Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 830
Filtrar
1.
Med Image Anal ; 99: 103342, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39260034

RESUMO

Ovarian cancer, predominantly epithelial ovarian cancer (EOC), is a global health concern due to its high mortality rate. Despite the progress made during the last two decades in the surgery and chemotherapy of ovarian cancer, more than 70% of advanced patients are with recurrent cancer and disease. Bevacizumab is a humanized monoclonal antibody, which blocks VEGF signaling in cancer, inhibits angiogenesis and causes tumor shrinkage, and has been recently approved by the FDA as a monotherapy for advanced ovarian cancer in combination with chemotherapy. Unfortunately, Bevacizumab may also induce harmful adverse effects, such as hypertension, bleeding, arterial thromboembolism, poor wound healing and gastrointestinal perforation. Given the expensive cost and unwanted toxicities, there is an urgent need for predictive methods to identify who could benefit from bevacizumab. Of the 18 (approved) requests from 5 countries, 6 teams using 284 whole section WSIs for training to develop fully automated systems submitted their predictions on a test set of 180 tissue core images, with the corresponding ground truth labels kept private. This paper summarizes the 5 qualified methods successfully submitted to the international challenge of automated prediction of treatment effectiveness in ovarian cancer using the histopathologic images (ATEC23) held at the 26th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) in 2023 and evaluates the methods in comparison with 5 state of the art deep learning approaches. This study further assesses the effectiveness of the presented prediction models as indicators for patient selection utilizing both Cox proportional hazards analysis and Kaplan-Meier survival analysis. A robust and cost-effective deep learning pipeline for digital histopathology tasks has become a necessity within the context of the medical community. This challenge highlights the limitations of current MIL methods, particularly within the context of prognosis-based classification tasks, and the importance of DCNNs like inception that has nonlinear convolutional modules at various resolutions to facilitate processing the data in multiple resolutions, which is a key feature required for pathology related prediction tasks. This further suggests the use of feature reuse at various scales to improve models for future research directions. In particular, this paper releases the labels of the testing set and provides applications for future research directions in precision oncology to predict ovarian cancer treatment effectiveness and facilitate patient selection via histopathological images.

2.
J Microbiol Methods ; 226: 107030, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245370

RESUMO

Mycoplasma genitalium (MG) is an important sexually transmitted pathogen that can cause urethritis in males and pelvic inflammatory disease in females. Due to its complex growth requirements and lengthy incubation times, culturing MG in clinical laboratories is impractical. Here we describe a rapid and visual assay combining recombinase polymerase amplification (RPA) with lateral flow (LF) strips to detect MG (MG-RPA-LF). The limit of detection (LoD) of this method was 33.6 genome equivalents (GE) per reaction, using a dilution series of purified genomic DNA. Clinical performance was evaluated by testing 100 urogenital swabs. Compared to the Simultaneous Amplification and Testing assay, our MG-RPA-LF assay showed a sensitivity of 94 % (95 % CI, 82 %-98 %) and a specificity of 100 % (95 % CI, 91 %-100 %). The overall concordance between the two methods was 97 % (95 % CI, 91 %-99 %) with a κ coefficient of 0.94 (P < 0.001). Without cumbersome and expensive instruments, this method is anticipated to be a promising alternative to diagnose MG infection, especially in resource-poor settings.

3.
Crit Rev Anal Chem ; : 1-23, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264749

RESUMO

Hypochlorous acid (HClO) is widely used in everyday life for bleaching and disinfecting tap water, and also in human metabolism, where it plays an important role in destroying foreign bacterial invaders and pathogens as well as immune defense and cellular functioning maintenance. Abnormal levels of hypochlorous acid have the potential to cause joint inflammation, neuronal degeneration, and even life-threatening cancer. Specific identification and effective detection of hypochlorous acid are important for monitoring human health and the environment. In recent years, organic fluorescent probes have attracted much attention because of their simple synthesis, easy operation, high sensitivity, and high specificity, and a variety of hypochlorous acid fluorescent probes based on low-cost, easy-to-operate, and rapid identification have been developed. In this paper, we review the fluorescent probes that have been developed in the past five years for the specific recognition of hypochlorous acid based on different fluorophores, such as triphenylamine, coumarin, 1,8-naphthalize, etc., as well as recognition units, such as N-N dimethyl thiosemicarbazone, and describe how the probes and hypochlorous acid interact for identification in the same manner as other fluorescent probes. In addition, the reaction mechanism between the probe and hypochlorous acid, the fluorescence change of the probe, and the detection limit are described to illustrate the progress in the detection of hypochlorous acid in recent years and to provide ideas for the development of hypochlorous acid fluorescent probes in the future.

