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1.
Front Immunol ; 15: 1359532, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605944

RESUMO

Immunotherapy has revolutionized cancer treatment, with the anti-PD-1/PD-L1 axis therapy demonstrating significant clinical efficacy across various tumor types. However, it should be noted that this therapy is not universally effective for all PD-L1-positive patients, highlighting the need to expedite research on the second ligand of PD-1, known as Programmed Cell Death Receptor Ligand 2 (PD-L2). As an immune checkpoint molecule, PD-L2 was reported to be associated with patient's prognosis and plays a pivotal role in cancer cell immune escape. An in-depth understanding of the regulatory process of PD-L2 expression may stratify patients to benefit from anti-PD-1 immunotherapy. Our review focuses on exploring PD-L2 expression in different tumors, its correlation with prognosis, regulatory factors, and the interplay between PD-L2 and tumor treatment, which may provide a notable avenue in developing immune combination therapy and improving the clinical efficacy of anti-PD-1 therapies.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Ligantes , Neoplasias/terapia , Prognóstico , Apoptose
2.
Heliyon ; 10(3): e25023, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38317931

RESUMO

Non-invasive external energy triggered efficient tumor therapy is a promising specific treatment strategy. Herein, a composite material of bismuth sodium titanate (BNT) and molybdenum disulfide (MoS2) with piezoelectric effect was designed for the synergistic treatment of breast cancer with near-infrared-II (NIR-II) light and ultrasound (US) activation. The BNT@MoS2 exhibit excellent photothermal and acoustic properties upon excitation by 1060 nm NIR-II laser and US, respectively. The synergistic effect of hyperthermia and reactive oxygen species (ROS) under photoacoustic action endows the BNT@MoS2 with remarkable anti-tumor activities, enabling them to eradicate breast cancer cells within 10 min. The work could provide new insights into the treatment of breast cancer.

3.
BMC Genomics ; 25(1): 132, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302871

RESUMO

BACKGROUND: The U-box gene family encodes E3 ubiquitin ligases involved in plant hormone signaling pathways and abiotic stress responses. However, there has yet to be a comprehensive analysis of the U-box gene family in maize (Zea mays L.) and its responses to abiotic stress. RESULTS: In this study, 85 U-box family proteins were identified in maize and were classified into four subfamilies based on phylogenetic analysis. In addition to the conserved U-box domain, we identified additional functional domains, including Pkinase, ARM, KAP and Tyr domains, by analyzing the conserved motifs and gene structures. Chromosomal localization and collinearity analysis revealed that gene duplications may have contributed to the expansion and evolution of the U-box gene family. GO annotation and KEGG pathway enrichment analysis identified a total of 105 GO terms and 21 KEGG pathways that were notably enriched, including ubiquitin-protein transferase activity, ubiquitin conjugating enzyme activity and ubiquitin-mediated proteolysis pathway. Tissue expression analysis showed that some ZmPUB genes were specifically expressed in certain tissues and that this could be due to their functions. In addition, RNA-seq data for maize seedlings under salt stress revealed 16 stress-inducible plant U-box genes, of which 10 genes were upregulated and 6 genes were downregulated. The qRT-PCR results for genes responding to abiotic stress were consistent with the transcriptome analysis. Among them, ZmPUB13, ZmPUB18, ZmPUB19 and ZmPUB68 were upregulated under all three abiotic stress conditions. Subcellular localization analysis showed that ZmPUB19 and ZmPUB59 were located in the nucleus. CONCLUSIONS: Overall, our study provides a comprehensive analysis of the U-box gene family in maize and its responses to abiotic stress, suggesting that U-box genes play an important role in the stress response and providing insights into the regulatory mechanisms underlying the response to abiotic stress in maize.


