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1.
Histopathology ; 84(7): 1199-1211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409885

RESUMO

AIMS: Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown. METHODS AND RESULTS: In this study, 47 patients were enrolled and their tumour specimens were analysed by whole-exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression-free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance. CONCLUSION: This study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.


Assuntos
Neoplasias Encefálicas , Sequenciamento do Exoma , Neoplasias Embrionárias de Células Germinativas , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Feminino , Adolescente , Criança , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Pré-Escolar , China/epidemiologia , Adulto , Adulto Jovem , Variações do Número de Cópias de DNA , Mutação , Povo Asiático/genética , Proteína Reelina , Biomarcadores Tumorais/genética , Prognóstico , População do Leste Asiático
2.
Acta Neurochir (Wien) ; 166(1): 72, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329556

RESUMO

PURPOSE: Medulloblastoma is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. Recent transcriptional studies have shown that medulloblastomas comprise at least four molecular subgroups, each with distinct demographics, genetics, and clinical outcomes. Medulloblastoma subtyping has become critical for subgroup-specific therapies. The use of gene expression assays to determine the molecular subgroup of clinical specimens is a long-awaited application of molecular biology for this pediatric cancer. METHODS: In the current study, we established a medulloblastoma transcriptome database of 460 samples retrieved from three published datasets (GSE21140, GSE37382, and GSE37418). With this database, we identified a 23-gene signature that is significantly associated with the medulloblastoma subgroups and achieved a classification accuracy of 95.2%. RESULTS: The 23-gene signature was further validated in a long-term cohort of 142 Chinese medulloblastoma patients. The 23-gene signature classified 21 patients as WNT (15%), 41 as SHH (29%), 16 as Group 3 (11%), and 64 as Group 4 (45%). For patients of WNT, SHH, Group 3, and Group 4, 5-year overall-survival rate reached 80%, 62%, 27%, and 47%, respectively (p < 0.0001), meanwhile 5-year progression-free survival reached 80%, 52%, 27%, and 45%, respectively (p < 0.0001). Besides, SHH/TP53-mutant tumors were associated with worse prognosis compared with SHH/TP53 wild-type tumors and other subgroups. We demonstrated that subgroup assignments by the 23-gene signature and Northcott's NanoString assay were highly comparable with a concordance rate of 96.4%. CONCLUSIONS: In conclusion, we present a novel gene signature that is capable of accurately and reliably assigning FFPE medulloblastoma samples to their molecular subgroup, which may serve as an auxiliary tool for medulloblastoma subtyping in the clinic. Future incorporation of this gene signature into prospective clinical trials is warranted to further evaluate its clinical.


Assuntos
Neoplasias Encefálicas , Neoplasias Cerebelares , Meduloblastoma , Humanos , Criança , Meduloblastoma/diagnóstico , Meduloblastoma/genética , Transcriptoma/genética , Estudos Prospectivos , Neoplasias Cerebelares/genética , China
3.
Angew Chem Int Ed Engl ; 63(6): e202318115, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38116913

RESUMO

The non-noble-metal catalysed-multicomponent reactions between flue gas CO2 and cheap industrial raw stocks into high value-added fine chemicals is a promising manner for the ideal CO2 utilization route. To achieve this, the key fundamental challenge is the rational development of highly efficient and facile reaction pathway while establishing compatible catalytic system. Herein, through the stepwise solvent-assisted linker installation, post-synthetic fluorination and metalation, we report the construction of a series of perfluoroalkyl-decorated noble-metal-free metal-organic frameworks (MOFs) PCN-(BPY-CuI)-(TPDC-Fx ) [BPY=2,2'-bipyridine-5,5'-dicarboxylate, TPDC-NH2 =2'-amino-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid] that can catalyze the one-pot four-component reaction between alkyne, aldehyde, amine and flue gas CO2 for the preparation of 2-oxazolidinones. Such assembly endows the MOFs with superhydrophobic microenvironment, superior water resistance and highly stable catalytic site, leading to 21 times higher turnover numbers than that of homogeneous counterparts. Mechanism investigation implied that the substrates can be efficiently enriched by the MOF wall and then the adsorbed amine species act as an extrinsic binding site towards dilute CO2 through their strong preferential formation to carbamate acid. Moreover, density functional theory calculations suggest the tetrahedral geometry of Cu in MOF offers special resistance towards amine poisoning, thus maintaining its high efficiency during the catalytic process.