4.
BMC Cancer ; 24(1): 1106, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237882

RESUMO

BACKGROUND: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). METHODS: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. RESULTS: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion. CONCLUSIONS: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels.


Assuntos
Neoplasias dos Ductos Biliares , Antígeno CA-19-9 , Colangiocarcinoma , Hepatectomia , Linfócitos , Recidiva Local de Neoplasia , Neutrófilos , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/sangue , Colangiocarcinoma/patologia , Colangiocarcinoma/mortalidade , Masculino , Feminino , Neutrófilos/patologia , Pessoa de Meia-Idade , Prognóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/mortalidade , Estudos Retrospectivos , Linfócitos/patologia , Antígeno CA-19-9/sangue , Idoso , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Adulto , Período Pré-Operatório , Contagem de Linfócitos , Fatores de Risco
5.
Adv Mater ; : e2409606, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340284

RESUMO

Electromagnetic radiation (EMR) is a ubiquitous harm and hard to detect dynamically in multiple scenarios. A mechano-photothermal cooperative microfiber film (MFF) actuator is developed that can synchronously detect EMR with high reliability. The programmable actuation is deployed by a hot-pressing methodology, achieving the MFF with moderate modulus (378 MPa) and superior toughness (87.26 MJ m-3) that ensure superior response (0.068 cm-1 s-1) and bending curvature (0.63 cm-1). A secondary hot-pressing can further program the actuation behavior with black phosphorus local photothermal enhancement patterns to achieve 2D-3D transformable geometries. An amphibious robot with a land-water adaptive locomotion mechanism is designed by programming the MFFs. It can crawl on land and locomote on water with a velocity up to ≈1.8 mm s-1, and ≈2.39 cm s-1, respectively. Employing the conductive fabric layer of the actuator with electromagnetic induction effect, the amphibious robot can synchronously perceive environmental EMR with sensitivity up to 99.73% ± 0.15% during locomotion, with superior adaptability to EMR source intensity (0.1 to 3000 W) and distance (≈9 m) compared to a commercial EMR detector. This EMR detective microfiber actuator can inspire a new direction of environment-interactive smart materials, and soft robots with multi-scenario adaptivity and autonomous environment perceptivity.

6.
RSC Adv ; 14(40): 29384-29394, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39285871

RESUMO

Water treatment faces significant challenges due to the increasing complexity of pollutants and the need for more efficient, sustainable treatment methods. However, current adsorbent materials often struggle with issues such as low adsorption capacity, slow kinetics, and poor reusability, limiting their practical application. In this study, we developed a novel hierarchical porous hybrid gel (HPHG) for water treatment to address the limitations of conventional adsorbents. The HPHG features a multi-level porous structure (from 48 ± 28 nm to 4385 ± 823 nm) that significantly enhances its porosity and specific surface area. We systematically investigated the relationship between the material's structure and its adsorption performance. Kinetic studies revealed a tendency towards a pseudo-second-order adsorption model, attributed to the material's unique structural features that facilitate rapid mass exchange channels inside HPHG and provide abundant active sites for pollutant adsorption. Reusability tests demonstrated that the material retained 85.4% of its initial adsorption capacity after five adsorption-desorption cycles, highlighting its potential for practical applications. This study provides valuable insights into structure-performance relationships in advanced water treatment materials, offering a promising approach for designing next-generation adsorbents with superior efficiency and sustainability.

