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1.
Viruses ; 16(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38400013

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising target to inhibit viral infection. In the current study, the interaction between the receptor-binding domain (RBD) of MERS-CoV and heparin was exploited to assess the inhibitory activity of various sulfated glycans such as glycosaminoglycans, marine-sourced glycans (sulfated fucans, fucosylated chondroitin sulfates, fucoidans, and rhamnan sulfate), pentosan polysulfate, and mucopolysaccharide using Surface Plasmon Resonance. We believe this study provides valuable insights for the development of sulfated glycan-based inhibitors as potential antiviral agents.


Assuntos
Heparina , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Heparina/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Sulfatos/química , Glicosaminoglicanos/metabolismo , Heparitina Sulfato/metabolismo , Mamíferos
2.
J Am Chem Soc ; 146(3): 1926-1934, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38193748

RESUMO

Dielectric capacitors are highly desired in modern electronic devices and power systems to store and recycle electric energy. However, achieving simultaneous high energy density and efficiency remains a challenge. Here, guided by theoretical and phase-field simulations, we are able to achieve a superior comprehensive property of ultrahigh efficiency of 90-94% and high energy density of 85-90 J cm-3 remarkably in strontium titanate (SrTiO3), a linear dielectric of a simple chemical composition, by manipulating local symmetry breaking through introducing Ti/O defects. Atomic-scale characterizations confirm that these Ti/O defects lead to local symmetry breaking and local lattice strains, thus leading to the formation of the isolated ultrafine polar nanoclusters with varying sizes from 2 to 8 nm. These nanoclusters account for both considerable dielectric polarization and negligible polarization hysteresis. The present study opens a new realm of designing high-performance dielectric capacitors utilizing a large family of readily available linear dielectrics with very simple chemistry.

3.
Macromol Biosci ; : e2300375, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37838941

RESUMO

Drug-free macromolecular therapeutics (DFMT) utilizes modified monoclonal antibodies (or antibody fragments) to generate antigen-crosslinking-induced apoptosis in target cells. DFMT is a two-component system containing a morpholino oligonucleotide (MORF1) modified antibody (Ab-MORF1) and human serum albumin conjugated with multiple copies of complementary morpholino oligonucleotide (MORF2), (HSA-(MORF2)x ). The two components recognize each other via the Watson-Crick base pairing complementation of their respective MORFs. One HSA-(MORF2)x molecule can hybridize with multiple Ab-MORF1 molecules on the cell surface, thus serving as the therapeutic crosslink-inducing mechanism of action. Herein, various anti-neoplastic agents in combination with the anti-CD20 Obinutuzumab (OBN)-based DFMT system are examined. Three different classes of chemotherapies are examined: DNA alkylating agents; proliferation pathway inhibitors; and DNA replication inhibitors. Chou-Talalay combination index mathematics is utilized to determine which drugs engaged synergistically with OBN-based DFMT. It is determined that OBN-based DFMT synergizes with topoisomerase inhibitors and DNA nucleotide analogs but is antagonistic with proliferation pathway inhibitors. Cell mechanism experiments are performed to analyze points of synergism or antagonism by investigating Ca2+ influx, mitochondrial health, lysosomal stability, and cell cycle arrest. Finally, the synergistic drug combinatorial effects of OBN-based DFMT with etoposide in vivo are demonstrated using a human xenograft non-Hodgkin's lymphoma mouse model.

4.
J Control Release ; 358: 232-258, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37121515

RESUMO

The concept of multi-targeted immunotherapeutic systems has propelled the field of cancer immunotherapy into an exciting new era. Multi-effector molecules can be designed to engage with, and alter, the patient's immune system in a plethora of ways. The outcomes can vary from effector cell recruitment and activation upon recognition of a cancer cell, to a multipronged immune checkpoint blockade strategy disallowing evasion of the cancer cells by immune cells, or to direct cancer cell death upon engaging multiple cell surface receptors simultaneously. Here, we review the field of multi-specific immunotherapeutics implemented to treat B cell malignancies. The mechanistically diverse strategies are outlined and discussed; common B cell receptor antigen targeting strategies are outlined and summarized; and the challenges of the field are presented along with optimistic insights for the future.


Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Imunoterapia , Linfócitos B
5.
ACS Sens ; 8(3): 956-973, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36892106

RESUMO

Cardiovascular disease (CVD) causes significant mortality and remains the leading cause of death globally. Thus, to reduce mortality, early diagnosis by measurement of cardiac biomarkers and heartbeat signals presents fundamental importance. Traditional CVD examination requires bulky hospital instruments to conduct electrocardiography recording and immunoassay analysis, which are both time-consuming and inconvenient. Recently, development of biosensing technologies for rapid CVD marker screening attracted great attention. Thanks to the advancement in nanotechnology and bioelectronics, novel biosensor platforms are developed to achieve rapid detection, accurate quantification, and continuous monitoring throughout disease progression. A variety of sensing methodologies using chemical, electrochemical, optical, and electromechanical means are explored. This review first discusses the prevalence and common categories of CVD. Then, heartbeat signals and cardiac blood-based biomarkers that are widely employed in clinic, as well as their utilizations for disease prognosis, are summarized. Emerging CVD wearable and implantable biosensors and monitoring bioelectronics, allowing these cardiac markers to be continuously measured are introduced. Finally, comparisons of the pros and cons of these biosensing devices along with perspectives on future CVD biosensor research are presented.


Assuntos
Técnicas Biossensoriais , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Técnicas Biossensoriais/métodos , Prognóstico , Nanotecnologia , Biomarcadores/análise
6.
Curr Biol ; 33(4): 720-726.e2, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36796358

RESUMO

Plants can move in various complex ways in response to external stimuli.1,2 These mechanisms include responses to environmental triggers, such as tropic responses to light or gravity and nastic responses to humidity or contact.3 Nyctinasty, the movements involving circadian rhythmic folding at night and opening at daytime of plant leaves or leaflets, has attracted the attention of scientists and the public for centuries.4,5 In his canonical work entitled The Power of Movement in Plants, Charles Darwin carried out pioneering observations to document the diverse range of movements in plants.6 His systematic examination of plants showing "sleep [folding] movements of leaves" led him to conclude that the legume family (Fabaceae) includes many more nyctinastic species than all other families combined.3 Darwin also found that a specialized motor organ, the pulvinus, is responsible for most sleep movements of plant leaves, although differential cell division and the hydrolysis of glycosides and phyllanthurinolactone also facilitate nyctinasty in some plants.7,8 However, the origin, evolutionary history, and functional benefits of foliar sleep movements remain ambiguous owing to the lack of fossil evidence for this process. Here, we document the first fossil evidence of foliar nyctinasty based on a symmetrical style of insect feeding damage (Folifenestra symmetrica isp. nov.) in gigantopterid seed-plant leaves from the upper Permian (∼259-252 Ma) of China. The pattern of insect damage indicates that the host leaves were attacked when mature but folded. Our finding reveals that foliar nyctinasty extends back to the late Paleozoic and evolved independently among various plant lineages.


Assuntos
Fabaceae , Fósseis , Humanos , Herbivoria , Folhas de Planta/fisiologia , Plantas , Ritmo Circadiano/fisiologia , Fabaceae/fisiologia
7.
ACS Appl Mater Interfaces ; 15(1): 2313-2318, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36534513

RESUMO

Domain walls (DWs) in ferroelectric materials are interfaces that separate domains with different polarizations. Charged domain walls (CDWs) and neutral domain walls are commonly classified depending on the charge state at the DWs. CDWs are particularly attractive as they are configurable elements, which can enhance field susceptibility and enable functionalities such as conductance control. However, it is difficult to achieve CDWs in practice. Here, we demonstrate that applying mechanical stress is a robust and reproducible approach to generate CDWs. By mechanical compression, CDWs with a head/tail-to-body configuration were introduced in ultrathin BaTiO3, which was revealed by in-situ transmission electron microscopy. Finite element analysis shows strong strain fluctuation in ultrathin BaTiO3 under compressive mechanical stress. Molecular dynamics simulations suggest that the strain fluctuation is a critical factor in forming CDWs. This study provides insight into ferroelectric DWs and opens a pathway to creating CDWs in ferroelectric materials.

8.
J Fungi (Basel) ; 10(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38248935

RESUMO

Hydrophobins (HFBs) are a group of small, secreted amphipathic proteins of fungi with multiple physiological functions and potential commercial applications. In this study, HFB genes of the edible mushroom, Grifola frondosa, were systematically identified and characterized, and their transcriptional profiles during fungal development were determined. In total, 19 typical class I HFB genes were discovered and bioinformatically analyzed. Gene expression profile examination showed that Gf.hyd9954 was particularly highly upregulated during primordia formation, suggesting its major role as the predominant HFB in the lifecycle of G. frondosa. The wettability alteration profile and the surface modification ability of recombinant rGf.hyd9954 were greater than for the Grifola HFB HGFII-his. rGf.hyd9954 was also demonstrated to form the typical class I HFB characteristic-rodlet bundles. In addition, rGf.hyd9954 was shown to possess nanoparticle characteristics and emulsification activities. This research sheds light on the regulation of fungal development and its association with the expression of HFB genes.