4.
World J Clin Cases ; 11(29): 7179-7186, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37946772

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a chronic rheumatic disease that primarily affects the spine and the sacroiliac and peripheral joints. Juvenile-onset AS (JoAS) patients will likely present with peripheral joint symptoms. Knee flexion contracture (KFC) and hip flexion contracture (HFC) are common in these patients due to subchondral bone inflammation. The Ilizarov technique is the most commonly used technique for treating KFC. However, its use to treat JoAS-associated KFC has not been reported. CASE SUMMARY: This report presents a case study of a 31-year-old male patient with a squatting gait due to severe bilateral KFC and HFC. The patient had a normal walking pattern until the age of eight, after which he experienced knee and hip pain, leading to the gradual development of KFC and HFC. The patient's primary complaint was an inability to walk upright. The patient was diagnosed with JoAS and underwent hip dissection and release, limited soft tissue release of the hamstring, and gradual traction using the Ilizarov method. Ultimately, the patient was able to walk upright. CONCLUSION: The incidence of squatting gait due to KFC in individuals diagnosed with JoAS was low. Utilizing the Ilizarov technique has proven to be a secure and effective method for managing KFC in JoAS patients. Although the Ilizarov technique cannot substitute for total knee arthroplasty (TKA), its application can delay the need for primary TKA in JoAS patients and alleviate the intricacy and potential complications associated with the procedure.

5.
J Neurooncol ; 164(1): 127-139, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37462801

RESUMO

BACKGROUND: Glioma is the most malignant primary brain tumor with a poor survival time. The tumour microenvironment, especially glioma-associated microglia/macrophages (GAMs), plays an important role in the pathogenesis of glioma. Currently, microglia (CD11b+/CD45Low) and macrophages (CD11b+/CD45High) are distinguished as distinct cell types due to their different origins. Moreover, signal-transducing adaptor protein 1 (STAP1) plays a role in tumourigenesis and immune responses. However, to date, no studies have been reported on STAP1 in GAMs. METHODS: The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to investigate the association between STAP1 mRNA levels and clinical parameters (grades, mutations in isocitrate dehydrogenase, and overall survival). RNA-sequencing, qRT-PCR, Western blotting, immunohistochemistry and immunofluorescence analyses were performed to detect the expression level of STAP1 and related proteins. BV-2 cells were used to construct a STAP1-overexpressing cell line. Phagocytosis of BV-2 cells was assessed by flow cytometry and fluorescence microscopy. C57BL/6 mice were used to establish orthotopic and subcutaneous glioma mouse models. Glioma growth was monitored by bioluminescence imaging. RESULTS: STAP1 expression in glioma-associated microglia is positively correlated with the degree of malignancy and poor prognosis of glioma. Moreover, STAP1 may promote M2-like polarisation by increasing ARG1 expression and inhibiting microglial phagocytosis of microglia. Increased ARG1 may be associated with the IL-6/STAT3 pathway. Impaired phagocytosis may be associated with decreased cofilin and filopodia. CONCLUSION: STAP1 is positively associated with the degree of glioma malignancy and may represent a potential novel therapeutic target for glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Camundongos , Animais , Microglia , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Glioma/metabolismo , Macrófagos , Neoplasias Encefálicas/metabolismo , Microambiente Tumoral
6.
ACS Nano ; 17(10): 9126-9139, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37097811

