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1.
Cancer Sci ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676428

ABSTRACT

GLI1, a key transcription factor of the Hedgehog (Hh) signaling pathway, plays an important role in the development of cancer. However, the function and mechanisms by which GLI1 regulates gene transcription are not fully understood in gastric cancer (GC). Here, we found that GLI1 induced the proliferation and metastasis of GC cells, accompanied by transcriptional upregulation of INHBA. This increased INHBA expression exerted a promoting activity on Smads signaling and then transcriptionally activated GLI1 expression. Notably, our results demonstrate that disrupting the interaction between GLI1 and INHBA could inhibit GC tumorigenesis in vivo. More intriguingly, we confirmed the N6-methyladenosine (m6A) activation mechanism of the Helicobacter pylori/FTO/YTHDF2/GLI1 pathway in GC cells. In conclusion, our study confirmed that the GLI1/INHBA positive feedback loop influences GC progression and revealed the mechanism by which H. pylori upregulates GLI1 expression through m6A modification. This positive GLI1/INHBA feedback loop suggests a novel noncanonical mechanism of GLI1 activity in GC and provides potential therapeutic targets for GC treatment.

2.
Arch Toxicol ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602537

ABSTRACT

Gastrointestinal cancer is a significant global health burden, necessitating the development of novel therapeutic strategies. Emerging evidence has highlighted the potential of targeting ferritinophagy as a promising approach for the treatment of gastrointestinal cancer. Ferritinophagy is a form of selective autophagy that is mediated by the nuclear receptor coactivator 4 (NCOA4). This process plays a crucial role in regulating cellular iron homeostasis and has been implicated in various pathological conditions, including cancer. This review discusses the molecular mechanisms underlying ferritinophagy and its relevance to gastrointestinal cancer. Furthermore, we highlight the potential therapeutic implications of targeting ferritinophagy in gastrointestinal cancer. Several approaches have been proposed to modulate ferritinophagy, including small molecule inhibitors and immunotherapeutic strategies. We discuss the advantages and challenges associated with these therapeutic interventions and provide insights into their potential clinical applications.

3.
Adv Mater ; : e2313853, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684169

ABSTRACT

Organic acid-based deep eutectic solvents (DESs) as catalysts always suffer from weak stability and low recyclability due to the accumulation of organic oxidative products in the DES phase. Herein, a completely inorganic deep eutectic solvent (IDES) ZnCl2/PA with zinc chloride (ZnCl2) and phosphoric acid (PA) as precursors is constructed to realize liquid-liquid interface catalysis for desulfurization of fuel and product self-separation for the first time. Owing to the inorganic nature, the organic oxidative products are accumulated at the interface between the IDES and fuel rather than the IDES phase. With this unique feature, the IDES can be reused for at least 15 times without any further treatment in oxidative desulfurization process, showing a state-of-the-art cycle-regeneration stability. Moreover, compared with the reported organic DESs, the IDES also reveals more attractive catalytic oxidative desulfurization performance. Experimental and theoretical studies indicate that the strong coordination Zn···O═P and the strong adsorption energy between IDES and sulfides enhance the activation of H2O2 to reactive oxygen species, leading to the superior catalytic performance in oxidative desulfurization of fuel.

4.
Biomed Pharmacother ; 174: 116574, 2024 May.
Article in English | MEDLINE | ID: mdl-38593706

ABSTRACT

Gastrointestinal (GI) cancer is one of the most severe types of cancer, with a significant impact on human health worldwide. Due to the urgent demand for more effective therapeutic strategies against GI cancers, novel research on metal ions for treating GI cancers has attracted increasing attention. Currently, with accumulating research on the relationship between metal ions and cancer therapy, several metal ions have been discovered to induce cell death. In particular, the three novel modes of cell death, including ferroptosis, cuproptosis, and calcicoptosis, have become focal points of research in the field of cancer. Meanwhile, other metal ions have also been found to trigger cell death through various mechanisms. Accordingly, this review focuses on the mechanisms of metal ion-induced cell death in GI cancers, hoping to provide theoretical support for further GI cancer therapies.