Assuntos
Ubiquitina-Proteína Ligases , Zea mays , Zea mays/metabolismo , Filogenia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Perfilação da Expressão Gênica , Estresse Fisiológico/genética , Ubiquitinas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Família Multigênica
4.
J Biomater Sci Polym Ed ; : 1-33, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340315

RESUMO

Radiological heart damage (RIHD) is damage caused by unavoidable irradiation of the heart during chest radiotherapy, with a long latency period and a progressively increasing proportion of delayed cardiac damage due to conventional doses of chest radiotherapy. There is a risk of inducing diseases such as acute/chronic pericarditis, myocarditis, delayed myocardial fibrosis and damage to the cardiac conduction system in humans, which can lead to myocardial infarction or even death in severe cases. This paper details the pathogenesis of RIHD and gives potential targets for treatment at the molecular and cellular level, avoiding the drawbacks of high invasiveness and immune rejection due to drug therapy, medical device implantation and heart transplantation. Injectable hydrogel therapy has emerged as a minimally invasive tissue engineering therapy to provide necessary mechanical support to the infarcted myocardium and to act as a carrier for various bioactive factors and cells to improve the cellular microenvironment in the infarcted area and induce myocardial tissue regeneration. Therefore, this paper combines bioactive factors and cellular therapeutic mechanisms with injectable hydrogels, presents recent advances in the treatment of cardiac injury after RIHD with different injectable gels, and summarizes the therapeutic potential of various types of injectable hydrogels as a potential solution.

5.
Insights Imaging ; 15(1): 63, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411742

RESUMO

Positron emission tomography/magnetic resonance imaging (PET/MRI) is a hybrid imaging technique that quantitatively combines the metabolic and functional data from positron emission tomography (PET) with anatomical and physiological information from MRI. As PET/MRI technology has advanced, its applications in cancer care have expanded. Recent studies have demonstrated that PET/MRI provides unique advantages in the field of radiotherapy and has become invaluable in guiding precision radiotherapy techniques. This review discusses the rationale and clinical evidence supporting the use of PET/MRI for radiation positioning, target delineation, efficacy evaluation, and patient surveillance.Critical relevance statement This article critically assesses the transformative role of PET/MRI in advancing precision radiotherapy, providing essential insights into improved radiation positioning, target delineation, efficacy evaluation, and patient surveillance in clinical radiology practice.Key points• The emergence of PET/MRI will be a key bridge for precise radiotherapy.• PET/MRI has unique advantages in the whole process of radiotherapy.• New tracers and nanoparticle probes will broaden the use of PET/MRI in radiation.• PET/MRI will be utilized more frequently for radiotherapy.

6.
Int J Mol Sci ; 25(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38256188

RESUMO

Nucleotidyl transferases (NTPs) are common transferases in eukaryotes and play a crucial role in nucleotide modifications at the 3' end of RNA. In plants, NTPs can regulate RNA stability by influencing 3' end modifications, which in turn affect plant growth, development, stress responses, and disease resistance. Although the functions of NTP family members have been extensively studied in Arabidopsis, rice, and maize, there is limited knowledge about NTP genes in soybeans. In this study, we identified 16 members of the NTP family in soybeans, including two subfamilies (G1 and G2) with distinct secondary structures, conserved motifs, and domain distributions at the protein level. Evolutionary analysis of genes in the NTP family across multiple species and gene collinearity analysis revealed a relatively conserved evolutionary pattern. Analysis of the tertiary structure of the proteins showed that NTPs have three conserved aspartic acids that bind together to form a possible active site. Tissue-specific expression analysis indicated that some NTP genes exhibit tissue-specific expression, likely due to their specific functions. Stress expression analysis showed significant differences in the expression levels of NTP genes under high salt, drought, and cold stress. Additionally, RNA-seq analysis of soybean plants subjected to salt and drought stress further confirmed the association of soybean NTP genes with abiotic stress responses. Subcellular localization experiments revealed that GmNTP2 and GmNTP14, which likely have similar functions to HESO1 and URT1, are located in the nucleus. These research findings provide a foundation for further investigations into the functions of NTP family genes in soybeans.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Nucleotidiltransferases , Soja/genética , Resposta ao Choque Frio , Nucleotídeos , RNA Nucleotidiltransferases
7.
J Appl Biomater Funct Mater ; 21: 22808000231218996, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38131321