9.
J Agric Food Chem ; 70(49): 15464-15473, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36454954

RESUMO

Curcumin, a polyphenol derived from turmeric, has multiple biological functions, such as anti-inflammatory, antioxidant, antibacterial and, above all, antitumor activity. Colorectal cancer is a common malignancy of the gastrointestinal tract with an extremely high mortality rate. However, the low bioavailability and poor targeting properties of curcumin generally limit its clinical application. In the present study, we designed a fusion protein GE11-HGFI as a nanodrug delivery system. The protein was connected by flexible linkers, inheriting the self-assembly properties of hydrophobin HGFI and the targeting ability of GE11. The data show that the encapsulation of curcumin by fusion protein GE11-HGFI can form uniform and stable nanoparticles with a size of only 80 nm. In addition, the nanocarrier had high encapsulation efficiency for curcumin and made it to release sustainably. Notably, the drug-loaded nanosystem selectively targeted colorectal cancer cells with high epidermal growth factor receptor expression, resulting in high aggregated concentrations of curcumin at tumor sites, thus showing a significant anticancer effect. These results suggest that the nanocarrier fusion protein has the potential to be a novel strategy for enhancing molecular bioactivity and drug targeting in cancer therapy.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Curcumina , Nanopartículas , Humanos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Receptores ErbB/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética
10.
Biomed Res Int ; 2022: 6087751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212709

RESUMO

Tumor immunotherapy is considered as one of the most promising methods in cancer treatment in recent years. Immune checkpoint blockade (ICB) can activate immune cells to destroy tumors by relieving the inhibitory pathway of tumor cells to immune cells. In silico prediction of the ICB response is an important step toward achieving effective and personalized cancer immunotherapy. Although immune checkpoint inhibitors have shown exciting clinical effects in the treatment of many types of tumors, there are still some clinical problems in practical application, such as low response rate and large individualized differences. How to predict the efficacy of effective individualized immune checkpoint inhibitors for tumor patients based on specific biomarkers and computational models is one of the key issues in the immunotherapy of this kind of tumor. In our work, from the five levels of genome level, transcription level, epigenetic level, microbial taxonomy level, and the immune cell infiltration profile level, the biomarkers and in silico calculation methods that affect the efficacy of tumor immune checkpoint inhibitors are comprehensively summarized.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Biomarcadores , Biomarcadores Tumorais , Biologia Computacional , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente Tumoral
11.
Genes (Basel) ; 13(9)2022 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-36140800

RESUMO

Nitrogen (N) is one of the most important factors affecting crop production. Root morphology exhibits a high degree of plasticity to nitrogen deficiency. However, the mechanisms underlying the root foraging response under low-N conditions remain poorly understood. In this study, we analyzed 213 maize inbred lines using hydroponic systems and regarding their natural variations in 22 root traits and 6 shoot traits under normal (2 mM nitrate) and low-N (0 mM nitrate) conditions. Substantial phenotypic variations were detected for all traits. N deficiency increased the root length and decreased the root diameter and shoot related traits. A total of 297 significant marker-trait associations were identified by a genome-wide association study involving different N levels and the N response value. A total of 51 candidate genes with amino acid variations in coding regions or differentially expressed under low nitrogen conditions were identified. Furthermore, a candidate gene ZmNAC36 was resequenced in all tested lines. A total of 38 single nucleotide polymorphisms and 12 insertions and deletions were significantly associated with lateral root length of primary root, primary root length between 0 and 0.5 mm in diameter, primary root surface area, and total length of primary root under a low-N condition. These findings help us to improve our understanding of the genetic mechanism of root plasticity to N deficiency, and the identified loci and candidate genes will be useful for the genetic improvement of maize tolerance cultivars to N deficiency.


