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1.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385879

RESUMO

Accurate prediction of antibody-antigen complex structures is pivotal in drug discovery, vaccine design and disease treatment and can facilitate the development of more effective therapies and diagnostics. In this work, we first review the antibody-antigen docking (ABAG-docking) datasets. Then, we present the creation and characterization of a comprehensive benchmark dataset of antibody-antigen complexes. We categorize the dataset based on docking difficulty, interface properties and structural characteristics, to provide a diverse set of cases for rigorous evaluation. Compared with Docking Benchmark 5.5, we have added 112 cases, including 14 single-domain antibody (sdAb) cases and 98 monoclonal antibody (mAb) cases, and also increased the proportion of Difficult cases. Our dataset contains diverse cases, including human/humanized antibodies, sdAbs, rodent antibodies and other types, opening the door to better algorithm development. Furthermore, we provide details on the process of building the benchmark dataset and introduce a pipeline for periodic updates to keep it up to date. We also utilize multiple complex prediction methods including ZDOCK, ClusPro, HDOCK and AlphaFold-Multimer for testing and analyzing this dataset. This benchmark serves as a valuable resource for evaluating and advancing docking computational methods in the analysis of antibody-antigen interaction, enabling researchers to develop more accurate and effective tools for predicting and designing antibody-antigen complexes. The non-redundant ABAG-docking structure benchmark dataset is available at https://github.com/Zhaonan99/Antibody-antigen-complex-structure-benchmark-dataset.


Assuntos
Algoritmos , Benchmarking , Humanos , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Complexo Antígeno-Anticorpo
2.
Chembiochem ; : e202400261, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819577

RESUMO

Autophagy is an important biological mechanism for eukaryotic cells to regulate growth, death, and energy metabolism, and plays an important role in removing damaged organelles, misfolded or aggregated proteins, and clearing pathogens. It has been found that autophagy is closely related to cell survival and death, and is of great significance in cancerigenesis and development, playing a bidirectional role in cancer inhibition and cancer promotion. Therefore, treating cancers by regulating autophagy has attracted much attention. A large amount of research evidence indicates that polymeric nanomaterials are able to regulate cellular autophagy, and their good biocompatibility, degradability, and functionalizable modification open up a broad application prospect for improving the therapeutic effect of cancers. This review provides an overview of the research progress of polymeric nanomaterials for modulating autophagy in the treatment of cancers.

3.
Environ Res ; 252(Pt 2): 118920, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657849

RESUMO

Long-term wastewater irrigation leads to the loss of calcium carbonate (CaCO3) in the tillage layer of calcareous land, which irreversibly damages the soil's ability to retain cadmium (Cd). In this study, we selected calcareous agricultural soil irrigated with wastewater for over 50 years to examine the recalcification effects of sugar beet factory lime (SBFL) at doses of 0%, 2.5%, 5%, and 10%. We found that SBFL promoted Cd transformation in the soil from active exchangeable species to more stable carbonate-bonded and residual species, which the X-ray diffraction patterns also confirmed results that CdSO4 reduced while CdS and CaCdCO3 increased. Correspondingly, the soil bioavailable Cd concentration was significantly reduced by 65.6-84.7%. The Cd concentrations in maize roots and shoots were significantly reduced by 11.7-50.6% and 13.0-70.0%, respectively, thereby promoting maize growth. Nevertheless, SBFL also increased the proportion of plant-unavailable phosphorus (P) in Ca8-P and Ca10-P by 4.3-13.0% and 10.7-25.9%, respectively, reducing the plant-available P (Olsen P) content by 5.2-22.1%. Consequently, soil P-acquiring associated enzyme (alkaline phosphatase) activity and microbial (Proteobacteria, Bacteroidota, and Actinobacteria) community abundance significantly increased. Our findings showed that adding SBFL to wastewater-irrigated calcareous soil stabilized Cd, but exacerbated P limitation. Therefore, it is necessary to alleviate P limitations in the practice of recalcifying degraded calcareous land.


