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OBJECTIVES: Unexplained chronic cough (UCC) is common and has significant impacts on quality of life. Ongoing cough can sensitize the larynx, increasing the urge to cough and perpetuating the cycle of chronic cough. Vibrotactile stimulation (VTS) of the larynx is a noninvasive stimulation technique that can modulate laryngeal somatosensory and motor activity. Study objectives were to assess feasibility and acceptability of VTS use by people with UCC. Secondarily, changes in cough-related quality of life measures were assessed. METHODS: Adults with UCC recorded cough measures at baseline and after completing 2 weeks of daily VTS. Feasibility and acceptability were assessed through participant-reported device use and structured feedback. Cough-related quality of life measures were the Leicester Cough Questionnaire (LCQ) and the Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ). RESULTS: Nineteen adults participated, with mean age 67 years and cough duration 130 months. Notably, 93% of planned VTS sessions were logged, 94% of participants found the device comfortable to wear, 89% found it easy to operate and 79% would recommend it to others. Pre-post LCQ change achieved a minimal important difference (MID) (mean 1.3 [SD 2.4, p = 0.015]). NLHQ scores improved, but did not reach an MID. CONCLUSIONS: Laryngeal VTS use was feasible and acceptable for use by patients with UCC and was associated with a meaningful improvement in cough-related quality of life. Future studies will include VTS dose refinement and the inclusion of a comparison arm to further assess the potential for laryngeal VTS as a novel treatment modality for UCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
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Decoupling of crop-livestock systems increases the risks of pollution, waste of nutrient resources, and biodiversity loss. Crop-livestock integration (CLI) is an effective solution to these problems, and motivating farmers to adopt CLI is the key. Many countries have implemented environmental regulations (ER) aiming to influence farmers' CLI adoption decisions. Based on a field study of 316 hog farmers from Shaanxi Province of China, this paper applies the triple-hurdle model to empirically examine the impacts of economic expectations (EE) and ER on CLI adoption decisions. It also verifies the income effect of CLI. The results are as follows: 90.5% of farmers are willing to adopt CLI, but the adoption rate is only 40.8% and the average integration degree is only 0.236; CLI not been widely popularized. EE and ER promote farmers' CLI adoption significantly, while the impact of interaction between EE and ER on CLI adoption differs. IER weakens the positive impact of EE on farmers' CLI integration degree, which has a "crowding out effect." GER negatively moderates the impact of EE on farmers' adoption willingness of CLI. CER strengthens the positive effect of EE on farmers' adoption behavior and CLI integration degree. CLI increases the farmers' income. These results contribute to our understanding of the mechanisms of CLI adoption decisions and sustainable policy optimization for green agricultural development.
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Fazendeiros , China , Animais , Produtos Agrícolas , Gado , Agricultura , HumanosRESUMO
BACKGROUND: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals. OBJECTIVES: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD. METHODS: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale. RESULTS: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction. CONCLUSION: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects.
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Introduction: Rapid identification of infected individuals through viral RNA or antigen detection followed by effective personal isolation is usually the most effective way to prevent the spread of a newly emerging virus. Large-scale detection involves mass specimen collection and transportation. For biosafety reasons, denaturing viral transport medium has been extensively used during the SARS-CoV-2 pandemic. However, the high concentrations of guanidinium isothiocyanate (GITC) in such media have raised issues around sufficient GITC supply and laboratory safety. Moreover, there is a lack of denaturing transport media compatible with SARS-CoV-2 RNA and antigen detection. Methods: Here, we tested whether supplementing media containing low concentrations of GITC with ammonium sulfate (AS) would affect the throat-swab detection of SARS-CoV-2 or a viral inactivation assay targeting coronavirus and other enveloped and non-enveloped viruses. The effect of adding AS to the media on RNA stability and its compatibility with SARS-CoV-2 antigen detection were also tested. Results and discussion: We found that adding AS to the denaturing transport media reduced the need for high levels of GITC, improved SARS-COV-2 RNA detection without compromising virus inactivation, and enabled the denaturing transport media compatible with SARS-CoV-2 antigen detection.