Subject(s)
Cell Death , Gastrointestinal Neoplasms , Metals , Humans , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/drug therapy , Animals , Cell Death/drug effects , Ferroptosis/drug effects , Ions/metabolism , Antineoplastic Agents/pharmacology
5.
Adv Sci (Weinh) ; 11(18): e2401996, 2024 May.
Article in English | MEDLINE | ID: mdl-38482957

ABSTRACT

Porous Ionic Liquids (PILs) have gained attention but facing challenges in catalysis, especially in liquid-liquid two-phase reactions due to limited catalytic sites and hydrophilicity control. This work engineered a Type III PILs (PILS-M) using zeolitic imidazolate framework-8 (ZIF-8) confined phosphomolybdic acid (HPMo) as the microporous framework and N-butyl pyridine bis(trifluoromethane sulfonyl) imide ionic liquid ([Bpy][NTf2]) as the solvent. The PILS-M not only combines the advantages of traditional ionic liquids and microporous frameworks, including excellent extraction, high dispersion of catalytically active species, remarkable stability, etc., but also can make the inner surface of ZIF-8 turned to be hydrophilic that favors the contact between aqueous hydrogen peroxide oxidant and catalytically active sites for the promotion of catalytic performance in reactive extractive desulfurization (REDS) processes of fuel oils. This study demonstrates Type III PILs' potential as catalysts for sustainable chemical processes, offering insights into versatile PILs applications in diverse fields.

6.
J Agric Food Chem ; 72(12): 6178-6188, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38483540

ABSTRACT

Ferroptosis holds great potential as a therapeutic approach for gastric cancer (GC), a prevalent and deadly malignant tumor associated with high rates of incidence and mortality. Myricetin, well-known for its multifaceted biomedical attributes, particularly its anticancer properties, has yet to be thoroughly investigated regarding its involvement in ferroptosis. The aim of this research was to elucidate the impact of myricetin on ferroptosis in GC progression. The present study observed that myricetin could trigger ferroptosis in GC cells by enhancing malondialdehyde production and Fe2+ accumulation while suppressing glutathione levels. Mechanistically, myricetin directly interacted with NADPH oxidase 4 (NOX4), influencing its stability by inhibiting its ubiquitin degradation. Moreover, myricetin regulated the inhibition of ferroptosis induced by Helicobacter pylori cytotoxin-associated gene A (CagA) through the NOX4/NRF2/GPX4 pathway. In vivo experiments demonstrated that myricetin treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice. It was accompanied by increased NOX4 expression in tumor tissue and suppression of the NRF2/GPX4 antioxidant pathway. Therefore, this research underscores myricetin as a novel inducer of ferroptosis in GC cells through its interaction with NOX4. It is a promising candidate for GC treatment.


Subject(s)
Ferroptosis , Flavonoids , Stomach Neoplasms , Animals , Mice , NADPH Oxidase 4 , Mice, Nude , NF-E2-Related Factor 2
7.
J Colloid Interface Sci ; 662: 160-170, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38340515

ABSTRACT

Developing a highly efficient strategy for the stabilization of the solid-liquid interface is a persistent pursuit for researchers. Herein, porous ionic liquids based on UiO-66 (Zr) porous materials were synthesized and applied to the selective desulfurization catalysis, which integrates the permanent pores of porous solids with the exceptional properties of ionic liquids. Results show that porous ionic liquids possess high activity and selectivity for dibenzothiophene. Experimental analysis and density functional theory calculations revealed that the ionic liquids moiety served as an extractant to enrich dibenzothiophene into the porous ionic liquids phase through the π···π and CH···π interactions. Additionally, the electrostatic solvent effect in the porous ionic liquids contributes to the stabilization solid-liquid interface, which was favorable for UiO-66 moiety to catalytically activate hydrogen peroxide (H2O2) to generate ·OH radicals, and subsequently oxidized dibenzothiophene to the corresponding sulfone. It is hoped that the development of porous ionic liquids could pave a new route to the stabilization of the solid-liquid interface for catalytic oxidation.