Assuntos
Cádmio , Carbonato de Cálcio , Fósforo , Poluentes do Solo , Solo , Águas Residuárias , Zea mays , Cádmio/análise , Cádmio/química , Fósforo/análise , Águas Residuárias/química , Poluentes do Solo/análise , Poluentes do Solo/química , Solo/química , Zea mays/química , Carbonato de Cálcio/química , Irrigação Agrícola/métodos , Microbiologia do Solo , Óxidos , Compostos de Cálcio
4.
BMC Med Imaging ; 23(1): 28, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36747135

RESUMO

PURPOSE: The diagnosis of pulmonary hamartoma (PH) based on computed tomography (CT) is a challenge, especially in patients with atypical imaging characteristics. This study was aimed at summarizing the imaging characteristic of 18F-Fluoro-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) in PH and exploring the application value of PET-CT in the diagnosis of PH. DATA AND METHODS: Patients diagnosed with PH who had undergone PET-CT from literature pertaining were retrospectively analyzed, which were cases of publications from the Cochrane Library, PubMed, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI) and Wanfang databases, from 2008 to June 2022. The other 20 cases of the collection were patients from our hospital from 2008 to June 2022. Patients' symptoms, imaging characteristics of chest CT, PET-CT characteristics, the reason for PET-CT and the complications were analyzed. RESULTS: In this retrospective study, a total of 216 patients were diagnosed with PH and had been examined by PET-CT. 20 of the cases were patients of our hospital from January 2008 to June 2022. The other cases were collected from the literature. The mean diameter of most PH lesions is 1.7 ± 1.0 cm. The mean maximum standardized uptake value (SUVmax) of the PH lesions was 1.2 ± 1.1. Most of their SUVmax were lower than internationally recognized cut-off value (SUVmax = 2.5). PET-CT was superior to CT in the diagnosis of PH but there was a correlation of between CT diagnosis and PET-CT diagnosis for the PH lesions. In order to draw the Receiver operating characteristic (ROC), we selected 29 patients with a clear SUVmax value of their PH lesion, and 29 lung cancer patients with clear SUVmax value in our hospital were collected as a control group. ROC curve analysis showed that the area under curve (AUC) of SUVmax was 0.899, and the optimal diagnostic threshold was SUVmax > 2.65. PET-CT could distinguish PH from malignant lesions with a sensitivity of 89.66% by applying a SUVmax of 2.65 as a cut-off in this study. CONCLUSION: PET-CT might be a useful tool to diagnose PH, which shows a better diagnostic sensitivity than CT. But PET-CT can not be used as a single diagnostic approach, which should be combined with other methods and the patients' history to make the most correct diagnosis.


Assuntos
Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Fluordesoxiglucose F18 , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
5.
Cancer Sci ; 113(2): 733-743, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34859546

RESUMO

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer-caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel could be an effective strategy for inhibiting breast cancer metastasis. However, their inherent defects, in terms of short blood circulation half-life and lack of tumor targeting, not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by a nanodelivery system, and explore its mechanism. Herein, a paclitaxel-conjugated and mifepristone-loaded hydrogel (PM-nano) was prepared by self-assembly. Its characterizations were studied. The antimetastatic effect was evaluated in vitro and in vivo and its mechanism was also explored by western blot assay. The resultant PM-nano was developed with favorable water solubility and good biocompatibility. Moreover, PM-nano displayed increased cell uptake properties and stimulated drug release in the tumor micro-acidic environment. The PM-nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. The PM-nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase-like orphan receptor 1 and MMPs. Taken together, PM-nano showed superior antimetastatic effects against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for limiting metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hidrogéis/uso terapêutico , Mifepristona/uso terapêutico , Paclitaxel/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Disponibilidade Biológica , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Portadores de Fármacos/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Mifepristona/química , Mifepristona/farmacologia , Nanoestruturas/uso terapêutico , Paclitaxel/química , Paclitaxel/farmacologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Phytother Res ; 35(6): 3298-3309, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33570219

