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1.
EMBO Rep ; 23(2): e53543, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34842321

RESUMO

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for dissecting the complexity of normal and diseased tissues, enabling characterization of cell diversity and heterogeneous phenotypic states in unprecedented detail. However, this technology has been underutilized for exploring the interactions between the host cell and viral pathogens in latently infected cells. Herein, we use scRNA-seq and single-molecule sensitivity fluorescent in situ hybridization (smFISH) technologies to investigate host single-cell transcriptome changes upon the reactivation of a human neurotropic virus, herpes simplex virus-1 (HSV-1). We identify the stress sensor growth arrest and DNA damage-inducible 45 beta (Gadd45b) as a critical antiviral host factor that regulates HSV-1 reactivation events in a subpopulation of latently infected primary neurons. We show that distinct subcellular localization of Gadd45b correlates with the viral late gene expression program, as well as the expression of the viral transcription factor, ICP4. We propose that a hallmark of a "successful" or "aborted" HSV-1 reactivation state in primary neurons is determined by a unique subcellular localization signature of the stress sensor Gadd45b.


Assuntos
Antígenos de Diferenciação/metabolismo , Herpesvirus Humano 1 , Neurônios/virologia , Ativação Viral , Latência Viral , Regulação da Expressão Gênica , Herpesvirus Humano 1/fisiologia , Humanos , Hibridização in Situ Fluorescente , Transcriptoma
2.
BMC Geriatr ; 24(1): 59, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218756

RESUMO

BACKGROUND: The interaction between motor dysfunction and respiratory functions in stroke patients with hemiplegia are not fully understood, particularly with regard to the relationship between changes in trunk control, balance, and daily activities, and changes in respiratory muscle strength and pulmonary volume. Investigating this relationship will facilitate the optimization of stroke rehabilitation strategies. METHODS: Clinical history data were collected from 134 patients to analyze the relationship between motor function scales scores and spirometric data. The data from 60 patients' data were used to evaluate the relationship between motor function scales scores and spirometric data at baseline and after 3-weeks rehabilitation. RESULTS: (1) Patients with lower scores on Trunk impairment Scale (TIS), Berg Balance Scale (BBS) and Barthel Index (BI) had weaker respiratory muscle strength and pulmonary function. (2) Stroke patients' BBS and BI scores showed differences between normal and unnormal maximal inspiratory pressure (MIP), but not in TIS. (3) Improvements in motor function led to promotion of enhanced respiratory function. Patient exhibited less MIP improvement at the severe level of TIS and BBS. CONCLUSIONS: Patients with hemiplegia exhibited diminished respiratory muscle strength and pulmonary function at a more severe motor dysfunction level. Impaired inspiratory muscle strength was associated with reduced balance ability and limitations in activities required for daily living. Enhanced motor function improved respiration and rehabilitation programs should prioritize the activation of diaphragm function to improve overall outcomes.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Hemiplegia/diagnóstico , Hemiplegia/reabilitação , Acidente Vascular Cerebral/complicações , Músculos Respiratórios
3.
Luminescence ; 37(6): 1037-1043, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35332661

RESUMO

As an important reactive oxygen species (ROS), hydrogen peroxide plays a significant role in the life activity system, and its abnormal levels are closely related to many diseases. Developing effective fluorescent probes for detecting hydrogen peroxide is very urgent. Therefore, we constructed a probe Z that can detect hydrogen peroxide in ratio. It has naphthimide as the fluorophore and phenylboronic acid pinacol esters as the recognition group. It shows higher sensitivity, lower detection limit, higher selectivity, and broad pH applicability. Moreover, probe Z has low cytotoxicity that can be used to detect exogenous hydrogen peroxide in HeLa cells and might be a potential tool for studying hydrogen peroxide in physiological activities.


Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Células HeLa , Humanos , Fótons , Espécies Reativas de Oxigênio
4.
BMC Genomics ; 22(1): 612, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384368

RESUMO

BACKGROUND: Soil salinization represents a serious threat to global rice production. Although significant research has been conducted to understand salt stress at the genomic, transcriptomic and proteomic levels, few studies have focused on the translatomic responses to this stress. Recent studies have suggested that transcriptional and translational responses to salt stress can often operate independently. RESULTS: We sequenced RNA and ribosome-protected fragments (RPFs) from the salt-sensitive rice (O. sativa L.) cultivar 'Nipponbare' (NB) and the salt-tolerant cultivar 'Sea Rice 86' (SR86) under normal and salt stress conditions. A large discordance between salt-induced transcriptomic and translatomic alterations was found in both cultivars, with more translationally regulated genes being observed in SR86 in comparison to NB. A biased ribosome occupancy, wherein RPF depth gradually increased from the 5' ends to the 3' ends of coding regions, was revealed in NB and SR86. This pattern was strengthened by salt stress, particularly in SR86. On the contrary, the strength of ribosome stalling was accelerated in salt-stressed NB but decreased in SR86. CONCLUSIONS: This study revealed that translational reprogramming represents an important layer of salt stress responses in rice, and the salt-tolerant cultivar SR86 adopts a more flexible translationally adaptive strategy to cope with salt stress compared to the salt susceptible cultivar NB. The differences in translational dynamics between NB and SR86 may derive from their differing levels of ribosome stalling under salt stress.


Assuntos
Oryza , Oryza/genética , Proteômica , Ribossomos/genética , Transcriptoma
5.
Development ; 145(17)2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-30093550

RESUMO

The cytoplasm of striated myofibers contains a large number of membrane organelles, including sarcoplasmic reticulum (SR), T-tubules and the nuclear membrane. These organelles maintain a characteristic juxtaposition that appears to be essential for efficient inter-membranous exchange of RNA, proteins and ions. We found that the membrane-associated Muscle-specific α2/δ (Ma2/d) subunit of the Ca2+ channel complex localizes to the SR and T-tubules, and accumulates at the myonuclear surfaces. Furthermore, Ma2/d mutant larval muscles exhibit nuclear positioning defects, disruption of the nuclear-SR juxtapositioning, as well as impaired larval locomotion. Ma2/d localization at the nuclear membrane depends on the proper function of the nesprin ortholog Msp300 and the BAR domain protein Amphiphysin (Amph). Importantly, live imaging of muscle contraction in intact Drosophila larvae indicated altered distribution of Sarco/Endoplamic Reticulum Ca2+-ATPase (SERCA) around the myonuclei of Ma2/d mutant larvae. Co-immunoprecipitation analysis supports association between Ma2/d and Amph, and indirectly with Msp300. We therefore suggest that Ma2/d, in association with Msp300 and Amph, mediates interactions between the SR and the nuclear membrane.


Assuntos
Transporte Biológico/fisiologia , Canais de Cálcio/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Miofibrilas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Membrana Nuclear/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Animais Geneticamente Modificados , Cálcio/metabolismo , Drosophila , Contração Muscular/fisiologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
6.
Mol Carcinog ; 60(4): 279-293, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33629774

RESUMO

Alternative splicing (AS) is a process that produces various mRNA splicing isoforms via different splicing patterns of mRNA precursors (pre-mRNAs). AS is the primary mechanism for increasing the types and quantities of proteins to improve biodiversity and influence multiple biological processes, including chromatin modification, signal transduction, and protein expression. It has been reported that AS is involved in the tumorigenesis and development of colorectal carcinoma (CRC). In this review, we delineate the concept, types, regulatory processes, and technical advances of AS and focus on the role of AS in CRC initiation, progression, treatment, and prognosis. This summary of the current knowledge about AS will contribute to our understanding of CRC initiation and development. This study will help in the discovery of novel biomarkers and therapeutic targets for CRC prognosis and treatment.