7.
Mech Ageing Dev ; 222: 111978, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233064

RESUMO

BACKGROUND: Stimulator of interferons genes (STING) is crucial for innate immune response. It has been demonstrated that cGAS-STING pathway was the driver of aging-related inflammation. However, whether STING is involved in cardiac dysfunction during the physiological aging process remains unclear. METHODS: Gene expression profiles were obtained from the Gene Expression Omnibus database, followed by weighted gene co-expression network analysis, gene ontology analysis and protein network interaction analysis to identify key pathway and genes associated with aging. The effects of STING on cardiac function, glucose homeostasis, inflammation, and autophagy in physiological aging were investigated with STING knockout mice. RESULTS: Bioinformatics analysis revealed STING emerged as a hub gene of interest. Subsequent experiments demonstrated the activation of STING pathway in the heart of aged mice. Knockout of STING alleviated the inflammation in aged mice. However, Knockout of STING impaired glucose tolerance, inhibited autophagy, enhanced oxidative stress and aggravated cardiac dysfunction in aged mice. CONCLUSION: Although reducing inflammation, long-term STING inhibition by genetic ablation exacerbated cardiac dysfunction in aged mice. Given the multifaceted nature of aging and the diverse cellular functions of STING beyond immune regulation, the negative effects of targeting STING as a strategy to mitigate aging phenotype should be fully considered.

8.
Carbohydr Polym ; 346: 122644, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39245531

RESUMO

A complex heteropolysaccharide SCP-2 named schisanan B (Mw = 1.005 × 105 g/mol) was obtained from water extracts of Schisandra chinensis fruits, and its planar structure was finally deduced as a galacturonoglucan by a combination of monosaccharide compositions, methylation analysis, partial acid hydrolysis, enzymatic hydrolysis and 1D/2D-nuclear magnetic resonance spectroscopy. The conformation of SCP-2 exhibited a globular shape with branching in ammonium formate aqueous solutions. The rheological properties of SCP-2 were investigated on concentrations, temperature, pH and salts. The in vitro immunomodulatory activity assay demonstrated that SCP-2 significantly enhanced the production of nitric oxide (NO) and stimulated the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in macrophages. Through a combination of high-resolution live-cell imaging, surface plasmon resonance, and molecular docking techniques, SCP-2 exhibited a strong binding affinity with the Toll-like receptor 4 (TLR4). Moreover, western blot analysis revealed that SCP-2 effectively induced downstream signaling proteins associated with TLR4 activation, thereby promoting macrophage activation. The evidence strongly indicates that TLR4 functions as a membrane protein target in the activation of macrophages and immune regulation induced by SCP-2.


Assuntos
Frutas , Reologia , Schisandra , Receptor 4 Toll-Like , Schisandra/química , Camundongos , Frutas/química , Células RAW 264.7 , Animais , Receptor 4 Toll-Like/metabolismo , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Pectinas/química , Fator de Necrose Tumoral alfa/metabolismo , Glucanos/química , Interleucina-6/metabolismo
9.
Zhen Ci Yan Jiu ; 49(8): 829-835, 2024 Aug 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39318312

RESUMO

OBJECTIVES: To observe the effect of electroacupuncture (EA) on pain, anxiety like behavior, and substance P(SP) /neurokinin-1 receptor (NK1R) /ß -arrestin 1(ARRB1) pathway related protein expression in hippocampus of chronic constriction injury (CCI) rats, so as to explore its mechanisms underlying improvement of neuropathic pain. METHODS: Twenty-seven male SD rats were randomly divided into sham operation, model and EA groups, with 9 rats in each group. The CCI model was established by ligature of the left sciatic nerve. On the 8th day following modeling, EA (2 Hz, 0.5-1.5 mA) was applied to the left "Huantiao" (GB34) and "Yanglingquan" (GB34) for 30 min, once every other day for 13 times. Mechanical paw withdrawal threshold (MWT), thermal paw withdrawal threshold (TWL) and difference of the weight distribution of the hind limbs were detected before operation and at the 5th, 9th, 17th, 25th and 33rd days after operation. Open field test was used to evaluate the anxiety-like behavior of rats. The content of SP in hippocampus was determined by ELISA. The protein expression of NK1R and ARRB1 in hippocampus was detected by Western blot. RESULTS: Compared with the sham operation group, the MWT and TWL of the left hind limb at the 5th, 9th, 17th, 25th and 33rd days after operation, the time of entering the central area and the total distance of movement, and the content of SP in the hippocampus were significantly decreased (P<0.001, P<0.01), while the difference of the weight distribution of the hind limbs at the 5th, 9th, 17th, 25th and 33rd days after operation and the protein expression of NK1R and ARRB1 were significantly increased (P<0.001, P<0.05) in the model group. After EA intervention, the MWT and TWL of the left hind limb, the time of entering the central area and the total moving distance, and the expression of SP in the hippocampus were significantly increased (P<0.01, P<0.001, P<0.05), while the difference in the weight distribution of the hind limbs was significantly reduced, and the expression of NK1R and ARRB1 protein in the hippocampus were significantly decreased (P<0.001, P<0.05) in the EA group. CONCLUSIONS: EA can effectively improve the pain and anxiety behaviors in CCI rats, and reverse the abnormal expression of SP, NK1R and ARRB1 proteins in the hippocampus, which may be related to its effects in regulating the SP/NK1R/ARRB1 pathway in the hippocampus.