RESUMO

Abscisic acid (ABA), a well-known natural phytohormone reportedly exerts anti-inflammatory and anti-oxidative properties in diabetes and colitis. However, the efficacy of ABA against allergic airway inflammation and the underlying mechanism remain unknown. Herein, an OVA-induced murine allergic airway inflammation model was established and treated with ABA in the presence or absence of PPAR-γ antagonist GW9662. The results showed that ABA effectively stunted the development of airway inflammation, and concordantly downregulated OVA-induced activation of NLRP3 inflammasome, suppressed oxidative stress and decreased the expression of mitochondrial fusion/fission markers including Optic Atrophy 1 (OPA1), Mitofusion 2 (Mfn2), dynamin-related protein 1 (DRP1) and Fission 1 (Fis1). Moreover, ABA treatment further increased OVA-induced expression of PPAR-γ, while GW9662 abrogated the inhibitory effect of ABA on allergic airway inflammation as well as on the activation of NLRP3 inflammasome and oxidative stress. Consistently, ABA inhibited the activation of NLRP3 inflammasome, suppressed oxidative stress and mitochondrial fusion/fission in LPS-stimulated Raw264.7 cells via PPAR-γ. Collectively, ABA ameliorates OVA-induced allergic airway inflammation in a PPAR-γ dependent manner, and such effect of ABA may be associated with its inhibitory effect on NLRP3 inflammasome and oxidative stress. Our results suggest the potential of ABA or ABA-rich food in protecting against asthma.


Assuntos
Ácido Abscísico/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Asma/metabolismo , Feminino , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células RAW 264.7 , Sistema Respiratório/metabolismo
7.
Thorac Cancer ; 15(10): 820-829, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38409918

RESUMO

BACKGROUND: N-acetyltransferase 10 (NAT10) serves as a critical enzyme in mediating the N4-acetylcytidine (ac4C) that ensures RNA stability and effective translation processes. The role of NAT10 in driving the advancement of breast cancer remains uninvestigated. METHODS: We observed an increase in NAT10 expression, both at mRNA level through the analysis of the Cancer Genome Atlas (TCGA) database and at the protein level of tumor tissues from breast cancer patients. We determined that a heightened expression of NAT10 served as a predictor of an unfavorable clinical outcome. By screening the Cancer Cell Line Encyclopedia (CCLE) cell bank, this expression pattern of NAT10 was consistency found across almost all the classic breast cancer cell lines. RESULTS: Functionally, interference of NAT10 expression exerts an inhibitory effect on proliferation and invasion of breast cancer cells. By using ac4C RNA immunoprecipitation (ac4c-RIP) and acRIP-qPCR assays, we identified a reduction of ac4C enrichment within the ATP binding cassette (ABC) transporters, multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP), consequent to NAT10 suppression. Expressions of MDR1 and BCRP exhibited a positive correlation with NAT10 expression in tumor tissues, and the inhibition of NAT10 in breast cancer cells resulted in a decrease of MDR1 and BCRP expression. Therefore, the overexpressing of MDR1 and BCRP could partially rescue the adverse consequences of NAT10 depletion. In addition, we found that, remodelin, a NAT10 inhibitor, reinstated the susceptibility of capecitabine-resistant breast cancer cells to the chemotherapy, both in vitro and in vivo. CONCLUSION: The results of our study demonstrated the essential role of NAT10-mediated ac4c-modification in breast cancer progression and provide a novel strategy for overcoming chemoresistance challenges.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Neoplasias da Mama , Citidina , Feminino , Humanos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/patologia , Citidina/análogos & derivados , Acetiltransferases N-Terminal/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Mensageiro/genética
8.
Sci China Life Sci ; 67(7): 1398-1412, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38602587

RESUMO

Tumor cells establish a robust self-defense system characterized by hypoxia, antioxidant overexpression, DNA damage repair, and so forth to resist radiotherapy. Targeting one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under radiotherapy. Therefore, we herein developed an engineering biomimetic nanosystem (M@HHPt) masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens (O2) and cisplatin prodrugs (Pt(IV)) to target multiple tumor radioresistance hallmarks for enhanced radiotherapy. After administration, M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O2 and Pt(IV). O2 introduction induced hypoxia alleviation cooperated with Pt(IV) reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative stress. Moreover, the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA fragments. Consequently, M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%. Overall, this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.