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Importance: Unexplained chronic cough is common and has substantial negative quality-of-life implications, yet its causes are not well understood. A better understanding of how peripheral and central neural processes contribute to chronic cough is essential for treatment design. Objective: To determine if people with chronic cough exhibit signs of abnormal neural processing over laryngeal sensorimotor cortex during voluntary laryngeal motor activity such as vocalization. Design, Setting, and Participants: This was a cross-sectional study of a convenience sample of participants with chronic cough and healthy participants. Testing was performed in an acoustically and electromagnetically shielded chamber. In a single visit, electroencephalographic (EEG) signals were recorded from participants with chronic cough and healthy participants during voice production. The chronic cough group participants presented with unexplained cough of 8 weeks or longer duration with prior medical evaluation including negative results of chest imaging. None of the participants had a history of any neurologic disease known to impair vocalization or swallowing. Data collection for the healthy control group occurred from February 2 to June 28, 2018, and for the chronic cough group, from November 22, 2021, to June 21, 2022. Data analysis was performed from May 1 to October 30, 2022. Exposure: Participants with or without chronic cough. Main Outcome Measures: Event-related spectral perturbation over the laryngeal area of somatosensory-motor cortex from 0 to 30 Hz (ie, θ, α, and ß bands) and event-related coherence as a measure of synchronous activity between somatosensory and motor cortical regions. Results: The chronic cough group comprised 13 participants with chronic cough (mean [SD] age, 63.5 [7.8] years; 9 women and 4 men) and the control group, 10 healthy age-matched individuals (mean [SD] age, 60.3 [13.9] years; 6 women and 4 men). In the chronic cough group, the typical movement-related desynchronization over somatosensory-motor cortex during vocalization was significantly reduced across θ, α, and ß frequency bands when compared with the control group. Conclusions and Relevance: This cross-sectional study found that the typical movement-related suppression of brain oscillatory activity during vocalization is weak or absent in people with chronic cough. Thus, chronic cough affects sensorimotor cortical activity during the asymptomatic voluntary activation of laryngeal muscles.
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Córtex Motor , Voz , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Adolescente , Córtex Motor/fisiologia , Tosse , Estudos Transversais , Voz/fisiologia , Músculos LaríngeosRESUMO
BACKGROUND: Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology. METHODS: Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation. RESULTS: A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics. CONCLUSION: This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.
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Orthosiphon , Extratos Vegetais , Extratos Vegetais/farmacologia , Orthosiphon/química , Simulação de Acoplamento MolecularRESUMO
Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.
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Artrite Gotosa , Medicamentos de Ervas Chinesas , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Medicamentos de Ervas Chinesas/química , Controle de QualidadeRESUMO
Accurately assessing the impact of low-carbon urban construction on green economic development has great significance for achieving economic development with environmental protection, and for building an ecological civilization and a beautiful China. Based on panel data for 271 cities in China from 2004 to 2019, multi-period and spatial difference-in-difference econometric models were used to comprehensively investigate the impact of three batches of low-carbon city pilot policies on green economic development, finding the following: The contribution of low-carbon urban construction on urban green economic development is significant and positive, and still holds under a series of robustness tests. Parallel trend tests also show a lag in the policy effect, and the effect is strengthened over policy implementation time. Green orientation of technological progress, green transformation of industry, and green upgrade of consumption are important channels for the effect of the policies. The promotion effect of low-carbon city construction is stronger in the central and northern cities, and in cities with high green economic development, than in western and southern cities, and those with low green economic development. Construction of low-carbon pilot cities not only promotes their own green economic development, but also that in neighboring cities, exerting a demonstration effect. This effect is greater in urban areas. This study provides empirical support for policy planning to promote low-carbon urban construction across the country.