Assuntos
Processamento Alternativo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico
7.
BMC Surg ; 21(1): 137, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731072

RESUMO

BACKGROUND: To analyze whether neoadjuvant chemoradiotherapy (nCRT) could improve the survival for patients with adenocarcinoma of the esophagogastric junction compared with neoadjuvant chemotherapy (nCT). Both neoadjuvant chemotherapy alone and chemoradiotherapy before surgery have been shown to improve overall long-term survival for patients with adenocarcinoma in the esophagus or esophagogastric junction compared to surgery alone. It remains controversial whether nCRT is superior to nCT. METHODS: 170 Patients with locally advanced (cT3-4NxM0) Siewert II and III adenocarcinoma of the esophagogastric junction (AEG) were treated with neoadjuvant chemotherapy consisting of capecitabine plus oxaliplatin with or without concurrent radiotherapy in the Fourth Hospital of Hebei Medical University. Intensity-modulated radiation therapy (IMRT) was used and delivered in 5 daily fractions of 1.8 Gy per week for 5 weeks (total dose of PTV: 45 Gy). 120 Patients were included in the propensity score matching (PSM) analysis to compare the effects of nCRT with nCT on survival. RESULTS: With a median follow-up of 41.2 months for patients alive after propensity score matching analysis, the 1- and 3-year OS were 84.8%, 55.0% in nCRT group and 78.3%, 38.3% in nCT group (P = 0.040; HR = 1.65, 95% CI 1.02-2.69). The 1- and 3-year PFS were 84.9%, 49.2% in nCRT group and 68.3%, 29.0% in nCT group (P = 0.010; HR = 1.80, 95% CI 1.14-2.85). The pathological complete response (pCR) was 17.0% in nCRT group and 1.9% in nCT group (P = 0.030). No significant difference was observed in postoperative complications between the two groups. CONCLUSION: The nCRT confers a better survival with improved R0 resection rate and pCR rate compared with nCT for the patients with locally advanced AEG.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Taxa de Sobrevida
8.
J Nurs Manag ; 29(5): 1207-1219, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33480142

RESUMO

AIMS: To develop a model illustrating the factors that can influence care needs in daily living (CNDL) of older adults and the pathways between these. BACKGROUND: The care needs in community-dwelling older adults have increased sharply. A better understanding of the elderly's CNDL would thus help policymakers define which types of support and services should be given. METHODS: A multicentre study with structural equation modelling was conducted in this study. We recruited 3,448 community-dwelling older adults in China by using a stratified random cluster sampling technique. RESULTS: Physical and mental health was the strongest predictor of CNDL. Both age and living situation had positive effects on CNDL, while economic factors, social support and family support were the major risk factors for CNDL. CONCLUSION: The presented model provides a better understanding of how to address CNDL in the targeted population. The older adults who are the oldest, low-income, non-empty nesters, and with poor self-rated health or the signs of loneliness should be firstly targeted for daily assistance. IMPLICATIONS FOR NURSING MANAGEMENT: Using this model could provide health authorities and managers with the information of distinguishing between the priority group and the strategies for easing the caregiving burden in older adults care, and thus improving resource utilization.


Assuntos
Vida Independente , Saúde Mental , Idoso , China , Necessidades e Demandas de Serviços de Saúde , Humanos , Análise de Classes Latentes
9.
J Exp Biol ; 218(Pt 8): 1159-65, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25714570