8.
Inorg Chem ; 63(2): 1488-1498, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38175157

ABSTRACT

The crystal plane effect has gained extensive attention in heterogeneous catalysis reactions; however, it is far from being systematically probed in titanium dioxide (TiO2)-supported vanadium catalysts. Herein, a series of vanadium (V) single atoms and clusters anchored on TiO2 with different crystal planes was fabricated by an improved "top-down" protocol. The dispersion state, electronic structure, and redox properties of the V single-atom and VOx cluster-supported catalysts were systematically analyzed by a series of characterization methods, including X-ray absorption near edge structure (XANES) and density functional theory (DFT) calculations, and their catalytic performances were examined for aerobic oxidative desulfurization (AODS) of 4,6-dimethyl-dibenzothiophen (4,6-DMDBT) with O2 as the oxidant. The results unveiled that the synergistic effect between the V single atom and the VOx cluster perceptibly promoted the catalytic performances of VOx/TiO2 samples. Therein, VOx/TiO2-(001) shows the lowest apparent activation energy (Ea) value of 46.3 kJ/mol and the optimal AODS performance with complete 4,6-DMDBT conversion to 4,6-dimethyldibenzothiophene sulfone (4,6-DMDBTO2) within 60 min at 120 °C as compared with VOx/TiO2-(101) (81.9 kJ/mol and 180 min) and VOx/TiO2-(100) (68.0 kJ/mol and 240 min), which should be attributed to its higher V5+/V4+ ratio, the optimal redox behavior of the V species, the moderate adsorption energy between 4,6-DMDBT and VOx active centers, and the synthetic effect of V single atoms and VOx clusters. Moreover, VOx/TiO2-(001) exhibits robust durability in seven cycles of reuse, showcasing the potential for practical applications in the future.

9.
Inorg Chem ; 62(49): 20050-20061, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-37989485

ABSTRACT

In this contribution, we rationally designed and controllably fabricated a NiMo/Al2O3-montmorillonite (3D-NiMo/Al2O3-MMT) monolithic catalyst via a 3D printing strategy with economical montmorillonite (MMT) as a binder. The catalytic performance of the resulting NiMo/Al2O3-MMT for 4,6-dimethyldibenzothiophene (4,6-DMDBT) hydrodesulfurization (HDS) was evaluated. The experimental results unveil that the 3D-NiMo/Al2O3-MMT monolithic catalyst exhibits robust stability and exceptional HDS activity with 99.2% 4,6-DMDBT conversion (residual 4 ppm of S), which is remarkably superior to that of conventional NiMo/Al2O3 (61.5%), NiMo/MMT (63.2%), and even NiMo/Al2O3-MMT (76.5%) prepared by the mechanical-mixing method. This should be ascribed to the synthetic effect between the MMT binder and the Al2O3 substrate, which effectively weakens the interaction between the Mo species and the Lewis acids on the original Al2O3 surface, thereby significantly increasing the content of reducible Mo species and considerably facilitating the formation of more highly active NiMoS phase (Type II) with optimal average stacking layers and thereafter remarkably enhancing the ultradeep HDS activity of the 3D-NiMo/Al2O3-MMT monolithic catalyst.

10.
Chem Commun (Camb) ; 59(80): 12031-12034, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37728438

ABSTRACT

Two isostructural hydrogen-bonded organic frameworks (HOFs) with 1-D hexagonal-shaped pores were crystallised using the molecules biphenyl-3,3',5,5'-tetracarboxylic acid (BPTCA) and [1,1':4',1'']terphenyl- 3,3'',5,5''-tetracarboxylic acid (TPTCA). The desolvated HOFs, named BPTCA-2 and TPTCA-2, exhibited selective adsorption towards naphthalene and anthracene, respectively, during competitive adsorption experiments.

11.
Inorg Chem ; 62(28): 11044-11055, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37414580

ABSTRACT

The design and preparation of catalysts with both excellent stability and maximum exposure of catalytic active sites is highly desirable; however, it remains challenging in heterogeneous catalysis. Herein, a entropy-stabilized single-site Mo catalyst via a high-entropy perovskite oxide LaMn0.2Fe0.2Co0.2Ni0.2Cu0.2O3 (HEPO) with abundant mesoporous structures was initiated by a sacrificial-template strategy. The presence of electrostatic interaction between graphene oxide and metal precursors effectively inhibits the agglomeration of precursor nanoparticles in a high-temperature calcination process, thereby endowing the atomically dispersed Mo6+ coordinated with four O atoms on the defective sites of HEPO. The unique structure of single-site Mo atoms' random distribution with an atomic scale greatly enriches the oxygen vacancy and increases surface exposure of the catalytic active sites on the Mo/HEPO-SAC catalyst. As a result, the obtained Mo/HEPO-SAC exhibits robust recycling stability and ultra-high oxidation activity (turnover frequency = 3.28 × 10-2) for the catalytic removal of dibenzothiophene (DBT) with air as the oxidant, which represents the top level and is strikingly higher than the state-of-the-art oxidation desulfurization catalysts reported previously under the same or similar reaction conditions. Therefore, the finding here for the first time expands the application of single-atom Mo-supported HEPO materials into the field of ultra-deep oxidative desulfurization.