RESUMO

Administration of bispecific antibodies (biAbs) in tumor therapy is limited by their short half-life and off-target toxicity. Optimized strategies or targets are needed to overcome these barriers. B7-H3 (CD276), a member of the B7 superfamily, is associated with poor survival in glioblastoma (GBM) patients. Moreover, a dimer of EGCG (dEGCG) synthesized in this work enhanced the IFN-γ-induced ferroptosis of tumor cells in vitro and in vivo. Herein, we prepared recombinant anti-B7-H3×CD3 biAbs and constructed MMP-2-sensitive S-biAb/dEGCG@NPs to offer a combination treatment strategy for efficient and systemic GBM elimination. Given their GBM targeted delivery and tumor microenvironment responsiveness, S-biAb/dEGCG@NPs displayed enhanced intracranial accumulation, 4.1-, 9.5-, and 12.3-fold higher than that of biAb/dEGCG@NPs, biAb/dEGCG complexes, and free biAbs, respectively. Furthermore, 50% of GBM-bearing mice in the S-biAb/dEGCG@NP group survived longer than 56 days. Overall, S-biAb/dEGCG@NPs can induce GBM elimination by boosting the ferroptosis effect and enhancing immune checkpoint blockade (ICB) immunotherapy and may be successful antibody nanocarriers for enhanced cancer therapy.


Assuntos
Anticorpos Biespecíficos , Ferroptose , Glioblastoma , Camundongos , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Glioblastoma/tratamento farmacológico , Metaloproteinase 2 da Matriz , Imunoterapia , Microambiente Tumoral
7.
J Colloid Interface Sci ; 637: 1-9, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36682113

RESUMO

Herein, the covalently connected core-shell metal-organic frameworks (MOFs)@covalent-organic frameworks (COFs) hybrid materials were successfully constructed by coating the stable COF-OH shell on the NH2-MIL-125 core. The introduction of the NH2-MIL-125 core endowed the hybrid materials with high Brunauer-Emmett-Teller (BET) surface area (SBET) and abundant unsaturated metal sites. And the coating of COF-OH shell endowed the hybrid materials outstanding physicochemical stability and visible-light response, and suitable band gaps. Moreover, the thickness of the COF-OH shell was carefully adjusted according to the feeding amount of NH2-MIL-125. Impressively, the electron transfer pathway in the formed heterostructure was clarified and it was proven that a type-II heterojunction was generated between the MOFs and the COFs. The formed stable CN covalent bonds in the interfacial layer was beneficial to the photogenerated electron transfer and the electron-hole pairs separation, which greatly enhanced the CO2 photocatalytic reduction. The product NH2-MIL-125@COF-3 exhibited the highest CO yield of 22.93 µmol·g-1·h-1, about 2 times higher than NH2-MIL-125 (11.82 µmol·g-1·h-1) and 3 times greater than COF-OH (7.26 µmol·g-1·h-1). This work can provide helpful ideas for the careful design of the novel MOFs@COFs hybrid materials as well as useful exploration for the CO2 photocatalytic reduction.

8.
J Cereb Blood Flow Metab ; 42(8): 1364-1382, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35484910

RESUMO

The recent discovery of the meningeal lymphatic vessels (mLVs) and glymphatic pathways has challenged the long-lasting dogma that the central nervous system (CNS) lacks a lymphatic system and therefore does not interact with peripheral immunity. This discovery has reshaped our understanding of mechanisms underlying CNS drainage. Under normal conditions, a close connection between mLVs and the glymphatic system enables metabolic waste removal, immune cell trafficking, and CNS immune surveillance. Dysfunction of the glymphatic-mLV system can lead to toxic protein accumulation in the brain, and it contributes to the development of a series of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. The identification of precise cerebral transport routes is based mainly on indirect, invasive imaging of animals, and the results cannot always be applied to humans. Here we review the functions of the glymphatic-mLV system and evidence for its involvement in some CNS diseases. We focus on emerging noninvasive imaging techniques to evaluate the human glymphatic-mLV system and their potential for preclinical diagnosis and prevention of neurodegenerative diseases. Potential strategies that target the glymphatic-mLV system in order to treat and prevent neurological disorders are also discussed.