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Carbono , Desenvolvimento Econômico , Cidades , China , PolíticasRESUMO
Dysregulation of microRNAs (miRNAs or miRs) is implicated in the development of gastric cancer (GC), which is possibly related to their roles in targeting tumor-suppressive or tumor-promoting genes. Herein, the current study was intended to ascertain the function of miR-488 and its modulatory mechanism in GC. Initially, human GC cells were assayed for their in vitro malignancy after miRNA gain- or loss-of-function and RNA interference or overexpression. Also, tumorigenesis and liver metastasis were evaluated in nude mouse models. Results demonstrated that miR-488 elevation suppressed GC (MKN-45 and OCUM-1) cell proliferation, migration, and invasiveness in vitro and reduced their tumorigenesis and liver metastasis in vivo. The luciferase assay identified that miR-488 bound to HULC and inhibited its expression. Furthermore, HULC could enhance EZH2-H3K27me3 enrichment at the p53 promoter region and epigenetically repress the p53 expression based on the data from RIP- and ChIP-qPCR assay. Additionally, HULC was validated to enhance GC growth and metastasis in vitro and in vivo. Overall, HULC re-expression elicited by miR-488 inhibition can enhance EZH2-H3K27me3 enrichment in the p53 promoter and repress the p53 expression, thus promoting the growth and metastasis of GC.
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MicroRNAs , Neoplasias Gástricas , Animais , Humanos , Camundongos , Carcinogênese , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas , Neoplasias Hepáticas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
Finger position sense is a proprioceptive modality highly important for fine motor control. Its developmental time course is largely unknown. This cross-sectional study examined its typical development in 138 children (8-17 years) and a group of 14 healthy young adults using a fast and novel psychophysical test that yielded objective measures of position sense acuity. Participants placed their hands underneath a computer tablet and judged the perceived position of their unseen index finger relative to two visible areas displayed on a tablet following a two-forced-choice paradigm. Responses were fitted to a psychometric acuity function from which the difference between the point-of-subjective-equality and the veridical finger position (ΔPSE) was derived as a measure of position sense bias, and the uncertainty area (UA) as a measure of precision. The main results are: First, children under 12 exhibited a significantly greater UA than adults while adolescent children (13-17 years) exhibited no significant differences when compared to adults. Second, no significant age-related differences in ΔPSE were found across the age range of 8-17 years. This implies that the typical development of finger position sense from late childhood to adulthood is characterized as an age-dependent increase in proprioceptive precision and not as a decrease in bias.
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Dedos , Extremidade Superior , Adulto Jovem , Humanos , Criança , Adolescente , Estudos Transversais , Dedos/fisiologia , Extremidade Superior/fisiologia , Propriocepção/fisiologia , MãosRESUMO
Immune checkpoint inhibitors (ICIs) improve overall survival in patients with advanced gastric cancer (GC). However, the molecular characterization of GC in ICIs responders is unclear. A total of 288 advanced GC patients were included in this study. Next-generation sequencing analysis was performed on tumor tissue and paired blood to screen for somatic mutants in 639 tumor-associated genes. We demonstrated that ARID1A, HER2/3/4, KMT2C/2D, LRP1B, PIK3CA, SPTA1, and TP53 mutations were significantly correlated with high tumor mutation burden (TMB) score, as well as HER2 amplification. For HER2 and PIK3CA mutations types, this relationship was statistically significant with age and TP53 mutation status, which was also found in the CDH1 gene. These results were confirmed by sequencing 873 GC cases in the cBioPortal database. PIK3CA mutations appear to be associated with longer survival in elderly population and TP53 mutant subtypes. For the first time, we found that GC patients ≥60 years old or with TP53 mutated type and PIK3CA mutations were associated with higher TMB and better ICI response. Building upon the age and TP53 mutation status, this study suggested a novel stratification approach to GC patients and explored the correlations between genetic somatic mutations and TMB score.