RESUMO

The ability of many insects to walk on vertical smooth surfaces such as glass or even on the ceiling has fascinated biologists for a long time, and has led to the discovery of highly specialized adhesive organs located at the distal end of the animals' legs. So far, research has primarily focused on structural and ultrastructural investigations leading to a deeper understanding of adhesive organ functionality and to the development of new bioinspired materials. Genetic approaches, e.g. the analysis of mutants, to achieve a better understanding of adhesive organ differentiation have not been used so far. Here, we describe the first Drosophila melanogaster mutant that develops malformed adhesive organs, resulting in a complete loss of climbing ability on vertical smooth surfaces. Interestingly, these mutants fail to make close contact between the setal tips and the smooth surface, a crucial condition for wet adhesion mediated by capillary forces. Instead, these flies walk solely on their claws. Moreover, we were able to show that the mutation is caused by a P-element insertion into the Su(z)2 gene locus. Remobilization of the P-element restores climbing ability. Furthermore, we provide evidence that the P-element insertion results in an artificial Su(z)2 transcript, which most likely causes a gain-of-function mutation. We presume that this transcript causes deregulation of yet unknown target genes involved in pulvilli differentiation. Our results nicely demonstrate that the genetically treatable model organism Drosophila is highly suitable for future investigations on adhesive organ differentiation.


Assuntos
Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Proteínas Repressoras/fisiologia , Animais , Elementos de DNA Transponíveis , Proteínas de Drosophila/genética , Drosophila melanogaster/anatomia & histologia , Drosophila melanogaster/genética , Extremidades/anatomia & histologia , Extremidades/fisiologia , Locomoção , Mutação , Proteínas Repressoras/genética
10.
J Cell Sci ; 125(Pt 2): 461-72, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22302994

RESUMO

Here we report on the generation and in vivo analysis of a series of loss-of-function mutants for the Drosophila ArfGEF, Gartenzwerg. The Drosophila gene gartenzwerg (garz) encodes the orthologue of mammalian GBF1. garz is expressed ubiquitously in embryos with substantially higher abundance in cells forming diverse tubular structures such as salivary glands, trachea, proventriculus or hindgut. In the absence of functional Garz protein, the integrity of the Golgi complex is impaired. As a result, both vesicle transport of cargo proteins and directed apical membrane delivery are severely disrupted. Dysfunction of the Arf1-COPI machinery caused by a loss of Garz leads to perturbations in establishing a polarized epithelial architecture of tubular organs. Furthermore, insufficient apical transport of proteins and other membrane components causes incomplete luminal diameter expansion and deficiencies in extracellular matrix assembly. The fact that homologues of Garz are present in every annotated metazoan genome indicates that secretion processes mediated by the GBF-type ArfGEFs play a universal role in animal development.


Assuntos
Proteínas de Drosophila/fisiologia , Drosophila/embriologia , Fatores de Troca do Nucleotídeo Guanina/fisiologia , Via Secretória , Animais , Linhagem Celular , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Complexo de Golgi/metabolismo , Complexo de Golgi/ultraestrutura , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Mutação , Glândulas Salivares/embriologia , Glândulas Salivares/ultraestrutura , Traqueia/embriologia , Traqueia/metabolismo , Traqueia/ultraestrutura
11.
Biochem Biophys Res Commun ; 446(1): 417-22, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24613841

RESUMO

Soil salinity and alkalinity are common constraints to crop productivity in low rainfall regions of the world. However, the physiological difference of plant response to these two stresses was short of deep investigation. This study has identified a set of differentially expressed proteins of tomato root exploring to NaCl and NaHCO3 stress by iTRAQ (isobaric tags for relative and absolute quantitation) assay. A total of 313 proteins responsive to NaCl and NaHCO3 were observed. Among these proteins, 70 and 114 proteins were up-regulated by salt and alkali stress, respectively. While down-regulated proteins were 80 in salt treatment and 83 in alkali treatment. Only 39 up-regulated proteins and 30 down-regulated proteins were shared by salt and alkali stresses. The majority of the down-regulated proteins accounted for metabolism and energy conversion, and the up-regulated proteins were involved in signaling or transport. Compared with salt stress, alkali stress down-regulated proteins related with the respiratory metabolism, fatty acid oxidative metabolism and nitrogenous metabolism of tomato roots, and up-regulated protein with the reactive oxygen species (ROS) scavenging and ion transport. This study provides a novel insight into tomato roots response to salt and alkali stress at a large translation level.