Assuntos
Doenças do Sistema Nervoso Central , Sistema Glinfático , Animais , Encéfalo/metabolismo , Sistema Nervoso Central , Sistema Glinfático/metabolismo , Sistema Linfático
9.
J Hazard Mater ; 429: 128303, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35101759

RESUMO

In this paper, thioether-functionalized porphyrin-based polymers (TPPs) were constructed according to two different "bottom-up" and "top-down" strategies and they were applied for Hg2+ capture in aqueous solution. TPP1, which was constructed by one-step polycondensation of 2,5-bis(methylthio) terephthalaldehyde (BMTA) with pyrrole according to the "bottom-up" strategy, owned high Brunauer-Emmett-Teller (BET) surface area (SBET, 554 m2/g), pore volume (Vtotal, 0.32 cm3/g), and S content (16.8%), resulting in high Hg2+ capture (913 mg/g) with high removal efficiency (> 99%). The adsorption mechanism clarified that the strong coordination between the S species and Hg2+ was the main driving force. In comparison, TPP2 and TPP3 were fabricated by the thioether functionalization of the porphyrin-based polymers according to the "top-down" strategy. They showed much lower SBET, Vtotal, and S content for the reason that the post-functionalization process greatly blocked the pores and the functional sites were hardly fully post-functionalized, resulting in much lower Hg2+ capture (555 mg/g and 609 mg/g, respectively). This work reveals the advantage of the "bottom-up" strategy for the construction of the thioether-functionalized polymers and it offers the guidance for the construction of some other thioether-functionalized polymers.


Assuntos
Mercúrio , Porfirinas , Adsorção , Polímeros , Sulfetos
10.
Chemosphere ; 288(Pt 1): 132499, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34626649

RESUMO

Lignin is a natural O-containing aromatic amorphous polymers from the residues of biorefinery and industrial papermaking, it can derive lots of aromatic phenol chemicals used as industrial raw materials by an efficient depolymerization, and then produce synthetic polymers. Here, we selected six aromatic units from the liquid products of lignin depolymerization, and tried to prepare diversified O-rich hyper-cross-linked polymers (HCPs) by one-pot Friedel-Crafts alkylation reaction for CO2 and iodine vapor capture. HCP1, HCP2, and HCP3 microspheres possessed similar porous structure with Brunauer-Emmett-Teller (BET) surface areas (SBET) of 14.1-20.6 m2/g and high O content (26.34-30.68 wt%), while HCP4, HCP5, and HCP6 were composed of many bulks with 3D networks structure, and showed larger SBET of 15.4-246.9 m2/g and relatively low O content (18.48-26.38 wt%). The results indicated that the chemical position and quantities of substituent groups (methoxy and alkyl) into lignin-derived units had evident impact on their morphology and textural parameters. These HCPs exhibited considerable CO2 uptake (64.1 mg/g) and selectivity (35.2) at 273 K, and high iodine vapor uptake (192.3 wt%). Moreover, the performance analysis implied that the SBET and pore volume of these HCPs had not played the dominated roles in the CO2 and I2 adsorption, while their pore size distribution, O-functional groups, and electron density will be more important for the capture of the both. This study will offer a facile synthesis of O-rich polymer microsphere adsorbents based on the green and sustainable lignin.


Assuntos
Iodo , Lignina , Adsorção , Dióxido de Carbono , Microesferas , Oxigênio , Fenóis , Polímeros , Porosidade
11.
Mol Cancer ; 20(1): 168, 2021 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-34922552

RESUMO

BACKGROUND: Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown. METHODS: In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays. RESULTS: We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer ß-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation. CONCLUSIONS: Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of ß-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.