12.
ACS Appl Mater Interfaces ; 15(28): 33593-33604, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37431547

ABSTRACT

The development of a competitive-cost and high-efficiency NiMo/Al2O3 hydrodesulfurization (HDS) catalyst remains challenging in the field of petrochemical industry. Herein, a highly efficient NiMo/Al2O3 monolithic HDS catalyst was elaborately designed and successfully fabricated via a one-pot three-dimensional (3D) printing strategy, and its HDS activity was examined for 4,6-dimethyldibenzothiophene conversion. The results unveil that the NiMo/Al2O3 monolithic catalyst prepared by the 3D printing strategy (3D-NiMo/Al2O3) exhibits hierarchical structure due to the combustion of hydroxymethyl cellulose serving as adhesive, which endows the weaker metal-support-interaction between Mo oxides and Al2O3, remarkably promoting sulfidation of both Mo and Ni species and the formation of "Type II" NiMoS active phase, thereby reducing the apparent activation energy (Ea = 109.2 kJ·mol-1) and increasing the catalytic activity (TOF = 4.0 h-1) and thereafter dramatically boosting the HDS performance of 3D-NiMo/Al2O3 compared with that of NiMo/Al2O3 (Ea = 150.6 kJ·mol-1 and TOF = 2.1 h-1) counterpart synthesized by conventional method with P123 serving as the mesoporous template. Therefore, this study offers a facile and straightforward strategy to fabricate an efficient HDS catalyst with hierarchical structures.

13.
Inorg Chem ; 62(23): 9199-9208, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37229753

ABSTRACT

Developing catalysts with optimized surface properties is significant for advanced catalysis. Herein, a rational architectural design is proposed to successfully synthesize yolk-shell nickel molybdate with abundant oxygen vacancies (YS-VO-NMO) via an acid-assisted defect engineering strategy. Notably, YS-VO-NMO with the yolk-shell structure shows complex nanoconfined interior space, which is beneficial to the mass transfer and active sites exposure. Moreover, the defect engineering strategy is of great importance to modulate the surface electronic structure and atomic composition, which contributes to the enrichment of oxygen vacancies. Benefiting from these features, the higher hydrogen peroxide activation is achieved by YS-VO-NMO to produce more hydroxyl radicals compared with untreated nickel molybdate. Consequently, the defect-engineered YS-VO-NMO not only features superior catalytic activity (99.5%) but also retains high desulfurization efficiency after recycling eight times. This manuscript provides new inspiration for designing more promising defective materials via defect engineering and architecture for different applications besides oxidative desulfurization.

14.
BMC Med ; 21(1): 134, 2023 04 05.
Article in English | MEDLINE | ID: mdl-37016382

ABSTRACT

BACKGROUND: Helicobacter pylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. METHODS: The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. RESULTS: GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746-179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo-YAP1 pathway in both in vitro and in vivo models. CONCLUSIONS: Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.


Subject(s)
GTP-Binding Protein beta Subunits , Helicobacter pylori , Stomach Neoplasms , Humans , Mice , Animals , NF-kappa B/genetics , NF-kappa B/metabolism , Helicobacter pylori/metabolism , Mice, Nude , Carcinogenesis/genetics , Stomach Neoplasms/genetics , Demethylation , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Mixed Function Oxygenases/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , GTP-Binding Protein beta Subunits/genetics , GTP-Binding Protein beta Subunits/metabolism
15.
Inorg Chem ; 62(14): 5780-5790, 2023 Apr 10.
Article in English | MEDLINE | ID: mdl-36976898

ABSTRACT

Achieving long-term stable deep desulfurization at room temperature and recovering high value-added sulfone products is a challenge at present. Herein, a series of catalysts [Cnmim]5VW12O40Br (CnVW12, 1-alkyl-3-methylimidazolium bromide tungstovanadate, n = 4, 8, 16) were presented for the room temperature catalytic oxidation of dibenzothiophene (DBT) and its derivatives. Factors affecting the reaction process, such as the amount of catalyst, oxidant, and temperature, were systematically discussed. C16VW12 showed higher catalytic performance, and 100% conversion and selectivity could be achieved in 50 min with only 10 mg. The mechanism study showed that the hydroxyl radical was the active radical in the reaction. Benefiting from the "polarity strategy", the sulfone product accumulated after 23 cycles in a C16VW12 system, and the yield and purity were about 84% and 100%, respectively.