Assuntos
Estudo de Associação Genômica Ampla , Zea mays , Aminoácidos/genética , Perfilação da Expressão Gênica , Nitratos/metabolismo , Nitrogênio/metabolismo , Raízes de Plantas/metabolismo , Plântula/genética
12.
J Control Release ; 350: 584-599, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36037975

RESUMO

Drug-Free Macromolecular Therapeutics (DFMT) is a new paradigm in macromolecular therapeutics that induces apoptosis in target cells by crosslinking receptors without the need of low molecular weight drugs. Programmed cell death is initiated via a biomimetic receptor crosslinking strategy using a two-step approach: i) recognition of cell surface antigen by a morpholino oligonucleotide-modified antibody Fab' fragment (Fab'-MORF1), ii) followed by crosslinking with a multivalent effector motif - human serum albumin (HSA) grafted with multiple complementary morpholino oligonucleotides (HSA-(MORF2)x). This approach is effective in vitro, in vivo, and ex vivo on cells from patients diagnosed with various B cell malignancies. We have previously demonstrated DFMT can be applied to crosslink CD20 and CD38 receptors to successfully initiate apoptosis. Herein, we show simultaneous engagement, and subsequent crosslinking of both targets ("heteroreceptor crosslinking"), can further enhance the apoptosis induction capacity of this system. To accomplish this, we incubated Raji (CD20+; CD38+) cells simultaneously with anti-CD20 and anti-CD38 Fab'-MORF1 conjugates, followed by addition of the macromolecular crosslinker, HSA-(MORF2)x to co-cluster the bound receptors. Fab' fragments from Rituximab and Obinutuzumab were employed in the synthesis of anti-CD20 bispecific engagers (Fab'RTX-MORF1 and Fab'OBN-MORF1), whereas Fab' fragments from Daratumumab and Isatuximab (Fab'DARA-MORF1 and Fab'ISA-MORF1) targeted CD38. All heteroreceptor crosslinking DFMT combinations demonstrated potent apoptosis induction and exhibited synergistic effects as determined by Chou-Talalay combination index studies (CI < 1). In vitro fluorescence resonance energy transfer (FRET) experiments confirmed the co-clustering of the two receptors on the cell surface in response to the combination treatment. The source of this synergistic therapeutic effect was further explored by evaluating the effect of combination DFMT on key apoptosis signaling events such as mitochondrial depolarization, caspase activation, lysosomal enlargement, and homotypic cell adhesion. Finally, a xenograft mouse model of CD20+/CD38+ Non Hodgkin lymphoma was employed to demonstrate in vivo the enhanced efficacy of the heteroreceptor-crosslinking DFMT design versus single-target systems.


Assuntos
Antígenos CD20 , Apoptose , Animais , Caspases/farmacologia , Humanos , Fragmentos Fab das Imunoglobulinas , Substâncias Macromoleculares , Camundongos , Morfolinos , Rituximab/farmacologia , Albumina Sérica Humana
13.
Cancer Manag Res ; 14: 2469-2483, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991677

RESUMO

Radiation pneumonitis is a common and serious complication of radiotherapy for thoracic tumours. Although radiotherapy technology is constantly improving, the incidence of radiation pneumonitis is still not low, and severe cases can be life-threatening. Once radiation pneumonitis develops into radiation fibrosis (RF), it will have irreversible consequences, so it is particularly important to prevent the occurrence and development of radiation pneumonitis. Immune checkpoint inhibitors (ICIs) have rapidly altered the treatment landscape for multiple tumour types, providing unprecedented survival in some patients, especially for the treatment of non-small cell lung cancer (NSCLC). However, in addition to its remarkable curative effect, ICls may cause immune-related adverse events. The incidence of checkpoint inhibitor pneumonitis (CIP) is 3% to 5%, and its mortality rate is 10% to 17%. In addition, the incidence of CIP in NSCLC is higher than in other tumour types, reaching 7%-13%. With the increasing use of immune checkpoint inhibitors (ICls) and thoracic radiotherapy in the treatment of patients with NSCLC, ICIs may induce delayed radiation pneumonitis in patients previously treated with radiation therapy, or radiation activation of the systemic immune system increases the toxicity of adverse reactions, which may lead to increased pulmonary toxicity and the incidence of pneumonitis. In this paper, the data about the occurrence of radiation pneumonitis, immune pneumonitis, and combined treatment and the latest related research results will be reviewed.