Assuntos
Proteínas de Choque Térmico/metabolismo , Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/isolamento & purificação , Proteínas de Transporte/metabolismo , Cromatografia por Troca Iônica , Regulação para Baixo , Regulação da Expressão Gênica de Plantas , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/isolamento & purificação , Concentração de Íons de Hidrogênio , Solanum lycopersicum/genética , Pressão Osmótica , Proteínas de Plantas/genética , Proteínas de Plantas/isolamento & purificação , Raízes de Plantas/metabolismo , Proteoma/genética , Proteoma/isolamento & purificação , Proteoma/metabolismo , Proteômica/métodos , Espécies Reativas de Oxigênio/metabolismo , Salinidade , Tolerância ao Sal , Transdução de Sinais , Bicarbonato de Sódio , Solo/química , Espectrometria de Massas por Ionização por Electrospray , Estresse Fisiológico , Espectrometria de Massas em Tandem , Regulação para Cima
12.
Cancer Med ; 13(7): e7129, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618967

RESUMO

BACKGROUND: The RNA-binding motif single-stranded interacting protein 3 (RBMS3) is a constituent of the RNA-binding motif (RBM) protein family, which assumes a pivotal role in governing cellular biogenesis processes such as the cell cycle and apoptosis. Despite an abundance of studies elucidating RBMS3's divergent roles in the genesis and advancement of various tumors, its involvement in colon cancer remains enigmatic. METHODS: The present investigation employed data analysis from TCGA and GTEx to unveil that RBMS3 expression demonstrated a diminished presence in colon cancer tissues when juxtaposed with normal colon tissues. The effect of RBMS3 and LIM zinc finger domain 1 (LIMS1) on colon cancer was substantiated via animal models and cellular experiments. The connection between RBMS3 and LIM zinc finger domain 1 (LIMS1) was verified by molecular biology methods. RESULTS: The study conclusively ascertained that augmenting RBMS3 expression quells the proliferation, migration, and invasion of colon cancer cells. Furthermore, the inquiry unveiled a plausible mechanism through which RBMS3 impacts the expression of LIMS1 by modulating its mRNA stability. The investigation ascertained that RBMS3 inhibits the progression of colon cancer by regulating LIMS1. The inhibitory function of LIMS1 and RBMS3 is closely intertwined in colon cancer, with knocking down LIMS1 being able to rescue the inhibitory effect of RBMS3 overexpression on the functionality of colon cancer cell CONCLUSIONS: The discernments delineate RBMS3 as a novel suppressor of cancer via LIMS1, thereby bestowing fresh therapeutic possibilities and illuminating the intricacies of colon cancer.


Assuntos
Neoplasias do Colo , Animais , Apoptose , Ciclo Celular/genética , Neoplasias do Colo/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Humanos
13.
PeerJ ; 11: e16483, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107581

RESUMO

Background: O-methyltransferase (OMT)-mediated O-methylation is a frequent modification that occurs during natural product biosynthesis, and it increases the diversity and stability of secondary metabolites. However, detailed genome-wide identification and expression analyses of OMT gene family members have not been performed in melons. In this study, we aimed to perform the genome-wide identification of OMT gene family members in melon to identify and clarify their actions during stress. Methods: Genome-wide identification of OMT gene family members was performed using data from the melon genome database. The Cucumis melo OMT genes (CmOMTs) were then compared with the genes from two representative monocotyledons and three representative dicotyledons. The basic information, cis-regulatory elements in the promoter, predicted 3-D-structures, and GO enrichment results of the 21 CmOMTs were analyzed. Results: In our study, 21 CmOMTs (named CmOMT1-21) were obtained by analyzing the melon genome. These genes were located on six chromosomes and divided into three groups composed of nine, six, and six CmOMTs based on phylogenetic analysis. Gene structure and motif descriptions were similar within the same classes. Each CmOMT gene contains at least one cis-acting element associated with hormone transport regulation. Analysis of cis-acting elements illustrated the potential role of CmOMTs in developmental regulation and adaptations to various abiotic and biotic stresses. The RNA-seq and quantitative real-time PCR (qRT-PCR) results indicated that NaCl stress significantly induced CmOMT6/9/14/18 and chilling and high temperature and humidity (HTH) stresses significantly upregulated CmOMT14/18. Furthermore, the expression pattern of CmOMT18 may be associated with Fusarium oxysporum f. sp. melonis race 1.2 (FOM1.2) and powdery mildew resistance. Our study tentatively explored the biological functions of CmOMT genes in various stress regulation pathways and provided a conceptual basis for further detailed studies of the molecular mechanisms.