16.
J Colloid Interface Sci ; 641: 289-298, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36934576

ABSTRACT

Bimetallic oxide is a potential catalyst for oxidative desulfurization of fuel. Thus, an appropriate method is needed to improve its catalytic performance. Manufacturing defect is an effective means. In this contribution, an oxygen vacancies (OVs) regulation strategy for enhancing the catalytic activity of bimetallic oxide is proposed. Density functional theory (DFT) calculations show that the crystal phase has a huge influence on the generation energy of oxygen vacancies, so a series of V-Nb mixed oxide with different crystal phases are synthesized. Detailed characterizations show that the as-prepared tetragonal V-Nb mixed oxide (T-VNbOx) has lower OVs formation energy and larger OVs concentration (compared to orthorhombic V-Nb mixed oxides, O-VNbOx). Owing to the activation of OVs, the catalytic activity of T-VNbOx was significantly enhanced to form ultra-deep oxidative desulfurization. In addition, T-VNbOx can be cycled eight times without significantly degrading the desulfurization performance.

17.
Arch Biochem Biophys ; 740: 109560, 2023 05 15.
Article in English | MEDLINE | ID: mdl-36948350

ABSTRACT

Ferroptosis is a newly discovered form of regulatory cell death induced by iron-dependent lipid peroxidation. Infection with Helicobacter pylori (H. pylori) is regarded as a high-risk factor for the development of gastric cancer (GC) and is associated with an increase in the levels of reactive oxygen species with activation of oncogenic signaling pathways. However, whether GC arising in the context of infection with H. pylori is correlated with ferroptosis is still unknown. In this study, we demonstrate that H. pylori infection increased the sensitivity of GC cells to RSL3 (RAS-selective lethal3)-induced ferroptosis. The molecular subtypes mediated by ferroptosis-related genes are associated with tumor microenvironment (TME) cell infiltration and patient survival. Importantly, we identified that the expression of phosphorylase kinase G2 (PHKG2) was remarkably correlated with H. pylori infection, metabolic biological processes, patient survival and therapy response. We further found the mechanism of H. pylori-induced cell sensitivity to ferroptosis, which involves PHKG2 regulation of the lipoxygenase enzyme Arachidonate 5-Lipoxygenase (ALOX5). In conclusion, PHKG2 facilitates RSL3-induced ferroptosis in H. pylori-positive GC cells by promoting ALOX5 expression. These findings may contribute to a better understanding of the unique pathogenesis of H. pylori-induced GC and allow for maximum efficacy of genetic, cellular, and immune therapies for controlling ferroptosis in diverse contexts.


Subject(s)
Ferroptosis , Helicobacter pylori , Stomach Neoplasms , Humans , Phosphorylase Kinase , Stomach Neoplasms/metabolism , Cell Death , Tumor Microenvironment
18.
mBio ; 14(1): e0266622, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36602309

ABSTRACT

Cryptosporidium parvum has gained much attention as a major cause of diarrhea in the world, particularly in those with compromised immune systems. The data currently available on how the immune system recognizes C. parvum are growing rapidly, but we lack data on the interactions among host major histocompatibility complex (MHC) diversity and parasitic T-cell epitopes. To identify antigenic epitopes in a murine model, we performed systematic profiling of H-2Kb-restricted peptides by screening the dominant Cryptosporidium antigens. The results revealed that the glycoprotein-derived epitope Gp40/15-SVF9 induced an immunodominant response in C. parvum-recovered C57BL/6 mice, and injection of the cytotoxic-T-lymphocyte (CTL) peptide with the adjuvant activated peptide-specific CD8+ T cells. Notably, the SVF9 epitope was highly conserved across Cryptosporidium hominis, C. parvum, and many other Cryptosporidium species. SVF9 also formed stable peptide-MHC class I (MHC I) complexes with HLA-A*0201, suggesting cross-reactivity between H-2Kb and human MHC I specificities. Crystal structure analyses revealed that the interactions of peptide-MHC surface residues of H-2Kb and HLA-A*0201 are highly conserved. The hydrogen bonds of H-2Kb-SVF9 are similar to those of a dominant epitope presented by HLA-A*0201, which can be recognized by a public human T-cell receptor (TCR). Notably, we found double conformations in position 4 (P4), 5 (P5) of the SVF9 peptide, which showed high flexibility, and multiple peptide conformations generated more molecular surfaces that can potentially be recognized by TCRs. Our findings demonstrate that an immunodominant C. parvum epitope and its homologs from different Cryptosporidium species and subtypes can benefit vaccine development to combat cryptosporidiosis. IMPORTANCE Adaptive immune responses and T lymphocytes have been implicated as important mechanisms of parasite-induced protection. However, the role of CD8+ T lymphocytes in the resolution of C. parvum infection is largely unresolved. Our results revealed that the glycoprotein-derived epitope Gp40/15-SVF9 induced an immunodominant CD8+ T-cell response in C57BL/6 mice. Crystal structure analyses revealed that the interactions of the H-2Kb-SVF9 peptide are similar to those of a dominant epitope presented by HLA-A*0201, which can be recognized by human TCRs. In addition, we found double conformations of the SVF9 peptide, which showed high flexibility and multiple peptide conformations that can potentially be recognized by TCRs.