Assuntos
Cisplatino , Nanopartículas , Tolerância a Radiação , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Linhagem Celular Tumoral , Animais , Tolerância a Radiação/efeitos dos fármacos , Nanopartículas/química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Pró-Fármacos/química , Radiossensibilizantes/farmacologia , Biomimética , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Oxigênio/metabolismo , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Reparo do DNA/efeitos dos fármacos , Antineoplásicos/farmacologia , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Proliferação de Células/efeitos dos fármacos
9.
Adv Healthc Mater ; : e2400406, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683036

RESUMO

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy.

10.
Cancer Res ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635903

RESUMO

Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single-cell RNA-sequencing in patients with newly diagnosed DLBCL. The CD58 mutation rate was 9.1%, and the copy number loss rate was 44.7% among all enrolled DLBCL patients. Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free and overall survival. Single-cell RNA sequencing revealed that CD58 expression in tumor cells was negatively correlated with CD8+ T cell exhaustion/dysfunction status. Insufficient T-cell activation resulting from CD58 alterations could not be attributed solely to CD2 signaling. CD58 inhibited the activity of the JAK2/STAT1 pathway by activating the Lyn/CD22/SHP1 axis, thereby limiting PD-L1 and IDO expression. Elevated PD-L1 and IDO expression in CD58 deficient DLBCL cells led to immune evasion and tumor-intrinsic resistance to CAR T-cell therapy. Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PD-L1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to CAR T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL.

11.
J Biomater Appl ; 38(3): 455-467, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37610341

RESUMO

A major obstacle to bone tissue repair is the difficulty in establishing a rapid blood supply areas of bone defects. Vascular endothelial growth factor (VEGF)-infused tissue-engineered scaffolds offer a possible therapeutic option for these types of injuries. Their role is to accelerate angiogenesis and improve bone healing. In this study, we used electrostatic spinning and biofactor binding to construct polylactic acid (PLA)/hydroxyapatite (HA)-VEGF scaffold materials and clarify their pro-vascular role in bone defect areas for efficient bone defect repair. PLA/HA nanocomposite fibrous membranes were manufactured by selecting suitable electrostatic spinning parameters. Heparin and VEGF were bound sequentially, and then the VEGF binding and release curves of the fiber membranes were calculated. A rat cranial defect model was constructed, and PLA/HA fiber membranes bound with VEGF and unbound with VEGF were placed for treatment. Finally, we compared bone volume recovery and vascular recovery in different fibrous membrane sites. A VEGF concentration of 2.5 µg/mL achieved the maximum binding and uniform distribution of PLA/HA fibrous membranes. Extended-release experiments showed that VEGF release essentially peaked at 14 days. In vivo studies showed that PLA/HA fibrous membranes bound with VEGF significantly increased the number of vessels at the site of cranial defects, bone mineral density, bone mineral content, bone bulk density, trabecular separation, trabecular thickness, and the number of trabeculae at the site of defects in rats compared with PLA/HA fibrous membranes not bound with VEGF. VEGF-bound PLA/HA fibrous membranes demonstrate the slow release of VEGF. The VEGF binding process does not disrupt the morphology and structure of the fibrous membranes. The fibrous membranes could stimulate both osteogenesis and angiogenesis. Taken together, this research provides a new strategy for critical-sized bone defects repairing.


Assuntos
Nanocompostos , Fator A de Crescimento do Endotélio Vascular , Animais , Ratos , Densidade Óssea , Durapatita , Poliésteres
12.
Oncol Rep ; 50(2)2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37387445

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Fig. 3A on p. 3399 were strikingly similar to data that were already under consideration for publication in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 40: 3392­3404, 2018; DOI: 10.3892/or.2018.6736].