RESUMO

With the rising incidence of cancer, radiotherapy has become an increasingly popular treatment modality. However, radiation-induced skin injuries (RSIs) have emerged as a commonly reported side effect of radiotherapy, thereby presenting a significant challenge in the field of radiotherapy. In this study, we report the successful synthesis of a photosensitive hydrogel via amide reaction for grafting the photosensitive group, methacrylate anhydride (MA), onto chitosan (CHI) and gelatin (GEL), with subsequent physical incorporation of epigallocatechin gallate (EGCG). The resulting composite photosensitive hydrogels exhibited favorable swelling properties, rheological properties, and biocompatibility, which promote angiogenesis and demonstrate notable therapeutic efficacy against RSIs. These findings provide valuable insights into the clinical utility of EGCG composite hydrogels for the effective management of RSIs.


Assuntos
Catequina , Hidrogéis , Catequina/farmacologia , Catequina/uso terapêutico , Gelatina
8.
Mikrochim Acta ; 191(1): 52, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147136

RESUMO

Coconut cadang-cadang viroid (CCCVd) is an infectious single-stranded RNA (ssRNA) pathogen, which leads directly to the death of a large number of coconut palm trees and heavy economic loss to coconut farmers. Herein, a novel electrochemical impedance RNA genosensor is presented based on highly stable gold nanoparticles (AuNPs) decorated phosphorene (BP) nanohybrid with graphene (Gr) for highly sensitive, low-cost, and label-free detection of CCCVd. BP-AuNPs are environmentally friendly prepared by ultrasonic-assisted liquid-phase exfoliation of black phosphorus, accompanying direct reduction of chloroauric acid. Gr/BP-AuNPs are facilely prepared by the in situ growth of AuNPs onto the BP surface and its nanohybrid with Gr to improve environmental stability of BP. Gr/BP-AuNP-based RNA genosensor is fabricated by immobilizing the thiol-functionalized single-stranded DNA (ssDNA) oligonucleotide probe onto the surface of Gr/BP-AuNP-modified glassy carbon electrode via gold-thiol interactions, which served as an electrochemical genosensing platform for the label-free impedance detection of CCCVd by hybridization between the functionalized ssDNA probe and the complementary CCCVd ssRNA sequence in a wide linear range from 1.0 × 10-11 to 1.0 × 10-7 M with a low limit of detection of 2.8 × 10-12 M. This work supplies an experimental support and theoretical direction for the fabrication of RNA biosensors based on graphene-like materials and potential application for a specific diagnosis of plant RNA viral disease in Arecaceae planting industry.


Assuntos
Grafite , Nanopartículas Metálicas , Ouro , DNA de Cadeia Simples , Compostos de Sulfidrila
9.
Biomed Mater ; 19(1)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38000084

RESUMO

The chest wall is the most frequent metastatic site of breast cancer (BC) and the metastasis usually occurs in a solitary setting. Chest wall resection is a way to treat solitary BC metastasis, but intraoperative bone defects and local tumor recurrence still affect the life quality of patients. Titanium-based prostheses are widely used for chest wall repair and reconstruction, but their inherent bio-inertness makes their clinical performance unfavorable. Nanostructured surfaces can give titanium substrates the ability to excellently modulate a variety of cellular functions. Ascorbic acid is a potential stimulator of tumor suppression and osteogenic differentiation. An ascorbic acid-decorated nanostructured titanium surface was prepared through alkali treatment and spin-coating technique and its effects on the biological responses of BC cells and osteoblasts were assessed. The results exhibited that the nanorod structure and ascorbic acid synergistically inhibited the proliferation, spreading, and migration of BC cells. Additionally, the ascorbic acid-decorated nanostructured surface significantly promoted the proliferation and osteogenic differentiation of osteoblasts. This work may provide valuable references for the clinical application of titanium materials in chest wall reconstruction after the resection of metastatic BC.


