNA expression are jointly involved in disease pathogenesis, so molecular changes associated with circRNA and RNA editing may provide clues for the development of new therapeutic strategies for cervical cancer. In this study, we designed a series of pipelines to identify and analyze dysregulated RNA editing events in circRNAs. Our findings indicate a decrease in A-to-I RNA editing levels in cervical cancer compared to normal tissues, and editing may influence the back-splicing process of circRNAs through structural modifications of Alu elements. Moreover, our research reveals that RNA editing could modulate circRNA biogenesis by influencing RNA binding protein (RBP) binding on a transcriptome-wide scale, as well as influence the expression and coding potential of circRNAs. Importantly, we identified three RNA editing sites that could serve as potential biomarkers. In summary, our study presents a comprehensive landscape of RNA editing perturbations in circRNAs, providing new insights into the complex relationship between RNA editing and circRNA dysregulation in cervical cancer.

11.
BMC Oral Health ; 23(1): 589, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620826

RESUMO

BACKGROUND: The effects of horizontal platelet-rich fibrin (H-PRF) bone block on the healing and immune response during sinus augmentation have not been fully investigated histologically at early time points. METHODS: Eighteenth male New Zealand white rabbits underwent bilateral sinus augmentation and were divided into two groups: deproteinized bovine bone mineral (DBBM) alone and H-PRF + DBBM (H-PRF bone block) group. Maxilla samples were collected at 3, 7 and 14 days post sinus augmentation procedures and analyzed using histological staining for the number of inflammatory cells, new blood vessels and evidence for early osteoclast bone turnover/remodeling. Furthermore, the effects of H-PRF bone blocks on the migration of osteoblasts and THP-1 macrophages were evaluated using a Transwell assay in vitro. RESULTS: A higher number of immune cells were found in the H-PRF bone block group at 3 and 7 days post-surgery when compared to the DBBM alone group,most notably in the regions close to the mucosal lining and bone plates. Furthermore, a significantly greater number of new blood vessel formations and early signs of osteoclast development were found in the H-PRF bone block group at 14 days. The in vitro transwell assay further confirmed that culture medium from H-PRF bone block markedly promote the migration of osteoblasts and THP-1 macrophages. CONCLUSIONS: The findings from this study have shown that H-PRF bone block is capable of increasing early immune cell infiltration leading to the acceleration of neovascularization and speeding the process of bone metabolism in vivo following maxillary sinus grafting with DBBM.


Assuntos
Produtos Biológicos , Fibrina Rica em Plaquetas , Masculino , Animais , Bovinos , Coelhos , Seio Maxilar/cirurgia , Maxila/cirurgia
12.
Periodontol 2000 ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37614160

RESUMO

Gold nanocages (AuNCs) have been invented and developed over two decades as biomaterial in clinical medicine with great application potential. AuNCs have a characteristic structure of porous walls with hollow interior and a compact size. This makes it possible for them to transport biomolecules or drugs with the advantages of their photothermal effects that could help further destroy germs or tumors while also regulating the release of drugs inside. Furthermore, their bioactivity and application can be broadened by using cell-membrane display technology. AuNCs have shown tremendous potential in antibacterial activity, inflammation modulation, and tissue regeneration, which is required in periodontitis and peri-implantitis treatment. Thus, this article provides an overview of AuNCs synthesis, characteristics, surface modifications, and clinical applications, aiming to serve as a reference for the design and fabrication of AuNCs-based smart materials for periodontal or peri-implant application.