13.
Front Cell Infect Microbiol ; 13: 1135013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868346

RESUMO

Cryo-electron tomography (cryo-ET) plays a critical role in imaging microorganisms in situ in terms of further analyzing the working mechanisms of viruses and drug exploitation, among others. A data processing workflow for cryo-ET has been developed to reconstruct three-dimensional density maps and further build atomic models from a tilt series of two-dimensional projections. Low signal-to-noise ratio (SNR) and missing wedge are two major factors that make the reconstruction procedure challenging. Because only few near-atomic resolution structures have been reconstructed in cryo-ET, there is still much room to design new approaches to improve universal reconstruction resolutions. This review summarizes classical mathematical models and deep learning methods among general reconstruction steps. Moreover, we also discuss current limitations and prospects. This review can provide software and methods for each step of the entire procedure from tilt series by cryo-ET to 3D atomic structures. In addition, it can also help more experts in various fields comprehend a recent research trend in cryo-ET. Furthermore, we hope that more researchers can collaborate in developing computational methods and mathematical models for high-resolution three-dimensional structures from cryo-ET datasets.


Assuntos
Tomografia com Microscopia Eletrônica , Vírus , Tomografia com Microscopia Eletrônica/métodos , Microscopia Crioeletrônica/métodos , Software , Fluxo de Trabalho , Processamento de Imagem Assistida por Computador/métodos
14.
Antioxidants (Basel) ; 12(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36830047

RESUMO

Itaconate has emerged as a novel anti-inflammatory and antioxidative endogenous metabolite, yet its role in allergic airway inflammation (AAI) and the underlying mechanism remains elusive. Here, the itaconate level in the lung was assessed by High Performance Liquid Chromatography (HPLC), and the effects of the Irg1/itaconate pathway on AAI and alveolar macrophage (AM) immune responses were evaluated using an ovalbumin (OVA)-induced AAI model established by wild type (WT) and Irg1-/- mice, while the mechanism of this process was investigated by metabolomics analysis, mitochondrial/cytosolic protein fractionation and transmission electron microscopy in the lung tissues. The results demonstrated that the Irg1 mRNA/protein expression and itaconate production in the lung were significantly induced by OVA. Itaconate ameliorated while Irg1 deficiency augmented AAI, and this may be attributed to the fact that itaconate suppressed mitochondrial events such as NLRP3 inflammasome activation, oxidative stress and metabolic dysfunction. Furthermore, we identified that the Irg1/itaconate pathway impacted the NLRP3 inflammasome activation and oxidative stress in AMs. Collectively, our findings provide evidence for the first time, supporting the conclusion that in the allergic lung, the itaconate level is markedly increased, which directly regulates AMs' immune responses. We therefore propose that the Irg1/itaconate pathway in AMs is a potential anti-inflammatory and anti-oxidative therapeutic target for AAI.

15.
Free Radic Biol Med ; 200: 102-116, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36907255

RESUMO

As a pattern recognition receptor which activates innate immune system, toll-like receptor 2 (TLR2) has been reportedly mediates allergic airway inflammation (AAI), yet the underlying mechanism remains elusive. Here, in a murine AAI model, TLR2-/- mice showed decreased airway inflammation, pyroptosis and oxidative stress. RNA-sequencing revealed that allergen-induced hif1 signaling pathway and glycolysis were significantly downregulated when TLR2 was deficient, which were confirmed by lung protein immunoblots. Glycolysis inhibitor 2-Deoxy-d-glucose (2-DG) inhibited allergen-induced airway inflammation, pyroptosis, oxidative stress and glycolysis in wild type (WT) mice, while hif1α stabilizer ethyl 3,4-dihydroxybenzoate (EDHB) restored theses allergen-induced changes in TLR2-/- mice, indicating TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in AAI. Moreover, upon allergen challenge, lung macrophages were highly activated in WT mice but were less activated in TLR2-/- mice, 2-DG replicated while EDHB reversed such effect of TLR2 deficiency on lung macrophages. Likewise, both in vivo and ex vivo WT alveolar macrophages (AMs) exhibited higher TLR2/hif1α expression, glycolysis and polarization activation in response to ovalbumin (OVA), which were all inhibited in TLR2-/- AMs, suggesting AMs activation and metabolic switch are dependent on TLR2. Finally, depletion of resident AMs in TLR2-/- mice abolished while transfer of TLR2-/- resident AMs to WT mice replicated the protective effect of TLR2 deficiency on AAI when administered before allergen challenge. Collectively, we suggested that loss of TLR2-hif1α-mediated glycolysis in resident AMs ameliorates allergic airway inflammation that inhibits pyroptosis and oxidative stress, therefore the TLR2-hif1α-glycolysis axis in resident AMs may be a novel therapeutic target for AAI.