Assuntos
Craniofaringioma/genética , Mutação , Neoplasias Hipofisárias/genética , beta Catenina/genética , Biomarcadores Tumorais , Biologia Computacional/métodos , Craniofaringioma/diagnóstico , Humanos , Mutação INDEL , Neoplasias Hipofisárias/diagnóstico , Polimorfismo de Nucleotídeo Único , Prognóstico , Células Tumorais Cultivadas , Sequenciamento Completo do Genoma , Via de Sinalização Wnt
12.
Oncoimmunology ; 10(1): 1983306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595061

RESUMO

T cell-engaging therapies involving bispecific T cell engager (BiTE) and chimeric antigen receptor T (CAR-T) cells have achieved great success in the treatment of hematological tumors. However, the paucity of ideal cell surface molecules that can be targeted on glioblastoma (GBM) partially reduces the immunotherapeutic efficacy. Recently, high expression of Fn14 has been reported in several solid tumors, so the strategy of exploiting this specific antigen for GBM immunotherapy is worth studying. Consequently, we constructed Fn14× CD3 BiTE and Fn14-specific CAR-T cells and investigated their cytotoxic activity against GBM in vitro and in vivo. First, expression of Fn14 was confirmed in glioma tissues and GBM cells. Then, we designed Fn14-specific BiTE and CAR-T cells and tested their cytotoxicity in GBM cell cultures and mouse models of GBM. Fn14 was highly expressed in GBM tissues and cell lines, while it was undetectable in normal brain samples. Fn14× CD3 BiTE, Fn14 CAR-T cells and Fn14 CAR-T/IL-15 cells were antigen-specific and highly cytotoxic, showing good antitumor activity in vitro and causing significant regression of established solid tumors in xenograft models. However, the xenografts treated with Fn14 CAR-T cells regrew, whereas xenografts treated with Fn14 CAR-T/IL-15 cells did not. IL-15 engineering augmented the antitumor activity of Fn14 CAR-T cells and resulted in significant antitumor effects similar to those of Fn14× CD3 BiTE. Our results suggest that Fn14 is an appropriate target for GBM. Anti-Fn14 BiTE and Fn14-specific CAR-T/IL-15 cells may be exciting immunotherapeutic options for malignant brain cancer.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Imunoterapia , Camundongos , Linfócitos T , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Biomolecules ; 11(4)2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804835

RESUMO

Antimicrobial peptides (AMPs), which are evolutionarily conserved components of the innate immune response, contribute to the first line of defense against microbes in the skin and at mucosal surfaces. Here, we report the identification of a human peptide, encoded by the chromosome 5 open reading frame 46 (C5orf46) gene, as a type of AMP, which we termed antimicrobial peptide with 64 amino acid residues (AP-64). AP-64 is an anionic amphiphilic peptide lacking cysteines (MW = 7.2, PI = 4.54). AP-64 exhibited significant antibacterial activity against Gram-negative bacteria, including Escherichia coli DH5α, Escherichia coli O157:H7, Vibrio cholerae, and Pseudomonas aeruginosa. Moreover, AP-64 was efficient in combating Escherichia coli O157:H7 infections in a mouse model and exhibited cytotoxic effects against human T-cell lymphoma Jurkat and B-cell lymphoma Raji cells. We also observed that Gm94, encoded by mouse C5orf46 homologous gene, closely resembles AP-64 in its antibacterial properties. Compared with other human AMPs, AP-64 has distinct characteristics, including a longer sequence length, absence of cysteine residues, a highly anionic character, and cell toxicity. Together, this study identified that AP-64 is an AMP worthy of further investigation.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas Sanguíneas/química , Bactérias Gram-Negativas/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/química , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Infecções por Escherichia coli/tratamento farmacológico , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Alinhamento de Sequência
15.
Cancer Immunol Immunother ; 70(9): 2453-2465, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33543339