14.
Acta Biochim Biophys Sin (Shanghai) ; 54(6): 864-873, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35713313

RESUMO

High-throughput sequencing for B cell receptor (BCR) repertoire provides useful insights for the adaptive immune system. With the continuous development of the BCR-seq technology, many efforts have been made to develop methods for analyzing the ever-increasing BCR repertoire data. In this review, we comprehensively outline different BCR repertoire library preparation protocols and summarize three major steps of BCR-seq data analysis, i. e., V(D)J sequence annotation, clonal phylogenetic inference, and BCR repertoire profiling and mining. Different from other reviews in this field, we emphasize background intuition and the statistical principle of each method to help biologists better understand it. Finally, we discuss data mining problems for BCR-seq data and with a highlight on recently emerging multiple-sample analysis.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Receptores de Antígenos de Linfócitos B , Células Cultivadas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Filogenia , Receptores de Antígenos de Linfócitos B/genética
15.
Sensors (Basel) ; 22(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35590899

RESUMO

The research of object classification and part segmentation is a hot topic in computer vision, robotics, and virtual reality. With the emergence of depth cameras, point clouds have become easier to collect and increasingly important because of their simple and unified structures. Recently, a considerable number of studies have been carried out about deep learning on 3D point clouds. However, data captured directly by sensors from the real-world often encounters severe incomplete sampling problems. The classical network is able to learn deep point set features efficiently, but it is not robust enough when the method suffers from the lack of point clouds. In this work, a novel and general network was proposed, whose effect does not depend on a large amount of point cloud input data. The mutual learning of neighboring points and the fusion between high and low feature layers can better promote the integration of local features so that the network can be more robust. The specific experiments were conducted on the ScanNet and Modelnet40 datasets with 84.5% and 92.8% accuracy, respectively, which proved that our model is comparable or even better than most existing methods for classification and segmentation tasks, and has good local feature integration ability. Particularly, it can still maintain 87.4% accuracy when the number of input points is further reduced to 128. The model proposed has bridged the gap between classical networks and point cloud processing.


Assuntos
Robótica , Realidade Virtual , Computação em Nuvem , Redes Neurais de Computação
16.
Medicine (Baltimore) ; 101(7): e28848, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35363182

RESUMO

BACKGROUND: Coronary heart disease (CHD) has a high incidence rate as a cardiovascular condition, primarily affecting the elderly and middle-aged individuals. CHD has debilitating effects on the standard of life of the elderly, and affecting their physical and psychological health. Reportedly, using aspirin alone is less effective as a first line of treatment for CHD. Therefore, this systematic review and meta-analysis will synthesize evidence on the effectiveness and safeness of aspirin combination treatment in treating patients with CHD. METHODS: A comprehensive meta-analysis is to be performed to evaluate the effectiveness and safety of aspirin combination treatment for CHD patients. A search will be performed on PubMed, EMBASE, Cochrane Central, WanFang, and Chinese National Knowledge Infrastructure till December 25, 2021 to identify randomized controlled trials, assess all related studies on the aspirin combination treatment in treating patients with CHD. In this systematic review, we will adopt the second version of Cochrane risk of bias assessment tool to assess the bias risk in all studies that fulfil the eligibility conditions. Two authors will separately conduct the study selection process, risk of bias assessment, and data extraction. Moreover, a random-effects meta-analysis will be conducted to synthesize evidence for all outcomes. Provided there is sufficient homogeneity among the studies, we will perform meta-analysis. I2 test will be employed to assess the heterogeneity of the outcomes. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/MDTCA.


Assuntos
Doença das Coronárias , Medicamentos de Ervas Chinesas , Idoso , Aspirina/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Metanálise como Assunto , Pessoa de Meia-Idade , Revisões Sistemáticas como Assunto
17.
World J Surg Oncol ; 20(1): 88, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303867

RESUMO

OBJECTIVE: To explore the mechanism of E2F transcription Factor 1 (E2F-1)-mediated ataxia-telangiectasia-mutated protein (ATM) in cisplatin (DDP)-resistant nasopharyngeal carcinoma (NPC). METHODS: E2F-1 and ATM expression was assessed in DDP-resistant NPC cell lines (CNE2/DDP and HNE1/DDP) and parental cells. Then, DDP-resistant NPC cells were transfected with control shRNA (short hairpin RNA) or E2F-1 shRNAs with or without ATM lentiviral activation particles. The half maximal inhibitory concentration (IC50) was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, and the cell cycle and cell proliferation were measured by flow cytometry and EdU staining, respectively. In addition, the expression of genes and proteins was quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. RESULTS: Both E2F-1 and ATM expression in DDP-resistant NPC cells was much higher than that in parental cells. E2F-1 shRNA reduced ATM expression in DDP-resistant NPC cells, but ATM overexpression had no significant effect on E2F-1. ATM overexpression enhanced DDP resistance in DDP-resistant NPC cells with increased IC50 values, which was reversed by E2F-1 inhibition. Meanwhile, ATM overexpression resulted in upregulation of ABCA2 and ABCA5 in DDP-resistant NPC cells, induced elevations in the transition of the cells into S-phase, and increased cell proliferation with enhanced expression of cyclin E1, CDK2, and Ki67, which was reversed by E2F-1 shRNAs. CONCLUSION: Downregulation of E2F-1, possibly by regulating ATM, could block the cell cycle in the G1 phase and reduce the proliferation of CNE2/DDP cells, thereby reversing the resistance of human NPC cells to DDP.