Assuntos
Neoplasias da Mama , Nanoestruturas , Humanos , Feminino , Titânio/química , Osteogênese , Nanoestruturas/química , Diferenciação Celular , Propriedades de Superfície , Osteoblastos
10.
Ann Med ; 55(2): 2282181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37983527

RESUMO

Purpose: To assess the impact of neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment (TIME) in gynaecological tumors, with a focus on understanding the potential for enhanced combination therapies.Methods: We systematically queried the PubMed, Embase, and Cochrane databases, encompassing reviews, clinical trials, and case studies, to undertake a thorough analysis of the impact of NACT on the TIME of gynaecological tumors.Results: NACT induces diverse immune microenvironment changes in gynaecological tumors. In cervical cancer, NACT boosts immune-promoting cells, enhancing tumor clearance. Ovarian cancer studies yield variable outcomes, influenced by patient-specific factors and treatment regimens. Limited research exists on NACT's impact on endometrial cancer's immune microenvironment, warranting further exploration. In summary, NACT-induced immune microenvironment changes display variability. Clinical trials highlight personalized immunotherapy's positive impact on gynaecological tumor prognosis, suggesting potential avenues for future cancer treatments. However, rigorous investigation is needed to determine the exact efficacy and safety of combining NACT with immunotherapy.Conclusion: This review provides a solid foundation for the development of late-stage immunotherapy and highlights the importance of therapeutic strategies targeting immune cells in TIME in anti-tumor therapy.


The abnormal tumour microenvironment in gynaecological tumours can impede the penetration and accumulation of chemotherapeutic drugs, leading to poorer drug therapy efficacy.Neoadjuvant chemotherapy can improve the surgical resection rate of patients while regulating the ratio of each immune cell subpopulation to achieve the regulation of the tumour microenvironment, thus achieving anti-tumour effects.Based on the immune variability of patients after neoadjuvant chemotherapy, selecting the most suitable individualized immunotherapy will become a promising new therapy.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Ovarianas/patologia , Prognóstico , Quimioterapia Adjuvante , Microambiente Tumoral
11.
J Integr Med ; 21(6): 593-604, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37805293

RESUMO

OBJECTIVE: The aim of this study is to identify molecules from traditional Chinese medicine (TCM) with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. METHODS: We applied the Apriori algorithm to identify important combinations of herbs in the TCM prescriptions for the treatment of coronavirus disease 2019 (COVID-19). Then, we explored the active components and core targets using network pharmacology. In addition, the molecular docking approach was performed to investigate the interaction of these components with the main structural and non-structural proteins, as well as the mutants. Furthermore, their stability in the binding pockets was further evaluated with the molecular dynamics approach. RESULTS: A combination of Amygdalus Communis Vas., Ephedra Herba and Scutellaria baicalensis Georgi was selected as the important herbal combination, and 11 main components and 20 core targets against COVID-19 were obtained. These components, including luteolin, naringenin, stigmasterol, baicalein, and so on, were the potentially active compounds against COVID-19. The binding affinity of these compounds with the potential targets was as high as the positive controls. Among them, baicalein could interfere with multiple targets simultaneously, and it also interfered with the interaction between spike protein and angiotensin-converting enzyme 2 receptor. Additionally, almost all the systems reached stability during dynamics simulation. CONCLUSION: The combination of A. communis, Ephedra Herba and S. baicalensis was the most important herbal combination for the treatment of COVID-19. Baicalein may be a potential candidate against SARS-CoV-2 and its variants. Please cite this article as: Song JB, Zhao LQ, Wen HP, Li YP. Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study. J Integr Med. 2023;21(6):593-604.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2 , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa
12.
J Colloid Interface Sci ; 652(Pt B): 1673-1684, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37666199