Assuntos
Eletroacupuntura , Hipocampo , Neuralgia , Ratos Sprague-Dawley , Receptores da Neurocinina-1 , Substância P , Animais , Masculino , Ratos , Hipocampo/metabolismo , Neuralgia/terapia , Neuralgia/metabolismo , Neuralgia/genética , Receptores da Neurocinina-1/metabolismo , Receptores da Neurocinina-1/genética , Humanos , Substância P/metabolismo , Substância P/genética , beta-Arrestina 1/metabolismo , beta-Arrestina 1/genética , Pontos de Acupuntura , Transdução de Sinais
10.
J Transl Med ; 22(1): 741, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107784

RESUMO

BACKGROUND: Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). PURPOSE: To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments. METHODS: BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1ß. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo. RESULTS: BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/ß-catenin signaling, regardless of IL-1ß presence or duration of exposure. This inhibition of the Wnt/ß-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure. CONCLUSIONS: PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/ß-catenin signaling, irrespective of inflammatory conditions.


Assuntos
Condrogênese , Campos Eletromagnéticos , Células-Tronco Mesenquimais , Via de Sinalização Wnt , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Proliferação de Células , Masculino , Movimento Celular , Interleucina-1beta/metabolismo , Regulação da Expressão Gênica/efeitos da radiação , Ratos Sprague-Dawley
11.
Cancer Lett ; 604: 217199, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39216547

RESUMO

Macrophages play a multifaceted role in cancer biology, with both pro-tumorigenic and anti-tumorigenic functions. Understanding the mechanisms underlying macrophage involvement in cancer progression is essential for the development of therapeutic strategies. Our study analyzed single-cell RNA sequencing data from 12 patients with liver cancer and identified a subpopulation of macrophages characterized by elevated expression of SPP1, which correlates with poor prognosis in liver cancer patients. These SPP1+ macrophages induce upregulation of tumor stemness through a vitronectin (VTN)-dependent paracrine mechanism. Mechanistically, VTN derived from SPP1+ macrophages promote integrin αvß5/adenosine 5'-monophosphate-activated protein kinase (AMPK)/Yes-associated protein 1 (YAP1)/SYR-box transcription factor 4 (SOX4) signaling, mediating liver tumor stemness and progression. Conversely, CCL15 produced by liver cancer cells drives polarization of M0 macrophages toward an SPP1+ macrophage phenotype, establishing a positive feedback loop of macrophage-tumor stemness. Furthermore, the presence of SPP1+ macrophages confers chemoresistance in liver cancer, and inhibition of the macrophage-tumor feedback loop through targeting integrin αvß5/YAP1 signaling sensitizes liver cancer cells to chemotherapy. Our study highlights the crucial role of SPP1+ macrophages in liver cancer progression, providing novel insights for clinical liver cancer therapy.

12.
IEEE Trans Med Imaging ; PP2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088492

RESUMO

Semi-supervised learning (SSL) has been proven beneficial for mitigating the issue of limited labeled data, especially on volumetric medical image segmentation. Unlike previous SSL methods which focus on exploring highly confident pseudo-labels or developing consistency regularization schemes, our empirical findings suggest that differential decoder features emerge naturally when two decoders strive to generate consistent predictions. Based on the observation, we first analyze the treasure of discrepancy in learning towards consistency, under both pseudo-labeling and consistency regularization settings, and subsequently propose a novel SSL method called LeFeD, which learns the feature-level discrepancies obtained from two decoders, by feeding such information as feedback signals to the encoder. The core design of LeFeD is to enlarge the discrepancies by training differential decoders, and then learn from the differential features iteratively. We evaluate LeFeD against eight state-of-the-art (SOTA) methods on three public datasets. Experiments show LeFeD surpasses competitors without any bells and whistles, such as uncertainty estimation and strong constraints, as well as setting a new state of the art for semi-supervised medical image segmentation. Code has been released at https://github.com/maxwell0027/LeFeD.