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Neoplasias Gástricas , Humanos , Idoso , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/genética , Biomarcadores Tumorais/genética , Mutação , Classe I de Fosfatidilinositol 3-Quinases/genética , ImunoterapiaRESUMO
Although the spin Hall effect provides a pathway for efficient and fast current-induced manipulation of magnetization, application of spin-orbit torque magnetic random access memory with low power dissipation is still limited to spin Hall materials with low spin Hall angles or very high resistivities. This work reports a group of spin Hall materials, Pt1 -x (TiO2 )x nanocomposites, that combines a giant spin Hall effect with a low resistivity. The spin Hall angle of Pt1 -x (TiO2 )x in an yttrium iron garnet/Pt1 -x (TiO2 )x double-layer heterostructure is estimated from a combination of ferromagnetic resonance, spin pumping, and inverse spin Hall experiments. A giant spin Hall angle 1.607 ± 0.04 is obtained in a Pt0.94 (TiO2 )0.06 nanocomposite film, which is an increase by an order of magnitude compared with 0.051 ± 0.002 in pure Pt thin film under the same conditions. The great enhancement of spin Hall angle is attributed to strong side-jump induced by TiO2 impurities. These findings provide a new nanocomposite spin Hall material combining a giant spin Hall angle, low resistivity and excellent process compatibility with semiconductors for developing highly efficiency current-induced magnetization switching memory devices and logic devices.
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Tumor protein D52-like 2 or simply TPD52L2 belongs to the TPD52 family which has been implicated in a variety of human carcinomas. However, the TPD52L2 function in the gastric carcinoma oxaliplatin (OXA) resistance remains elusive. The main objective of this study is to evaluate the TPD52L2 effect in OXA-resistant gastric carcinoma cells in vitro. Oxaliplatin-resistant gastric carcinoma cells were generated in MGC-803 and SGC-7901 cells. siRNA-mediated knockdown of TPD52L2 was investigated in OXA-resistant MGC-803-OXA and SGC-7901-OXA cells. qRT-PCR was performed to assess the expression level of TPD52L2 mRNA. TPD52L2 protein expression level, apoptosis, and endoplasmic reticulum (ER) stress-associated proteins were identified via immunoblotting analysis. MTT assay was conducted for the evaluation of cell viability, while colony-forming activity was carried out via crystal violet staining. SGC-7901-OXA and MGC-803-OXA cells were found to be more resistant to OXA, as compared to the parental cell lines. The expression of TPD52L2 was found to be upregulated in OXA-resistant cells. Knockdown of TPD52L2 suppressed cell colony-forming potency, cell growth, and development in OXA-resistant cells. TPD52L2 knockdown also enhanced the PARP and caspase-3 cleavage. ER-associated proteins such as PERK, GRP78, CHOP, and IRE1α were found to be elevated in TPD52L2 knockdown cells. ER stress might be involved in TPD52L2 knockdown-induced apoptosis in OXA-resistant gastric carcinoma cells.
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Hand, foot, and mouth disease (HFMD) is a highly contagious disease in children caused by a group of enteroviruses. HFMD currently presents a major threat to infants and young children because of a lack of antiviral drugs in clinical practice. Drug repositioning is an attractive drug discovery strategy aimed at identifying and developing new drugs for diseases. Notably, repositioning of well-characterized therapeutics, including either approved or investigational drugs, is becoming a potential strategy to identify new treatments for virus infections. Various types of drugs, including antibacterial, cardiovascular, and anticancer agents, have been studied in relation to their therapeutic potential to treat HFMD. In this review, we summarize the major outbreaks of HFMD and the progress in drug repositioning to treat this disease. We also discuss the structural features and mode of action of these repositioned drugs and highlight the opportunities and challenges of drug repositioning for HFMD.