RESUMO

BACKGROUND: T cell with chimeric antigen receptors (CAR-T) has presented remarkable efficacy for blood cancer as an emerging immunotherapy. However, for solid tumors, the therapeutic efficacy is much impaired due to the lack of infiltration and persistence of CAR-T in tumor tissue. Thus, we constructed an interleukin-7-loaded oncolytic adenovirus and combined the use of oncolytic virus and CAR-T to improve the therapeutic outcome. METHODS: We constructed an interleukin-7-loaded oncolytic adenovirus (oAD-IL7) and a B7H3-targeted CAR-T and explored the efficacy of the single use of oAD-IL7, B7H3-CAR-T, or the combined therapy for glioblastoma in vitro and in vivo. The improved CAR-T anti-tumor efficacy was evaluated according to the proliferation, survival, persistence, exhaustion of T cells, and tumor regression. RESULTS: Constructed oAD-IL7 and B7H3-CAR-T presented moderate cytotoxicity during in vitro study, but failed to induce a thorough and persistent anti-tumor therapeutic efficacy in vivo. The combination of oAD-IL7 and B7H3-CAR-T in vitro resulted in enhanced T cell proliferation and reduced T cell apoptosis. The joint efficacy was further confirmed using tumor-bearing xenograft mice. During in vivo study, the mice treated with both oAD-IL7 and B7H3-CAR-T showed prolonged survival and reduced tumor burden. According to the ex vivo study, oAD-IL7 improved the proliferation and persistence of tumor-infiltrating B7H3-CAR-T, but failed to reverse the exhaustion. CONCLUSIONS: Our results indicated that oAD-IL7 is a promising auxiliary therapy to improve the therapeutic efficacy of B7H3-CAR-T in glioblastoma by providing the activating signals for tumor-infiltrating T cells. Our results also lay the basis for the future clinical trials for the combination of IL7-loaded oncolytic adenovirus and CAR-T therapy for glioblastoma.


Assuntos
Terapia Genética , Vetores Genéticos/genética , Imunoterapia Adotiva , Interleucina-7/genética , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Adenoviridae/genética , Animais , Apoptose/genética , Apoptose/imunologia , Antígenos B7/antagonistas & inibidores , Antígenos B7/imunologia , Antígenos B7/metabolismo , Citocinas/metabolismo , Citotoxicidade Imunológica , Modelos Animais de Doenças , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Glioblastoma/etiologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Imunofenotipagem , Imunoterapia Adotiva/métodos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Terapia Viral Oncolítica/métodos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Chem Commun (Camb) ; 57(10): 1234-1237, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33416808

RESUMO

The hydrogen evolution reaction is a huge challenge for CO2 electroreduction. Herein, an inside-mode indium oxide/carbon nanotube compound (MWCNTs@In2O3) is developed to maximize the catalytic effect and suppress hydrogen evolution, its HCOOH selectivity can reach up to 92.2% at -16.8 mA cm-2, which is more efficient than In2O3.

17.
Chem Sci ; 12(48): 16065-16073, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-35024128

RESUMO

Development of a covalent-organic framework (COF)-based Z-scheme heterostructure is a promising strategy for solar energy driven water splitting, but the construction of a COF-based Z-scheme heterostructure with well-defined architecture, large contact area and intimate contact interfaces is scarce. Herein, we fabricated a direct Z-scheme heterostructure COF-metal sulfide hybrid (T-COF@CdS) with shell-core architecture by self-polymerization of 1,3,5-benzenetricarboxaldehyde and 2,4,6-tris(4-aminophenyl)-1,3,5-triazine in situ on CdS. The formed C-S chemical bonding between T-COF and CdS could provide a very tight and stable interface. Owing to the properly staggered band alignment, strong interfacial interaction and large interfacial contact area between T-COF and CdS, a Z-scheme route for charge separation and transfer is realized, resulting in electron accumulation in CdS for H2O reduction. The obtained Z-scheme heterostructure T-COF@CdS-3 exhibits a high apparent quantum efficiency of 37.8% under 365 nm monochromatic light irradiation, and long-term stability arising from shell-core structures in which the T-COF shell protects the catalytic centers of CdS against deactivation, as well as acts as oxidation sites to avoid the photocorrosion of CdS. This work provides a strategy for the construction of a shell-core direct Z-scheme heterostructure photocatalyst for water splitting with high performance.