Assuntos
Cucumis melo , Cucumis melo/genética , Metiltransferases/genética , Filogenia , Genoma de Planta/genética , Estresse Fisiológico/genética
14.
Cancer Res ; 83(21): 3593-3610, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37560971

RESUMO

Many studies have provided valuable information about genomic and transcriptomic changes that occur in colorectal cancer. However, protein abundance cannot be reliably predicted by DNA alteration or mRNA expression, which can be partially attributed to posttranscriptional and/or translational regulation of gene expression. In this study, we identified increased translational efficiency (TE) as a hallmark of colorectal cancer by evaluating the transcriptomic and proteomic features of patients with colorectal cancer, along with comparative transcriptomic and ribosome-protected mRNA analysis in colon epithelial cells and colon cancer cells. COP9 signalosome subunit 7B (COPS7B) was among the key genes that consistently showed both significant TE increase and protein elevation without transcriptional alteration in colorectal cancer. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) enhanced the TE of COPS7B mRNA to promote colorectal cancer growth and metastasis. COPS7B was found to be a component of the ribo-interactome that interacted with ribosomes to facilitate ribosome biogenesis and mRNA translation initiation. Collectively, this study revealed the proteomic features of colorectal cancer and highlighted elevated mRNA translation as a hallmark of colorectal cancer. The identification of the IGF2BP3-COPS7B axis underlying the increased protein synthesis rate in colorectal cancer provided a promising therapeutic target to treat this aggressive disease. SIGNIFICANCE: Increased expression of COPS7B mediated by IGF2BP3 elevates the translational efficiency of genes enriched in mRNA translation and ribosome biogenesis pathways, promoting protein synthesis and driving progression in colorectal cancer.


Assuntos
Neoplasias do Colo , Proteômica , Humanos , Neoplasias do Colo/metabolismo , Biossíntese de Proteínas , Ribossomos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Complexo do Signalossomo COP9/metabolismo , Fatores de Transcrição/metabolismo
15.
Cancer Chemother Pharmacol ; 92(2): 83-95, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37335335

RESUMO

Aberrant alternative splicing (AS) events are frequently observed in lung cancer, which can be attributed to aberrant gene AS, alterations in splicing regulatory factors, or changes in splicing regulatory mechanisms. Consequently, the dysregulation of alternative RNA splicing is the fundamental cause of lung cancer. In this review, we have summarized the pivotal role of AS in the development, progression, invasion, metastasis, angiogenesis, and drug resistance of lung cancer. Ultimately, this review emphasizes the potential of AS as biomarkers in lung cancer prognosis and diagnosis, and introduces some applications of AS isoform in the treatment of lung cancer. The comprehension of the AS may provide a glimmer of hope for the eradication of lung cancer.