Assuntos
Ataxia Telangiectasia , Fator de Transcrição E2F1/metabolismo , Neoplasias Nasofaríngeas , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Fatores de Transcrição E2F/metabolismo , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo
18.
Dev Cell ; 57(5): 569-582.e6, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35148836

RESUMO

Differentiation of specialized cell types requires precise cell-cycle control. Plant stomata are generated through asymmetric divisions of a stem-cell-like precursor followed by a single symmetric division that creates paired guard cells surrounding a pore. The stomatal-lineage-specific transcription factor MUTE terminates the asymmetric divisions and commits to differentiation. However, the role of cell-cycle machineries in this transition remains unknown. We discover that the symmetric division is slower than the asymmetric division in Arabidopsis. We identify a plant-specific cyclin-dependent kinase inhibitor, SIAMESE-RELATED4 (SMR4), as a MUTE-induced molecular brake that decelerates the cell cycle. SMR4 physically and functionally associates with CYCD3;1 and extends the G1 phase of asymmetric divisions. By contrast, SMR4 fails to interact with CYCD5;1, a MUTE-induced G1 cyclin, and permits the symmetric division. Our work unravels a molecular framework of the proliferation-to-differentiation switch within the stomatal lineage and suggests that a timely proliferative cell cycle is critical for stomatal-lineage identity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ciclo Celular , Diferenciação Celular , Linhagem da Célula , Desaceleração , Regulação da Expressão Gênica de Plantas , Estômatos de Plantas
19.
Acta Biomater ; 137: 1-19, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34687954

RESUMO

B cells play multiple roles in immune responses related to autoimmune diseases as well as different types of cancers. As such, strategies focused on B cell targeting attracted wide interest and developed intensively. There are several common mechanisms various B cell targeting therapies have relied on, including direct B cell depletion, modulation of B cell antigen receptor (BCR) signaling, targeting B cell survival factors, targeting the B cell and T cell costimulation, and immune checkpoint blockade. Nanocarriers, used as drug delivery vehicles, possess numerous advantages to low molecular weight drugs, reducing drug toxicity, enhancing blood circulation time, as well as augmenting targeting efficacy and improving therapeutic effect. Herein, we review the commonly used targets involved in B cell targeting approaches and the utilization of various nanocarriers as B cell-targeted delivery vehicles. STATEMENT OF SIGNIFICANCE: As B cells are engaged significantly in the development of many kinds of diseases, utilization of nanomedicines in B cell depletion therapies have been rapidly developed. Although numerous studies focused on B cell targeting have already been done, there are still various potential receptors awaiting further investigation. This review summarizes the most relevant studies that utilized nanotechnologies associated with different B cell depletion approaches, providing a useful tool for selection of receptors, agents and/or nanocarriers matching specific diseases. Along with uncovering new targets in the function map of B cells, there will be a growing number of candidates that can benefit from nanoscale drug delivery.


Assuntos
Nanomedicina , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia , Nanotecnologia , Neoplasias/tratamento farmacológico
20.
Artigo em Inglês | MEDLINE | ID: mdl-34675989

RESUMO

Essential hypertension (EH) is a clinically frequent cardiovascular disease, with insidious onset, causing increased pressure load and neuroregulation disorders in patients. Long-term EH can cause left ventricular hypertrophy (LVH), which can lead to arrhythmia and even death. The soluble suppression of tumorigenicity 2 (sST2), matrix metalloproteinase-3 (MMP-3), and galectin-3 (Gal-3) in serum plays an important role in the occurrence, development, and prognosis of cardiovascular diseases. In our study, we divided EH patients into 3 levels and groups with or without LVH, according to their condition. The levels of sST2, MMP-3, and Gal-3 in the serum were measured in different groups of patients. Our results showed that the levels of sST2, MMP-3, and Gal-3 in the serum increased progressively with the level in different EH groups. The levels of sST2, MMP-3, and Gal-3 in the serum of the LVH group were higher than those of the NLVH group, and it is positively correlated with LVH-related indexes. The risk of developing and progressing to LVH in patients with EH can be determined by the method of measuring three indicators.

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