13.
Med Image Anal ; 98: 103304, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39173412

RESUMO

Masked Image Modelling (MIM), a form of self-supervised learning, has garnered significant success in computer vision by improving image representations using unannotated data. Traditional MIMs typically employ a strategy of random sampling across the image. However, this random masking technique may not be ideally suited for medical imaging, which possesses distinct characteristics divergent from natural images. In medical imaging, particularly in pathology, disease-related features are often exceedingly sparse and localized, while the remaining regions appear normal and undifferentiated. Additionally, medical images frequently accompany reports, directly pinpointing pathological changes' location. Inspired by this, we propose Masked medical Image Modelling (MedIM), a novel approach, to our knowledge, the first research that employs radiological reports to guide the masking and restore the informative areas of images, encouraging the network to explore the stronger semantic representations from medical images. We introduce two mutual comprehensive masking strategies, knowledge-driven masking (KDM), and sentence-driven masking (SDM). KDM uses Medical Subject Headings (MeSH) words unique to radiology reports to identify symptom clues mapped to MeSH words (e.g., cardiac, edema, vascular, pulmonary) and guide the mask generation. Recognizing that radiological reports often comprise several sentences detailing varied findings, SDM integrates sentence-level information to identify key regions for masking. MedIM reconstructs images informed by this masking from the KDM and SDM modules, promoting a comprehensive and enriched medical image representation. Our extensive experiments on seven downstream tasks covering multi-label/class image classification, pneumothorax segmentation, and medical image-report analysis, demonstrate that MedIM with report-guided masking achieves competitive performance. Our method substantially outperforms ImageNet pre-training, MIM-based pre-training, and medical image-report pre-training counterparts. Codes are available at https://github.com/YtongXie/MedIM.


Assuntos
Aprendizado de Máquina Supervisionado , Humanos , Processamento de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/métodos , Algoritmos
14.
J Nanobiotechnology ; 22(1): 525, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217329

RESUMO

The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction.


Assuntos
Regeneração Óssea , Ossos Faciais , Hidrogéis , Nanoestruturas , Engenharia Tecidual , Hidrogéis/química , Humanos , Nanoestruturas/química , Animais , Regeneração Óssea/efeitos dos fármacos , Engenharia Tecidual/métodos , Crânio/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Materiais Biocompatíveis/química , Alicerces Teciduais/química
15.
Phytomedicine ; 132: 155792, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39059090

RESUMO

BACKGROUND: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear. PURPOSE: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides. METHODS: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI+-MS, CETSA, immunoblot and SPR assay. The RAW264.7Clec4G-RFP and RAW264.7Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects. RESULTS: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects. CONCLUSION: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis.


Assuntos
Pectinas , Animais , Camundongos , Pectinas/farmacologia , Lectinas Tipo C/metabolismo , Células RAW 264.7 , Metabolismo Energético/efeitos dos fármacos , Polissacarídeos/farmacologia
16.
Glycoconj J ; 41(3): 201-216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38954268

RESUMO

A glucosyl-rich pectin, JMMP-3 (Mw, 2.572 × 104 g/mol, O-methyl % = 3.62%), was isolated and purified from the pericarp of the immature fruit of Juglans mandshurica Maxim. (QingLongYi). The structure of JMMP-3 was studied systematically by infrared spectroscopy, monosaccharide compositions, methylation analysis, partial acid hydrolysis, and 1/2D-NMR. The backbone of JMMP-3 possessed a smooth region (→ 4GalA1 →) and a hairy region (→ 4GalA1 → 2Rha1 →) with a molar ratio of 2: 5. The substitution of four characteristic side chains (R1-R4) occurs at C-4 of → 2,4)-α-Rhap-(1→, where R1 is composed of → 5)-α-Araf-(1→, R2 is composed of → 4)-ß-Galp-(1 → and ß-Galp-(1→, R3 is composed of α-Glcp-(1→, →4)-α-Glcp-(1 → and → 4,6)-α-Glcp-(1→, and R4 is composed of → 5)-α-Araf-(1→, ß-Galp-(1→, → 4)-ß-Galp-(1→, → 3,4)-ß-Galp-(1→, → 4,6)-ß-Galp-(1 → and → 2,4)-ß-Galp-(1 → . In addition, the antitumor activity of JMMP-3 on HepG2 cells was preliminarily investigated.