Subject(s)
Cryptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Mice , Humans , Animals , CD8-Positive T-Lymphocytes , Mice, Inbred C57BL , T-Lymphocytes, Cytotoxic , Peptides , Immunodominant Epitopes , Epitopes, T-Lymphocyte , Receptors, Antigen, T-Cell , Glycoproteins
19.
Cancer Biother Radiopharm ; 38(9): 585-595, 2023 Nov.
Article in English | MEDLINE | ID: mdl-33351694

ABSTRACT

Background: Osteosarcoma (OS) is a common, aggressive primary sarcoma of bone. Drug resistance is a huge obstacle to chemotherapy for cancer. This study aimed to investigate the role and mechanism of circ_0002060 in OS resistance to doxorubicin (DOX). Methods: The levels of circ_0002060, miR-198, and ATP-binding cassette subfamily B member 1 (ABCB1) in OS tissues and DOX-resistant OS cells were measured by quantitative real-time polymerase chain reaction or Western blot assay. Kaplan-Meier analysis was performed to determine the relationship between circ_0002060 expression in OS tissues and overall survival of OS patients. The half-inhibitory concentration (IC50) of DOX was calculated using the Cell Counting Kit-8 (CCK-8) assay. Proliferation and apoptosis of DOX-resistant OS cells were assessed by colony formation assay and flow cytometry. The levels of apoptosis-related proteins in DOX-resistant OS cells were measured by Western blot assay. Xenograft assay was utilized to analyze the effect of circ_0002060 on DOX resistance in vivo. The interactions among circ_0002060, miR-198, and ABCB1 in DOX-resistant OS cells were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay, or RNA pull-down assay. Results: circ_0002060 and ABCB1 were upregulated, while miR-198 was downregulated in OS tissues and DOX-resistant OS cells. circ_0002060 silencing reduced DOX resistance in vitro and in vivo. Moreover, circ_0002060 enhanced DOX resistance by sponging miR-198. Besides, miR-198 decreased DOX resistance by binding to ABCB1. In addition, circ_0002060 sponged miR-198 to upregulate ABCB1 expression. Conclusions: circ_0002060 promoted DOX resistance and OS progression by regulating the miR-198/ABCB1 axis, suggesting that circ_0002060 might be a promising biomarker for OS therapy.


Subject(s)
Bone Neoplasms , MicroRNAs , Osteosarcoma , Humans , Apoptosis , ATP Binding Cassette Transporter, Subfamily B/genetics , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , MicroRNAs/genetics , Osteosarcoma/drug therapy , Osteosarcoma/genetics , RNA, Circular/genetics
20.
J Colloid Interface Sci ; 629(Pt B): 569-580, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36179577

ABSTRACT

High entropy oxides are promising catalysts for numerous catalytic oxidation processes with oxygen as the oxidant. However, most of them often show bulk morphologies, which hinders the full exposure of active sites. In this work, a unique 26-faceted polyhedral high entropy oxide MnNiCuZnCoOx-1000 (P-HEO) with highly active site exposure is fabricated via a mechanochemistry-assisted strategy. By employing such a strategy, the supersaturation of P-HEO during the crystal growth process is effectively reduced to form high-index facets, which is proved to be beneficial to the formation of high-index facets. Characterization results indicate that more oxygen vacancies are generated in P-HEO compared with the bulk counterparts. Density functional theory calculations reveal that the high-index facets {-211} can facilitate adsorption and activation of O2 because of the higher adsorption energy -2.23 eV compared with that of (111) surfaces (-1.79 eV), which induces significantly enhanced activity for organic sulfides oxidation. Interestingly, the synthesized P-HEO with high-index facets shows a 98.4% removal rate of dibenzothiophene from model oil within 8 h at 120 °C, which is much higher than that of the bulk counterparts (33.5%).

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