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Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Criança , Lactente , Humanos , Pré-Escolar , Doença de Mão, Pé e Boca/tratamento farmacológico , Doença de Mão, Pé e Boca/epidemiologia , Reposicionamento de Medicamentos , Surtos de Doenças , China/epidemiologiaRESUMO
Autophagy has an important role in regulating tumor cell survival. However, the roles of autophagy-related genes (ARGs) during colon adenocarcinoma (COAD) progression and their prognostic value have remained elusive. The present study aimed to identify the correlation between ARGs and the progression of COAD, as well as the prognostic significance of ARGs. The transcriptome proï¬les and the corresponding clinicopathological information of patients with COAD were downloaded from The Cancer Genome Atlas and Genotype-Tissue Expression databases. A list of ARGs was obtained from the Human Autophagy Database and bioinformatics analysis was performed to investigate the functions of these ARGs. Statistical analyses of these genes were performed to identify independent prognostic markers. The selected prognostic markers were then validated in 15 patients with COAD via immunohistochemistry. Differentially expressed ARGs between normal and tumor tissues were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the differentially expressed ARGs were mainly enriched in toxoplasmosis and pathways in cancer. The ATG4B, DAPK1 and SERPINA1 genes were determined to be associated with COAD progression. In addition, a risk signature was proposed that may serve as an independent prognostic marker. In conclusion, ATG4B, DAPK1 and SERPINA1 are crucial participants in tumorigenesis of COAD. The present study may promote the development of novel treatment strategies for COAD.
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Circular RNA is a kind of RNA with a covalently closed loop, which has a complex ability to modulate genes in the process of tumorigenesis and metastasis. Nevertheless, how circular RNA functions in gastric cancer (GC) remains unclear. The effect of circHIPK3 in vitro was studied here. Quantitative real-time PCR (qRT-PCR) was employed to found that circHIPK3 markedly increased in GC tissues and cell lines. And low expression of circHIPK3 suppressed the GC cells growing and metabolizing. Then the bioinformatics tool predicted the downstream target of circHIPK3, and it was proved by the dual-luciferase report experiment. According to the results of bioinformatics analysis and experimental data, it was clarified that circHIPK3 acted as a sponge of miR-637, releasing its direct target AKT1. The dual-luciferase assay revealed that mir-637 could bind circHIPK3 and AKT1. qRT-PCR data indicated that overexpression circHIPK3 led to the low level of miR-637 and overexpressed miR-637 would reduce AKT1 level. Finally, we demonstrated that the low expression of miR-637 or overexpression of AKT1 could attenuate the anti-proliferative effects of si-circHIPK3. These results suggest that the circHIPK3/miR-637/AKT1 regulatory pathway may be associated with the oncogene and growth of gastric cancer. In short, a new circular RNA circHIPK3 and its function are identified, and the regulatory pathway of circHIPK3/miR-637/AKT1 in the tumorigenesis and development of gastric cancer is discovered.
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Gastric cancer (GC) remains one of the most frequent cancers worldwide. Previous studies have shown that E3 ubiquitin ligase E3C (UBE3C) promotes the progression of multiple types of cancer. However, little is known about the expression and molecular mechanism of UBE3C in GC. In this study, UBE3C is upregulated in clinical GC samples and RNA-seq data from The Cancer Genome Atlas, and the UBE3C upregulation is correlated with poor clinical outcomes in patients with GC. In vitro, knockdown of UBE3C suppresses proliferation and enhances apoptosis in GC cells by inhibiting ß-catenin signaling pathway. In contrast, in vitro overexpression of UBE3C promotes GC cell proliferation and inhibits apoptosis through the upregulation of ß-catenin signaling by promoting ubiquitination of AXIN1. In vivo, knockdown of UBE3C inhibits tumor growth in a nude mouse model. Concurrently, the UBE3C knockdown resulted in an increase of AXIN1 and a reduction of ß-catenin in the nucleus and cytoplasm in the xenograft tumor tissues. Our results demonstrate that UBE3C promotes GC progression through activating the ß-catenin signaling via degradation of AXIN1. Our data suggest that UBE3C exerts oncogenic effects in GC and thus provides a promising prognostic biomarker and a potential therapeutic target for GC therapy.