RESUMO

After resection of bone tumour, the risk of cancer recurrence and numerous bone defects continues to threaten the health of patients. To overcome the challenge, we developed a novel multifunctional scaffold material consisting mainly of nano-hydroxyapatite particles (n-HA), MXene nanosheets and g-C3N4 to prevent tumour recurrence and promote bone formation. N-HA has the potential to restrict the growth of osteosarcoma cells, and the combination of MXene and g-C3N4 enables the scaffolds to produce photodynamic and photothermal effects simultaneously under near infrared (NIR) irradiation. Surprisingly, n-HA can further enhance the synergistic anti-tumour function of photodynamic and photothermal, and the scaffolds can eradicate osteosarcoma cells in only 10 min at a mild temperature of 45 ℃. Moreover, the scaffold exhibit exceptional cytocompatibility and possesses the capacity to induce osteogenic differentiation of bone marrow mesenchymal stem cells. Therefore, this multifunctional scaffold can not only inhibits the proliferation of bone tumour cells and rapidly eradicate bone tumour through NIR irradiation, but also enhances osteogenic activity. This promising measure can be used to treat tissue damage after bone tumour resection.

13.
J Am Chem Soc ; 145(16): 9273-9284, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37070213

RESUMO

The liquid phase of metal-organic frameworks (MOFs) is key for the preparation of melt-quenched bulk glasses as well as the shaping of these materials for various applications; however, only very few MOFs can be melted and transformed into stable glasses. Here, the solvothermal and mechanochemical preparation of a new series of functionalized derivatives of ZIF-4 (Zn(im)2, where im- = imidazolate and ZIF = zeolitic imidazolate framework) containing the cyano-functionalized imidazolate linkers CNim- (4-cynanoimidazolate) and dCNim- (4,5-dicyanoimidazolate) is reported. The strongly electron-withdrawing nature of the CN groups facilitates low-temperature melting of the materials (below 310 °C for some derivatives) and the formation of microporous ZIF glasses with remarkably low glass-transition temperatures (down to only about 250 °C) and strong resistance against recrystallization. Besides conventional ZIF-4, the CN-functionalized ZIFs are so far the only MOFs to show an exothermic framework collapse to a low-density liquid phase and a subsequent transition to a high-density liquid phase. By systematic adjustment of the fraction of cyano-functionalized linkers in the ZIFs, we derive fundamental insights into the thermodynamics of the unique polyamorphic nature of these glass formers as well as further design rules for the porosity of the ZIF glasses and the viscosity of their corresponding liquids. The results provide new insights into the unusual phenomenon of liquid-liquid transitions as well as a guide for the chemical diversification of meltable MOFs, likely with implications beyond the archetypal ZIF glass formers.

14.
J Int Med Res ; 51(1): 3000605221148895, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650910

RESUMO

OBJECTIVE: To explore the epidemiological characteristics of patients with lymphoepithelial carcinoma (LEC) of the head and neck and the prognostic factors. METHODS: We conducted a retrospective cohort study of cases of head and neck LEC retrieved from the Surveillance, Epidemiology and End Results database. Kaplan-Meier survival analysis and the log-rank test were employed to assess overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate analyses were used to construct Cox regression models. We established nomograms to predict OS and CSS among patients with nasopharyngeal LEC, who were divided into high- and low-risk groups based on the OS nomograms to compare the effects of treatment using the restricted mean survival time (RMST). RESULTS: The 5-year OS and CSS rates of the cohort were 70.8% and 74.8%, respectively. Advanced age, unmarried status, black race, distant metastasis, and the absence of surgical treatment were significantly associated with decreased survival rates. RMST did not differ between the combined treatment (radiotherapy and chemotherapy) and radiotherapy monotherapy groups, but chemotherapy alone displayed poor efficacy. CONCLUSIONS: Head and neck LEC is associated with a favorable prognosis. Radiotherapy plays a significant role in managing patients with nasopharyngeal LEC, which is influenced by multiple prognostic factors.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Prognóstico , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia
15.
Int J Mol Sci ; 23(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36142864

RESUMO

Progesterone is a steroid hormone that performs important functions in mammals. However, studies on its physiological functions in plants have gradually increased in recent years. Therefore, this review summarizes the regulatory functions of progesterone on plant growth and development, as well as its response to stress. Moreover, the plant metabolic processes of progesterone are also discussed. Overall, progesterone is ubiquitous in plants and can regulate numerous plant physiological processes at low concentrations. Since progesterone shares similar characteristics with plant hormones, it is expected to become a candidate for plant hormone. However, most of the current research on progesterone in plants is limited to the physiological level, and more molecular level research is needed to clarify progesterone signaling pathways.