13.
World J Oncol ; 14(4): 246-254, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37560338

RESUMO

Background: The F-box protein 43 (FBXO43), also referred to as endogenous meiotic inhibitor 2 (EMI2), has been linked to the advancement of various types of cancer, such as hepatocellular carcinoma, breast cancer, cholangiocarcinoma, and gastric cancer. Nevertheless, the precise function of FBXO43 in colorectal cancer (CRC) remains unclear. This study employed data from The Cancer Genome Atlas (TCGA) and clinical specimens to analyze the expression, prognostic value, and chemotherapeutic advantages of FBXO43 in CRC. Methods: Level 3 RNA sequencing data pertaining to 631 cases of colon and rectal adenocarcinomas (COAD-READ) were downloaded from TCGA. The data were utilized to analyze the expression, prognosis, and related signal pathways of FBXO43. The expression of FBXO43 in clinical samples was subsequently confirmed through the use of real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Lastly, a tissue microarray (TMA) consisting of 120 cases of CRC and corresponding normal tissues was established to investigate the relationship between FBXO43 and survival outcomes. Results: Results from both the TCGA analysis and clinical samples indicated that FBXO43 was significantly upregulated in CRC tissues in comparison to normal tissues. Moreover, high level of FBXO43 was found to be relevant to malignant clinical features, such as differentiation, lymph node metastasis, and pathological stage, as well as unfavorable prognosis in CRC patients. Subgroup analysis further demonstrated that FBXO43 could be an effective parameter for stratifying low-risk CRC patients. Notably, survival analysis showed that patients with high level of FBXO43 had worse overall survival (OS) and disease-free survival (DFS) following adjuvant chemotherapy, and FBXO43 was distinctly upregulated in chemotherapy-resistant patients' primary CRC tissues. Conclusions: FBXO43 was upregulated and associated with poor prognosis of CRC; patients with high expression of FBXO43 may not be benefit from adjuvant chemotherapy.

14.
Brief Bioinform ; 24(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37419612

RESUMO

Missing values (MVs) can adversely impact data analysis and machine-learning model development. We propose a novel mixed-model method for missing value imputation (MVI). This method, ProJect (short for Protein inJection), is a powerful and meaningful improvement over existing MVI methods such as Bayesian principal component analysis (PCA), probabilistic PCA, local least squares and quantile regression imputation of left-censored data. We rigorously tested ProJect on various high-throughput data types, including genomics and mass spectrometry (MS)-based proteomics. Specifically, we utilized renal cancer (RC) data acquired using DIA-SWATH, ovarian cancer (OC) data acquired using DIA-MS, bladder (BladderBatch) and glioblastoma (GBM) microarray gene expression dataset. Our results demonstrate that ProJect consistently performs better than other referenced MVI methods. It achieves the lowest normalized root mean square error (on average, scoring 45.92% less error in RC_C, 27.37% in RC_full, 29.22% in OC, 23.65% in BladderBatch and 20.20% in GBM relative to the closest competing method) and the Procrustes sum of squared error (Procrustes SS) (exhibits 79.71% less error in RC_C, 38.36% in RC full, 18.13% in OC, 74.74% in BladderBatch and 30.79% in GBM compared to the next best method). ProJect also leads with the highest correlation coefficient among all types of MV combinations (0.64% higher in RC_C, 0.24% in RC full, 0.55% in OC, 0.39% in BladderBatch and 0.27% in GBM versus the second-best performing method). ProJect's key strength is its ability to handle different types of MVs commonly found in real-world data. Unlike most MVI methods that are designed to handle only one type of MV, ProJect employs a decision-making algorithm that first determines if an MV is missing at random or missing not at random. It then employs targeted imputation strategies for each MV type, resulting in more accurate and reliable imputation outcomes. An R implementation of ProJect is available at https://github.com/miaomiao6606/ProJect.


Assuntos
Algoritmos , Genômica , Teorema de Bayes , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Espectrometria de Massas/métodos
15.
Acta Biomater ; 168: 551-564, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37414113

RESUMO

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Mitocôndrias/metabolismo , Nanopartículas/uso terapêutico , Nanopartículas/química , Imagem Óptica/métodos , Ferritinas/farmacologia
16.
Kaohsiung J Med Sci ; 39(9): 916-926, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37338034

RESUMO

The blood-retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague-Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK-8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)-affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose-induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Ratos , Animais , Retinopatia Diabética/genética , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genética , Gliose , Glucose/farmacologia
17.
J Cataract Refract Surg ; 49(8): 858-863, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37350758

RESUMO

PURPOSE: To explore clinical indicators to predict perceived pain during second-eye phacoemulsification surgery in patients with bilateral cataracts. SETTING: Shanghai General Hospital, China. DESIGN: A case‒control study and a prospective cohort study. METHODS: Patients with age-related cataract who underwent first-eye or second-eye uneventful phacoemulsification surgery were enrolled. Before surgery, ocular examination results, including vessel area density (VAD) and vessel skeleton density (VSD), obtained by optical coherence tomography angiography examination of the iris were performed. Patients completed a visual analog scale pain survey 3 times postoperatively: 1 hour, 3 hours, and 24 hours postoperatively. RESULTS: 70 patients were enrolled in the case‒control study, and the pain scores of the second-eye surgery group under local anesthesia were significantly greater than those of the first-eye surgery group ( P = .0005). Preoperative iris VAD in the second-eye group affected perioperative pain scores ( P = .0047). The optimal cutoff value of VAD was 0.2167 with a specificity of 76% and a sensitivity of 62%. In the prospective cohort study, 124 patients were included in the second-eye group. Preoperative iris VAD ( P = .0361) and the time interval ( P = .0221) were independent factors for second-eye surgery pain. Combined with preoperative iris VAD and surgical interval, the negative predictive value and positive predictive value were 0.95 and 0.29 for predicting moderate pain or above, the sensitivity and specificity were 0.97 and 0.23, respectively. CONCLUSIONS: The combination of iris VAD and the time interval between both eye surgeries can be an effective method to predict the timing of the second-eye cataract surgery and to avoid intraoperative pain.


Assuntos
Extração de Catarata , Catarata , Facoemulsificação , Humanos , Estudos Prospectivos , Estudos de Casos e Controles , China , Iris , Extração de Catarata/métodos , Dor , Percepção da Dor
18.
IEEE J Biomed Health Inform ; 27(2): 598-607, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35724285

RESUMO

Analysis of high dimensional biomedical data such as microarray gene expression data and mass spectrometry images, is crucial to provide better medical services including cancer subtyping, protein homology detection, etc. Clustering is a fundamental cognitive task which aims to group unlabeled data into multiple clusters based on their intrinsic similarities. However, for most clustering methods, including the most widely used K-means algorithm, all features of the high dimensional data are considered equally in relevance, which distorts the performance when clustering high-dimensional data where there exist many redundant variables and correlated variables. In this paper, we aim at addressing the problem of the high dimensional bioinformatics data clustering and propose a new correlation induced clustering, CoIn, to capture complex correlations among high dimensional data and guarantee the correlation consistency within each cluster. We evaluate the proposed method on a high dimensional mass spectrometry dataset of liver cancer tumor to explore the metabolic differences on tissues and discover the intra-tumor heterogeneity (ITH). By comparing the results of baselines and ours, it has been found that our method produces more explainable and understandable results for clinical analysis, which demonstrates the proposed clustering paradigm has the potential with application to knowledge discovery in high dimensional bioinformatics data.


Assuntos
Algoritmos , Neoplasias Hepáticas , Humanos , Biologia Computacional/métodos , Análise por Conglomerados , Cognição
19.
Front Oncol ; 13: 1298684, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38304038

RESUMO

Juxtaglomerular cell tumor (JCT) is an endocrine tumor marked by elevated renin levels and high blood pressure. This case report presents the clinical findings of a 47-year-old woman with a history of recurrent hypokalemia, headaches, hypertension, and increased plasma renin activity (PRA). Dynamic enhanced magnetic resonance imaging (MRI) revealed a small nodule on the upper part of the right kidney. Selective renal venous sampling indicated a higher PRA only in the right upper pole renal vein. The patient underwent surgical removal of the right kidney mass, and the pathology results confirmed the diagnosis of JCT. This case underscores the importance of conducting selective renal venous sampling for accurate JCT diagnosis.

20.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36232778

RESUMO

Cervical cancer has high morbidity and mortality rates, affecting hundreds of thousands of women worldwide and requiring more accurate screening for early intervention and follow-up treatment. Cytology is the current dominant clinical screening approach, and though it has been used for decades, it has unsatisfactory sensitivity and specificity. In this work, fluorescence lifetime imaging microscopy (FLIM) was used for the imaging of exfoliated cervical cells in which an endogenous coenzyme involved in metabolism, namely, reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H], was detected to evaluate the metabolic status of cells. FLIM images from 71 participants were analyzed by the unsupervised machine learning method to build a prediction model for cervical cancer risk. The FLIM method combined with unsupervised machine learning (FLIM-ML) had a sensitivity and specificity of 90.9% and 100%, respectively, significantly higher than those of the cytology approach. One cancer recurrence case was predicted as high-risk several months earlier using this method as compared to using current clinical methods, implying that FLIM-ML may be very helpful for follow-up cancer care. This study illustrates the clinical applicability of FLIM-ML as a detection method for cervical cancer screening and a convenient tool for follow-up cancer care.


Assuntos
NAD , Neoplasias do Colo do Útero , Detecção Precoce de Câncer , Feminino , Humanos , Microscopia de Fluorescência/métodos , NAD/metabolismo , NADP/metabolismo , Recidiva Local de Neoplasia , Fosfatos , Aprendizado de Máquina não Supervisionado , Neoplasias do Colo do Útero/diagnóstico por imagem
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