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Proteína Axina/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/metabolismo , beta Catenina/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Citoplasma/metabolismo , Conjuntos de Dados como Assunto , Progressão da Doença , Feminino , Gastrectomia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteólise , RNA-Seq , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Regulação para Cima , Via de Sinalização Wnt , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: What is the optimal neoadjuvant chemotherapy (NAC) regimen for locally advanced gastric cancer (LAGC) remains debatable. The objective of this study was to compare the efficacy of docetaxel+oxaliplatin+S-1 (DOS) vs oxaliplatin+S-1 (SOX) as NAC for LAGC. METHODS: Data of 248 LAGC patients who received either DOS or SOX as NAC in our hospital between January 2010 and January 2018 were reviewed retrospectively. Propensity score matched (PSM) analysis was applied to minimize the selection bias in both groups. Prognostic factors were screened by univariate and multivariate Cox regression analyses. RESULTS: Of the 248 LAGC patients included, 180 patients were subjected to the PSM analysis. Patients in DOS group showed a better tumor response to NAC, higher radical resection rate and R0 resection rate than those in SOX group. The overall survival (OS) rate in DOS group was better than that in SOX group, although the overall incidence of Grade 3/4 NAC-related toxicity in DOS group was higher, as represented by leukopenia and neutropenia. Multivariate analysis revealed that the NAC regimen, cTNM stage and the R0 resection rate were independent prognostic factors. In addition, patients with TLND less than 16 population showed a worse OS rate. Subgroup analysis indicated that patients benefited from the addition of docetaxel regardless of the clinical T stage, but those with high clinical N stages (N2-3) did not. CONCLUSION: DOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.
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INTRODUCTION: It is worldwide accepted that lncRNA PTCSC3 is a tumor suppressor in glioma and thyroid cancer, whereas its role in the recurrence of gastric cancer is unknown. PATIENTS AND METHODS: We recruited 80 GC patients (46 males and 34 females, 44 to 68 years, 56.3±6.7 years) in our study. Two human GC cell lines AGS and SNU-1 were transfected with PTCSC3 and HOXA11-AS expression vectors. Then, qPCR was used to detect the level of relative mRNA. Both invasion and migration assays were performed to detect the effect of the lncRNA on gastric cancer cell motility. RESULTS: In the present study, we showed that PTCSC3 was downregulated in plasma of gastric cancer patients than in plasma of healthy controls. Follow-up study indicated that PTCSC3 was further downregulated in patients with distant-recurrence but not in patients with local recurrence only or non-recurrence. LncRNA HOXA11-AS was upregulated in plasma of gastric cancer cells than in plasma of healthy controls and was inversely correlated with PTCSC3 in plasma of gastric cancer patients. PTCSC3 overexpression mediated the downregulation of HOXA11-AS in gastric cancer cells, while HOXA11-AS overexpression failed to significantly affect PTCSC3. PTCSC3 overexpression led to inhibited, while HOXA11-AS overexpression led to promoted migration and invasion of gastric cancer cells. In addition, HOXA11-AS overexpression reduced the effects of PTCSC3 overexpression. DISCUSSION: Therefore, lncRNA PTCSC3 alleviates in the postoperative distant recurrence of gastric cancer possible by suppression of HOXA11-AS.
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Altered expression of family with sequence similarity 84, member B (FAM84B) has been found in various human cancers. However, the expression and function of FAM84B in pancreatic ductal adenocarcinoma (PDAC) has not been studied. Here, by analyzing The Cancer Genome Atlas cohort, we found that FAM84B amplification was observed in 11% of 141 PDAC patients, and FAM84B amplification was correlated with higher mRNA expression of FAM84B. FAM84B amplification and overexpression was significantly correlated with poor overall survival. Moreover, knockdown of FAM84B in PDAC cell lines suppressed cell proliferation and induced apoptosis. FAM84B knockdown also suppressed mitochondrial function and glycolysis of PDAC cells. Interestingly, knockdown of FAM84B decreased the nuclear accumulation of ß-catenin, and the expression of c-Myc and lactate dehydrogenase A, but enhanced the expression of Survivin. On the contrary, FAM84B overexpression displayed reversed effects in cell proliferation, apoptosis, mitochondrial function, and glycolysis, which was blocked by the Wnt/ß-catenin pathway inhibitor (XAV939). In addition, PDAC cells with lower expression of FAM84B were more sensitive to gemcitabine-induced cell proliferation inhibition both in vitro and in vivo. In conclusion, FAM84B plays an important role in aerobic glycolysis and tumorigenesis in PDAC and Wnt/ß-catenin may be involved in this process.