Assuntos
Processamento Alternativo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Fatores de Processamento de RNA/genética , Prognóstico , Biomarcadores , Regulação Neoplásica da Expressão Gênica
16.
Nat Commun ; 13(1): 2731, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585058

RESUMO

Biologically derived and biologically inspired fibers with outstanding mechanical properties have found attractive technical applications across diverse fields. Despite recent advances, few fibers can simultaneously possess high-extensibility and self-recovery properties especially under wet conditions. Here, we report protein-based fibers made from recombinant scallop byssal proteins with outstanding extensibility and self-recovery properties. We initially investigated the mechanical properties of the native byssal thread taken from scallop Chlamys farreri and reveal its high extensibility (327 ± 32%) that outperforms most natural biological fibers. Combining transcriptome and proteomics, we select the most abundant scallop byssal protein type 5-2 (Sbp5-2) in the thread region, and produce a recombinant protein consisting of 7 tandem repeat motifs (rTRM7) of the Sbp5-2 protein. Applying an organic solvent-enabled drawing process, we produce bio-inspired extensible rTRM7 fiber with high-extensibility (234 ± 35%) and self-recovery capability in wet condition, recapitulating the hierarchical structure and mechanical properties of the native scallop byssal thread. We further show that the mechanical properties of rTRM7 fiber are highly regulated by hydrogen bonding and intermolecular crosslinking formed through disulfide bond and metal-carboxyl coordination. With its outstanding mechanical properties, rTRM7 fiber can also be seamlessly integrated with graphene to create motion sensors and electrophysiological signal transmission electrode.


Assuntos
Pectinidae , Proteínas , Animais , Proteínas/química , Proteômica , Alimentos Marinhos , Software
17.
J Exp Clin Cancer Res ; 41(1): 67, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35180863

RESUMO

BACKGROUND: Epidemiological studies have confirmed that abnormal circadian rhythms are associated with tumorigenesis in breast cancer. However, few studies have investigated the pathological roles of rhythm genes in breast cancer progression. In this study, we aimed to evaluate the aberrant expression of 32 rhythm genes in breast cancer and detect the pathological roles and molecular mechanisms of the altered rhythm gene in regulating the progression of triple negative breast cancer (TNBC). METHODS: The aberrant expression of rhythm genes in breast cancer was screened by searching the GEPIA database and validated by using qRT-PCR and immunohistochemistry staining. Bioinformatics analysis combined with luciferase reporter experiment and chromatinimmunopercitation (ChIP) were used to investigate the molecular mechanism about aberrant expression of identified rhythm gene in breast cancer. The pathological roles of identified rhythm gene in TNBC progression was evaluated by colony formation assay, wound healing experiment, transwell assay, subcutaneous tumor formation and the mouse tail vein injection model through gain-of-function and loss-of-function strategies respectively. mRNA array, bioinformatics analysis, luciferase reporter experiment, ChIP and immunoflurescence assay were employed to investigate the key molecules and signaling pathways by which the identified rhythm gene regulating TNBC progression. RESULTS: We identified that nuclear factor interleukin 3 regulated (NFIL3) expression is significantly altered in TNBC compared with both normal breast tissues and other subtypes of breast cancer. We found that NFIL3 inhibits its own transcription, and thus, downregulated NFIL3 mRNA indicates high expression of NFIL3 protein in breast cancer. We demonstrated that NFIL3 promotes the proliferation and metastasis of TNBC cells in vitro and in vivo, and higher expression of NFIL3 is associated with poor prognosis of patients with TNBC. We further demonstrated that NFIL3 enhances the activity of NF-κB signaling. Mechanistically, we revealed that NFIL3 directly suppresses the transcription of NFKBIA, which blocks the activation of NF-κB and inhibits the progression of TNBC cells in vitro and in vivo. Moreover, we showed that enhancing NF-κB activity by repressing NFKBIA largely mimics the oncogenic effect of NFIL3 in TNBC, and anti-inflammatory strategies targeting NF-κB activity block the oncogenic roles of NFIL3 in TNBC. CONCLUSION: NFIL3 promotes the progression of TNBC by suppressing NFKBIA transcription and then enhancing NF-κB signaling-mediated cancer-associated inflammation. This study may provide a new target for TNBC prevention and therapy.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Inibidor de NF-kappaB alfa/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Transdução de Sinais
18.
Plant Sci ; 309: 110954, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34134849