Assuntos
Reguladores de Crescimento de Plantas , Progesterona , Animais , Regulação da Expressão Gênica de Plantas , Mamíferos/metabolismo , Desenvolvimento Vegetal , Reguladores de Crescimento de Plantas/metabolismo , Plantas/metabolismo , Progesterona/metabolismo , Estresse Fisiológico/fisiologia
16.
Hum Cell ; 35(6): 1838-1855, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36087219

RESUMO

Liver is a well-known immunological organ with unique microenvironment. In normal conditions, the rich immune-infiltrating cells cooperate with non-parenchymal cells, such as Kupffer cells (KCs). The presence of liver immunosuppressive microenvironment underlines the importance to dissect this interaction to understand how this cross-talk promotes tumor growth in hepatocellular carcinoma (HCC). Therefore, the aim of the study here was to probe the role of methyltransferase-like 3 (METTL3) in the HCC progression and its effect on the polarization of KCs. KCs showed M2 polarization, and METTL3 was overexpressed in our collected HCC tissues relative to adjacent tissues. METTL3 depletion inhibited the M2 polarization of KCs, thereby reverting the malignant phenotype of HCC cells in vitro and growth and metastasis in vivo. Mechanistically, YTH domain-containing family protein 1 (YTHDF1) bound to RNA-binding protein 14 (RBM14), whereas METTL3 knockdown in KCs cells suppressed RBM14 expression by decreasing N-methyladenosine (m6A) methylation. Overexpression of RBM14 mitigated the anti-tumor effects of sh-METTL3 in vitro and in vivo. It is suggested that the mechanism of sh-METTL3 suppressing the polarization of KCs and the progression of HCC is to regulate the RBM14 expression via YTHDF1-dependent m6A modification.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenosina/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Metilação de DNA , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metiltransferases/genética , Metiltransferases/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Microambiente Tumoral
17.
Mol Immunol ; 151: 204-217, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36179603

RESUMO

Atypical chemokine receptor 3 (ACKR3) has been linked to the tumor microenvironment. This work investigates the effects of ACKR3 and its regulatory molecules on the chemotactic migration of tumor-associated macrophages (TAMs) in hepatocellular carcinoma (HCC). RT-qPCR and western blot assays identified elevated ACKR3 and HDAC2 levels in HCC tissues and cells. Knockdown or overexpression of ACKR3 was induced in HCC cells through vectors of lentivirus plasmids, and then the conditioned medium of the HCC cells was collected to stimulate TAMs. The stimulated TAMs were co-cultured with CD3+ T cells. ACKR3 knockdown in HCC cells inhibited migration of TAMs and promoted M1 polarization, which restored the activity of T cells. Histone deacetylase 2 (HDAC2) recruited signal transducer and activator of transcription 1 (STAT1) to the ACKR3 promoter to activate ACKR3 transcription. HDAC2 silencing suppressed nuclear translocation of STAT1 and decreased ACKR3 expression. HDAC2 knockdown in HCC cells similarly suppressed TAM migration, promoted M1 polarization, and restored T cell function, but these changes were inversed by ACKR3 upregulation. HDAC2 or ACKR3 silencing weakened tumor growth and immune escape in mice. In conclusion, this study demonstrates that HDAC2 upregulates ACKR3 via STAT1 to induce migration of M2 macrophages and immune escape in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Receptores CXCR/metabolismo , Animais , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/metabolismo , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Macrófagos , Camundongos , Fator de Transcrição STAT1/metabolismo , Microambiente Tumoral , Regulação para Cima
18.
Environ Sci Pollut Res Int ; 29(58): 87983-87997, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35821323