18.
Environ Technol ; 42(9): 1402-1410, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31550211

RESUMO

The polar modified dendritic post-cross-linked polymer, namely HCPD was synthesized and used for adsorptive removal of Cu2+ from aqueous solution. The results showed that 5.12 mmol/g of amino and 2.25 mmol/g of carbonyl groups were uploaded on the polymer and these groups were significantly beneficial for Cu2+ removal. The maximum capacity reached 157.8 mg/g at 313 K and increased as the temperature increased. The Langmuir model characterized the equilibrium data well and a chemical interaction was involved with the enthalpy change of 49.50 kJ/mol. The pseudo-second-order kinetic model described the kinetic data well and the intra-particle diffusion model was appropriate for characterizing the kinetic adsorption. HCPD could be easily regenerated and the regenerated polymers were effectively recycled for five times without significant loss of the equilibrium capacity. Moreover, Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) results revealed that the chelating coordination of the amino and carbonyl groups with Cu2+ was the main driving force for the adsorption.


Assuntos
Polímeros , Poluentes Químicos da Água , Adsorção , Cobre , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Poluentes Químicos da Água/análise
19.
J Colloid Interface Sci ; 587: 121-130, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33360884

RESUMO

Due to the p-π conjugative effect between the nitrogen atom of the amide and the carbonyl, the amide carbonyl has much low reactivity and the Schiff base reaction between the amide and amine usually did not take place, but after the amide was polymerized, it's quite different. Herein, benzene-1,3,5-triyltris((9H-carbazol-9-yl) methanone) (HTCZ) is not able to have the Schiff base reaction with melamine. Surprisingly, after HTCZ was polymerized according to the Friedel-Crafts reaction, the resultant polymer PHTCZ-1 performed the Schiff base reaction with melamine successfully, and a kind of novel N-rich porous organic polymers, namely, PHTCZ-1-MA was successfully synthesized. Moreover, PHTCZ-1-MA owned much higher Brunauer-Emmett-Teller surface area (613 m2·g-1) and pore volume (0.57 cm3·g-1) with very high nitrogen content (42.39 wt%). The theoretical calculation showed that the positive charge of the carbonyl carbon increased by 18% after the polymerization, which greatly improved the reactivity of the carbonyl. Because of this amazing change, PHTCZ-1-MA was proven to be an excellent adsorbent for CO2 capture (180 mg·g-1 at 273 K and 1.0 bar) and mercury(II) adsorption (335 mg·g-1 at 273 K). This study makes the impossibility possible and provides a unique synthesis strategy for the fabrication of a kind of N-rich porous organic polymers.

20.
Front Neurol ; 11: 659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32625165

RESUMO

SARS-CoV-2 is a novel coronavirus leading to serious respiratory disease and is spreading around the world at a raging speed. Recently there is emerging speculations that the central nervous system (CNS) may be involved during SARS-CoV-2 infection, contributing to the respiratory failure. However, the existence of viral replication in CNS has not been confirmed due to the lack of evidence from autopsy specimens. Considering the tropism of SARS-CoV-2, ACE2, is prevailing in CNS, and the neuro-invasive property of human coronavirus was widely reported, there is a need to identified the possible complications during COVID-19 for CNS. In this review, we conduct a detailed summary for the potential of SARS-CoV-2 to infect central nervous system from latest biological fundamental of SARS-CoV-2 to the clinical experience of other human coronaviruses. To confirm the neuro-invasive property of SARS-CoV-2 and the subsequent influence on patients will require further exploration by both virologist and neurologist.

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