RESUMO

Powdery mildew caused by Podosphaera xanthii (P. xanthii) severely endangers melon (Cucumis melo L.) production, while the mechanistic understanding about its resistance to powdery mildew remains largely limited. In this study, we integrated transcriptomic and methylomic analyses to explore whether DNA methylation was involved in modulating transcriptional acclimation of melon to P. xanthii infection. Net photosynthetic rate (Pn), stomatal conductance (Gs), actual photochemical efficiency (ФPSII) and maximum PSII quantum yield (Fv/Fm) were significantly decreased in P. xanthii-infected plants relative to uninfected ones (Control), revealing apparent physiological disorders. Totally 4808 differentially expressed genes (DEGs) were identified by global analysis of gene expression in Control and P. xanthii-infected plants. Comparative methylome uncovered that 932 DEGs were associated with hypermethylation, while 603 DEGs were associated with hypomethylation in melon upon P. xanthii infection. Among these differential methylation-involved DEGs, a set of resistance-related genes including R genes and candidate genes in metabolic and defense pathways were further identified, demonstrating that DNA methylation might function as a new regulatory layer for melon resistance to P. xanthii infection. Altogether our study sheds new insights into the molecular mechanisms of melon against powdery mildew and provides some potential targets for improving melon disease resistance in future.


Assuntos
Ascomicetos/fisiologia , Cucurbitaceae/genética , Epigenoma , Doenças das Plantas/imunologia , Cucurbitaceae/imunologia , Cucurbitaceae/microbiologia , Metilação de DNA , Doenças das Plantas/microbiologia
19.
J Med Imaging Radiat Oncol ; 65(6): 778-785, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34159731

RESUMO

INTRODUCTION: Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small cell lung cancer (LS-SCLC) who achieve good response after chemoradiotherapy. But PCI is neurotoxic. Magnetic resonance imaging (MRI) is the standard tool for evaluating brain metastasis (BM). This study was to retrospectively analyse the necessity of PCI in the era of MRI in LS-SCLC. METHODS: From July 2013 to June 2017, 190 patients with LS-SCLC who were treated with definitive chemoradiotherapy were included and analysed in this study. They were divided into the PCI group and non-PCI group. Propensity score matching (PSM) analysis was used to balance the variable differences. The Kaplan-Meier method was applied to estimate survival with log-rank test to ascertain significance between different groups. RESULTS: Seventy-seven patients (40.5%) received PCI after chemoradiotherapy. After adjustment for propensity scores, 69 pairs of patients were matched between two groups. After PSM, the 1-year and 3-year OS rates were 96.9% and 48.5% in PCI group versus 89.9% and 25.0% in non-PCI group (HR: 0.419, 95% CI: 0.251-0.701, P = 0.001). The 1-year and 3-year BMFS in PCI group were 96.8% and 67.5% versus 62.3% and 37.9% in non-PCI group (HR: 0.247, 95% CI: 0.132-0.460, P < 0.001). CONCLUSION: For patients showing no BM on MRI after definitive CRT, PCI confers less BM and better OS in LS-SCLC.


Assuntos
Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Imageamento por Ressonância Magnética , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/radioterapia
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 262: 120131, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34256239

RESUMO

Two novel fluorescent probes based on 7-hydroxy-4-methyl-coumarin, FAA-MC-OH (2-fluoro-4-nitro-phenylacetyl hydroxyl coumarin) and FBA-MC-OH (2-fluoro-4-nitro-benzoyl hydroxyl coumarin) are first synthesized, and spectral studies confirm that both the probes display highly selective and sensitive to H2O2, especially FBA-MC-OH has a shorter response time. Moreover, it is worth noting that the reaction mechanism is based on bi-nucleophilic substitution instead of oxidation or hydrolysis, which is different from previous reported probes'.


Assuntos
Peróxido de Hidrogênio , Radical Hidroxila , Corantes Fluorescentes , Oxirredução
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