Assuntos
Piroptose , Receptor 2 Toll-Like , Animais , Camundongos , Alérgenos , Inflamação/genética , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Hipersensibilidade Respiratória
16.
Acta Crystallogr C ; 68(Pt 9): o355-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22935503

RESUMO

Cocrystallization of melamine (1,3,5-triazine-2,4,6-triamine, ma) with (2-carboxyethyl)(phenyl)phosphinic acid (H(2)L) from water affords the title compound, C(3)H(7)N(6)(+)·C(9)H(10)O(4)P(-)·H(2)O or (maH)(HL)·H(2)O, (I). The phosphinic acid H atom of each H(2)L molecule is transferred to a melamine molecule. Structural analysis reveals that there are two types of secondary building units in the crystal structure, namely cationic [(maH(+))(2)](∞) ribbons and anionic {[(HL)(2)(H(2)O)(2)](2-)}(∞) layers, the combination of which through hydrogen-bond and electrostatic interactions, generates a large-scale two-dimensional layered structure. The thick layer is sandwich-like, with the central [(maH(+))(2)](∞) ribbons being further stabilized by π-π stacking interactions. It is also worthy of note that two conformational isomeric R(6)(5)(24) hydrogen-bond ring motifs can be identified in the {[(HL)(2)(H(2)O)(2)](2-)}(∞) layer.

17.
Environ Sci Pollut Res Int ; 29(19): 27636-27650, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34982386

RESUMO

Ecological environment of remote grassland has become a problem in many countries due to mining, tourism, grazing, and other human activities. In this study, a total of 15 pairs of soil-herbage samples were collected in the northeast of the Tibet Plateau to study the relationship between physicochemical properties and content of trace elements in soils at different elevation, and to examine the accumulation and fractionation of heavy metals in soil-herbage systems. In addition, the ecological risk of the subalpine grassland was also assessed. The average concentrations of Hg, As, Cu, Zn, Pb, Cd, Cr, and Mn in soil were higher than their background values of Gansu soil, but the average concentrations of these heavy metals in herbage satisfied Hygienical Standard for Feeds. The speciation analysis of heavy metals in soil indicated that the exchangeable content of heavy metal was very low, except Pb, Cd, and Mn. There was a linear relationship between pH, CaCO3, total phosphorus (TP), organic matter (OM), concentrations of Hg, As, Zn, Pb, Cr, and Mn in soils, dry weight of herbage, and elevation, while there was a quadratic curve trend between Cu, Cd in soils, and elevation. The results of risk assessment showed that there was no obvious ecological risk in the study area.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Oligoelementos , Cádmio/análise , China , Monitoramento Ambiental , Pradaria , Humanos , Chumbo/análise , Mercúrio/análise , Metais Pesados/análise , Medição de Risco , Solo/química , Poluentes do Solo/análise , Tibet , Oligoelementos/análise
18.
Environ Sci Pollut Res Int ; 29(27): 41081-41092, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35083690