RESUMO

Global warming caused by increased carbon emissions is a common challenge for all mankind. Facing the unprecedented pressure of carbon emission reduction, it is particularly important to grasp the dynamics of carbon emission in time and accurately. This paper proposes a novel daily carbon emission forecasting model. Firstly, the daily carbon emission data is decomposed into a series of completely noise-free mode functions by improved complete ensemble empirical mode decomposition method with adaptive noise (ICEEMDAN). Then, a two-stage feature selection method composed of partial autocorrelation function (PACF) and ReliefF is applied to select appropriate input variables for the next prediction process. Finally, the extreme learning machine optimized by improved sparrow search algorithm (ISSA-ELM) is used to predict. The empirical results show that the proposed two-stage feature selection method can further improve the prediction accuracy. After two-stage feature selection, the values of R2, MAPE, and RMSE were improved by 0.55%, 30.23%, and 28.46%, respectively. It can also be found that ISSA has good optimization performance. By combining with ISSA, R2, MAPE, and RMSE improved by 7.60%, 31.97%, and 44.79%, respectively. Therefore, the proposed model can provide a valuable reference for the formulation of carbon emission reduction policies and future carbon emission prediction research.


Assuntos
Algoritmos , Carbono , Previsões
19.
Colloids Surf B Biointerfaces ; 217: 112615, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35759893

RESUMO

The recurrence and bone defect of malignant osteosarcoma postsurgical treatment have gained remarkable attention. Therefore, the development of multifunctional treatment platform is urgently desirable to achieve efficient tumor treatment and bone regeneration. In this paper, a multifunctional nanomaterial using mesoporous silica (MSN) as platform modified with quercetin (Qr), collagen (Col) and dopamine (PDA) was developed. Our findings demonstrated that the nanoparticles designed in this work had excellent photothermal properties and pH responsiveness. In addition, the nanoparticles had outstanding anti-tumor ability and could killed Saos-2 cells within 10 min under 808 nm laser irradiation owing to the synergistic effect of hyperthermia and Qr. Besides, the modification of PDA and Col endows the nanoparticles with excellent osteogenic activity.


Assuntos
Neoplasias Ósseas , Hipertermia Induzida , Nanopartículas , Osteossarcoma , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Doxorrubicina/química , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Fototerapia , Dióxido de Silício/química
20.
Inflammation ; 45(6): 2309-2324, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35715591

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) has been implicated in the progression of liver hepatocellular carcinoma (LIHC). The most important feature of LIHC is the immune escape process. This study sets to study the role of ALDH2 in regulating immune escape in LIHC. Bioinformatics analysis was applied to examine the expression of ALDH2 in LIHC and its impact on patients' survival. The effect of ALDH2 expression on malignant phenotype of LIHC cells was assessed by gain-of-function assays. RT-qPCR and Western blot were conducted to examine the expression of related factors, thus investigating the downstream mechanisms of ALDH2. ELISA assay was carried out to measure the level of oxidative stress in cells, and crystal violet staining was conducted to observe the killing effect of T cells on tumor cells. Finally, xenograft assay was carried out to verify the role of ALDH2 in vivo.ALDH2 was poorly expressed in LIHC, which predicted dismal prognoses for patients. ALDH2 inhibited the malignant aggressiveness of LIHC cells. ALDH2 blocked the activation of Nrf2 by suppressing reactive oxygen species (ROS) in LIHC, and Nrf2 significantly reversed the tumor-suppressing properties of ALDH2. Nrf2 hindered autophagy and led to immune escape of LIHC cells. Moreover, ALDH2 considerably suppressed the growth of xenografts, increased autophagy and promoted the accumulation of T cells in tumors. In contrast, Nrf2 drastically reversed the repressive effect of ALDH2 on tumor growth.ALDH2 impaired the ROS/Nrf2 axis to promote autophagy, thereby repressing immune escape in LIHC.


Assuntos
Aldeído-Desidrogenase Mitocondrial , Autofagia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Evasão Tumoral , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio/metabolismo
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