Assuntos
Frutas , Juglans , Pectinas , Juglans/química , Pectinas/química , Pectinas/isolamento & purificação , Humanos , Frutas/química , Células Hep G2 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação
17.
Org Lett ; 26(31): 6766-6770, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39082870

RESUMO

A chiral Brønsted acid/Pd that cooperatively catalyzed the asymmetric cascade aza-Piancatelli rearrangement/hydroamination of readily accessible alkynyl-functionalized tertiary furylcarbinols with anilines has been developed. This protocol provides expedient access to a variety of densely functionalized cyclopenta[b]pyrroline derivatives in high yields with excellent enantioselectivities.

18.
Theranostics ; 14(9): 3526-3547, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948071

RESUMO

Background: Immunotherapy has demonstrated its potential to improve the prognosis of patients with hepatocellular carcinoma (HCC); however, patients' responses to immunotherapy vary a lot. A comparative analysis of the tumor microenvironment (TME) in responders and non-responders is expected to unveil the mechanisms responsible for the immunotherapy resistance and provide potential treatment targets. Methods: We performed sequencing analyses using 10x Genomics technology on six HCC patients who responded to anti-PD-1 therapy and one HCC patient who did not respond. Additionally, we obtained single cell data from untreated, responsive, and nonresponsive HCC patients from public databases, and used part of the datasets as a validation cohort. These data were integrated using algorithms such as Harmony. An independent validation cohort was established. Furthermore, we performed spatial transcriptomic sequencing on the tumor adjacent tissues of three HCC responsive patients using 10x Genomics spatial transcriptomic technology. Additionally, we analyzed data about three HCC patients obtained from public databases. Finally, we validated our conclusions using immunofluorescence, flow cytometry, and in vivo experiments. Results: Our findings confirmed the presence of "immune barrier" partially accounting for the limited efficacy of immunotherapy. Our analysis revealed a significant increase in TREM2+ Macrophages among non-responsive patients expressing multiple immunosuppressive signals. anti-Csf1r monoclonal antibodies effectively eliminated these macrophages and augmented the therapeutic effects of anti-PD-1 therapy. TCR+ Macrophages possessed direct tumor-killing capabilities. IL1B+ cDC2 was the primary functional subtype of cDC2 cells. Absence of THEMIShi CD8+ T subtypes might diminish immunotherapeutic effects. Furthermore, CD8+ T cells entered a state of stress after anti-PD-1 treatment, which might be associated with CD8+ T cell exhaustion and senescence. Conclusions: The profiles of immune TMEs showed differences in HCC patients responsive, non-responsive and untreated. These differences might explain the discounted efficacy of immunotherapy in some HCC patients. The cells and molecules, which we found to carry unique capabilities, may be targeted to enhance immunotherapeutic outcomes in patients with HCC.


Assuntos
Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Receptor de Morte Celular Programada 1 , Análise de Célula Única , Microambiente Tumoral , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Microambiente Tumoral/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia/métodos , Animais , Masculino , Camundongos , Feminino , Pessoa de Meia-Idade
19.
Front Pharmacol ; 15: 1416295, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948469