RESUMO

Soil cadmium (Cd) and pyrene (PYR) pollutions have gained worldwide attention due to their negative effects on the environment. Intermittent flooding in rain-rich areas may affect phytoremediation of Cd and PYR in soil. Therefore, a pot-culture experiment, with and without flooding, was conducted to study the effects of flooding on soil Cd and PYR phytoremediation. Concentrations of Cd, PYR, and nutrients in soils and plants, as well as plant physiological and biochemical responses, were examined. Under both flooding and non-flooding conditions, willow (Salix × aureo-pendula CL 'J1011') demonstrated a better ability to remove soil Cd and PYR. Flooding led to higher Cd accumulation in roots than that in shoots. Conversely, non-flooding resulted in higher Cd accumulation in shoots than that in roots. The maximum concentrations of Cd in shoots were 11.02 and 14.07 mg kg-1 with and without flooding, respectively. The maximum dissipation rates of PYR in soil were 47.35% and 88.61% under flooding and non-flooding conditions, respectively. In addition, flooding significantly increased the photosynthetic pigment, photosynthetic fluorescence, and chlorophyll fluorescence parameters in leaves, compared with non-flooding treatment. Flooding also increased the concentrations of Mg, Mn, P, Fe, and K in roots and shoots. This study outlines an effective insight for the phytoremediation of Cd- and PYR-contaminated soil under flooding condition.


Assuntos
Salix , Poluentes do Solo , Biodegradação Ambiental , Cádmio/análise , Raízes de Plantas/química , Pirenos , Solo , Poluentes do Solo/análise
19.
J Environ Sci (China) ; 23(8): 1368-74, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22128545

RESUMO

A pot experiment was conducted to study the bioaccumulation and translocation of cadmium (Cd) in cole (Brassica campestris L.) and celery (Apium graveolens) grown in the Cd-polluted oasis soil, Northwest of China. The results showed that Cd in the unpolluted oasis soil was mainly bound to carbonate fraction (F2) and Fe-Mn oxide fraction (F3). However, marked change of Cd fractions was observed with increasing soil Cd concentrations, in which the concentration of Cd in Fl (exchangeable fraction), F2 and F3 increased significantly (p < 0.001 for Fl, F2 and F3). The growth of cole and celery could be facilitated by low concentrations of Cd, but inhibited by high concentrations. The correlation analysis between the fraction distribution coefficient of Cd in the soil and Cd concentration accumulated in the two vegetables showed that Cd in F1 in the soil made the greatest contribution on the accumulation of Cd in the two vegetables. The high bio-concentration factor and the translocation factor of Cd in both cole and celery were observed, and Cd had higher accumulation in the edible parts of the two vegetables. Therefore, both cole and celery grown in Cd-polluted oasis soil have higher risk to human health. And the two vegetables are not suitable to be cultivated as vegetables consumed by human in the Cd-polluted oasis soil.


Assuntos
Apium/metabolismo , Brassica/metabolismo , Cádmio/metabolismo , Poluentes do Solo/metabolismo , China
20.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33416073

RESUMO

Triple negative breast cancer (TNBC) is a more common type of breast cancer with high distant metastasis and poor prognosis. The potential role of lamins in cancer progression has been widely revealed. However, the function of lamin B2 (LMNB2) in TNBC progression is still unclear. The present study aimed to investigate the role of LMNB2 in TNBC. The cancer genome atlas (TCGA) database analysis and immunohistochemistry (IHC) were performed to examine LMNB2 expression levels. LMNB2 short hairpin RNA plasmid or lentivirus was used to deplete the expression of LMNB2 in human TNBC cell lines including MDA-MB-468 and MDA-MB-231. Alterations in cell proliferation and apoptosis in vitro and the nude mouse tumorigenicity assay in vivo were subsequently analyzed. The human TNBC tissues shown high expression of LMNB2 according to the bioinformation analysis and IHC assays. LMNB2 expression was correlated with the clinical pathological features of TNBC patients, including pTNM stage and lymph node metastasis. Through in vitro and in vivo assays, we confirmed LMNB2 depletion suppressed the proliferation and induced the apoptosis of TNBC cells, and inhibited tumor growth of TNBC cells in mice, with the decrease in Ki67 expression or the increase in caspase-3 expression. In conclusion, LMNB2 may promote TNBC progression and could serve as a potential therapeutic target for TNBC treatment.


Assuntos
Apoptose/fisiologia , Proliferação de Células/fisiologia , Lamina Tipo B/fisiologia , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Lamina Tipo B/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética
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