RESUMO

Introduction: Genomic profiling has revolutionized therapeutic interventions and the clinical management of liver cancer. However, pathogenetic mechanisms, molecular determinants of recurrence, and predictive biomarkers for first-line treatment (anti-PD-(L)1 plus bevacizumab) in liver cancer remain incompletely understood. Materials and methods: Targeted next-generation sequencing (tNGS) (a 603-cancer-gene panel) was applied for the genomic profiling of 232 hepatocellular carcinoma (HCC) and 22 intrahepatic cholangiocarcinoma (ICC) patients, among which 47 unresectable/metastatic HCC patients underwent anti-PD-1 plus bevacizumab therapy. Genomic alterations were estimated for their association with vascular invasion (VI), location of onset, recurrence, overall survival (OS), recurrence-free survival (RFS), and anti-PD-1 plus bevacizumab therapy response. Results: The genomic landscape exhibited that the most commonly altered genes in HCC were TP53, FAT3, PDE4DIP, KMT2C, FAT1, and MYO18A, while TP53, FAT1, FAT3, PDE4DIP, ROS1, and GALNT11 were frequently altered in ICC; notably, KRAS (18.18% vs. 1.29%) and BAP1 (13.64% vs. 1.29%) alterations were significantly more prevalent in ICC. Comparison analysis demonstrated the distinct clinicopathological/genomic characterizations between Chinese and Western HCC cohorts. Genomic profiling of HCC underlying VI showed that LDLR, MSH2, KDM5D, PDE3A, and FOXO1 were frequently altered in the VI group compared to patients without VIs. Compared to the right hepatic lobes of HCC patients, the left hepatic lobe of HCC patients had superior OS (median OS: 36.77 months vs. unreached, p < 0.05). By further comparison, Notch signaling pathway-related alterations were significantly prevalent among the right hepatic lobes of HCC patients. Of note, multivariate Cox regression analysis showed that altered RB1, NOTCH3, MGA, SYNE1, and ZFHX3, as independent prognostic factors, were significantly correlated with the OS of HCC patients. Furthermore, altered LATS1 was abundantly enriched in the HCC-recurrent group, and impressively, it was independent of clinicopathological features in predicting RFS (median RFS of altered type vs. wild-type: 5.57 months vs. 22.47 months, p < 0.01). Regarding those treated HCC patients, TMB value, altered PTPRZ1, and cell cycle-related alterations were identified to be positively associated with the objective response rate (ORR), but KMT2D alterations were negatively correlated with ORR. In addition, altered KMT2D and cell cycle signaling were significantly associated with reduced and increased time to progression-free survival (PFS), respectively. Conclusion: Comprehensive genomic profiling deciphered distinct molecular characterizations underlying VI, location of onset, recurrence, and survival time in liver cancer. The identification of novel genetic predictors of response to anti-PD-1 plus bevacizumab in HCC facilitated the development of an evidence-based approach to therapy.

20.
Artigo em Inglês | MEDLINE | ID: mdl-39083391

RESUMO

Self-supervised learning (SSL) opens up huge opportunities for medical image analysis that is well known for its lack of annotations. However, aggregating massive (unlabeled) 3D medical images like computerized tomography (CT) remains challenging due to its high imaging cost and privacy restrictions. In our pilot study, we advocated bringing a wealth of 2D images like chest X-rays as compensation for the lack of 3D data, aiming to build a universal medical self-supervised representation learning framework, called UniMiSS. Especially, we designed a pyramid U- like medical Transformer (MiT) as the backbone to make UniMiSS possible to perform SSL with both 2D and 3D images. Consequently, the predecessor UniMiSS has two obvious merits compared to current 3D-specific SSL: (1) more effective - superior to learning strong representations, benefiting from more and diverse data; and (2) more versatile - suitable for various downstream tasks without the restriction on the dimensionality barrier. Unfortunately, UniMiSS did not dig deeply into the intrinsic anatomy correlation between 2D medical images and 3D volumes due to the lack of paired multi-modal/dimension patient data. In this extension paper, we propose the UniMiSS+, in which we introduce the digitally reconstructed radiographs (DRR) technology to simulate X-ray images from a CT volume to access paired CT and X-ray data. Benefiting from the paired group, we introduce an extra pair- wise constraint to boost the cross-modality correlation learning, which also can be adopted as a cross-dimension regularization to further improve the representations. We conduct expensive experiments on multiple 3D/2D medical image analysis tasks, including segmentation and classification. The results show that the proposed UniMiSS+ achieves promising performance on various downstream tasks, not only outperforming the ImageNet pre-training and other advanced SSL counterparts substantially but also improving the predecessor UniMiSS pre-training. Code is available at: https://github.com/YtongXie/UniMiSS-code.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA