RESUMO
Regulator of ribosome synthesis 1 (RRS1), a crucial regulatory factor in ribosome biogenesis, exerts a remarkable impact on the progression of breast cancer (BC). However, the exact mechanisms and pathways have not yet been fully elucidated. To investigate the impact of RRS1 on BC growth and metastasis, along with its underlying mechanisms. We discovered that RRS1 is overexpressed in BC tissues and cell lines. This study aims to regulate the level of RRS1 through lentiviral transfection technology to explore its potential function in BC cells. Knockdown of RRS1 resulted in the inhibition of cell proliferation, invasion, and migration, whereas overexpression had the opposite effects. We firstly identified the interaction between RRS1 and Glucose-Regulated Protein 78 (GRP78) using Co-immunoprecipitation (Co-IP) combined with mass spectrometry analysis, providing evidences of co-localization and positive regulation between RRS1 and GRP78. We observed that RRS1 inhibited the degradation of GRP78 through the ubiquitin-proteasome pathway, resulting in the stabilization of GRP78. In addition, our findings suggested that RRS1 promoted BC progression by activating the GRP78-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. In conclusion, this newly discovered RRS1/GRP78 signaling axis provides a molecular and theoretical basis for further exploring the mechanisms of breast cancer invasion and metastasis.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Chaperona BiP do Retículo Endoplasmático , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ribossomos/metabolismo , Proteínas de Ligação a RNARESUMO
OBJECTIVE: To explore the correlation between sleep duration and type II diabetes in adults. METHOD: Computer databases searches were carried out through October 1, 2022, including PubMed, Cochrane Library, Embase, and Web of Science. Relevant literature was collected, and the Newcastle-Ottawa Scale (NOS) and extracted data were used to exclude studies and evaluate quality on the basis of inclusion and exclusion criteria. Meta-analysis was conducted using RevMan 5.4.1 software with random/fixed effects models. RESULTS: A total of 5 studies with 74,226 subjects (31,611 in the male study group, 42,615 in the female study group) were included. The meta-analysis revealed that women with long sleep duration (LSD) have a higher risk for developing type II diabetes than men, OR = 0.70; 95% CI 0.59-0.84, Z = 4.00 and P < 0.001. Men with short sleep duration (SSD) tended to have a higher risk in developing type II diabetes than women though the difference between men and women did not reach statistical significance, OR = 1.09, 95% CI 0.73-1.62, Z = 0.42 and P = 0.68. Further subgroup analysis by regional populations suggested that men in Europe and America with SSD had a higher risk of type II diabetes OR = 1.52, 95% CI 1.04-2.21, Z = 2.18 and P = 0.03. CONCLUSION: Women with LSD may have a higher risk for type II diabetes, and men in Europe and America with SSD may have a higher risk for type II diabetes than men of other regions.
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Diabetes Mellitus Tipo 2 , Transtornos do Sono-Vigília , Humanos , Masculino , Adulto , Feminino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Fatores Sexuais , Duração do Sono , Europa (Continente)RESUMO
Many ribosomal proteins are highly expressed in tumors and are closely related to their diagnosis, prognosis and pathological characteristics. However, few studies are available on the correlation between ribosomal proteins and chemoresistance. RRS1 (human regulator of ribosome synthesis 1), a critical nuclear protein involved in ribosome biogenesis, also plays a key role in the genesis and development of breast cancer by protecting cancer cells from apoptosis. Given that apoptosis resistance is one of the causes of the cisplatin resistance of tumor cells, our aim was to determine the relationship between RRS1 and cisplatin resistance in breast cancer cells. Here, we report that RRS1 is associated with cisplatin resistance in breast cancer cells. RRS1 silencing increased the sensitivity of MCF-7/DDP cells to cisplatin and inhibited cancer cell proliferation by blocking cell cycle distribution and enhancing apoptosis. AEG-1 (astrocyte elevated gene-1) promotes drug resistance by interfering with the ubiquitination and proteasomal degradation of MDR1 (multidrug resistance gene 1), thereby enhancing drug efflux. We found that RRS1 binds to and stabilizes AEG-1 by inhibiting ubiquitination and subsequent proteasomal degradation, which then promotes drug efflux by upregulating MDR1. Furthermore, RRS1 also induces apoptosis resistance in breast cancer cells through the ERK/Bcl-2/BAX signaling pathway. Our study is the first to show that RRS1 sensitizes breast cancer cells to cisplatin by binding to AEG-1, and it provides a theoretical basis to improve the efficacy of cisplatin-based chemotherapy.
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Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Cisplatino/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Proteínas Ribossômicas , Ribossomos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos/farmacologia , Proteínas de Ligação a RNA/genéticaRESUMO
An increasing number of studies have indicated the crucial involvement of long non-coding RNAs (lncRNAs) in the onset and progression of malignancies. However, a complete understanding of the molecular mechanism underlying the effect of abnormally expressed lncRNAs on breast cancer (BC) remains elusive. This study aimed to elucidate the influence of the lncRNA small nucleolar RNA host gene 1 (SNHG1) on BC progression and its underlying mechanism. Our findings revealed a conspicuous up-regulation of SNHG1 in both BC tissues and cells. The downregulation of SNHG1 was observed to inhibit BC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) processes, while simultaneously promoting apoptosis. Furthermore, dual-luciferase reporter gene and RNA pull-down assays established that SNHG1 targeted miR-641 expression, while miR-641 targeted RRS1. Rescue studies demonstrated that in vitro SNHG1 silencing could be reversed by the miR-641 inhibitor, as well as by RRS1 upregulation. Moreover, in vivo downregulation of SNHG1 was found to inhibit BC growth. Through the inhibition of the miR-641 level, SNHG1 elevated the level of the downstream target RRS1, thereby fostering BC growth, migration, and invasion while inhibiting apoptosis. These findings suggest that SNHG1 may represent a potential therapeutic target for BC treatment.
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Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Feminino , Humanos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Processos Neoplásicos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismoRESUMO
Comparison of chemical composition and functional properties of insoluble and soluble dietary fiber (IDF, SDF) obtained from four China cereal brans was investigated. With findings, IDFs and SDFs for rice bran (RB), wheat bran (WB), highland barely bran (HBB) and tartary buckwheat bran (TBB) contained several monosaccharides such as arabinose, galactose, glucose, xylose, and galacturonic acid. The RBIDF was shrinking and formed a rugged microscopic structure, while the structure of WBIDF was dense and flat. HBBIDF and TBBIDF showed fold and flake structure. The glucose adsorption capacity of the HBBIDF was highest among all samples, which was 3.2 mmol/g. TBBIDF exhibited the highest value of cholesterol adsorption capacity (10.5 mg/g) at pH 7.0 and maximum binding capacity (BCmax, 365.2 µmol/g) for cadmium at pH 7.0 among all samples, respectively. As a result, HBBIDF and TBBIDF are potential fiber-rich ingredients in functional foods.
Assuntos
Fibras na Dieta , Grão Comestível , Fibras na Dieta/metabolismo , Grão Comestível/química , Adsorção , Alimento Funcional , GlucoseRESUMO
Background: Machine learning has shown to be an effective method for early prediction and intervention of Gestational diabetes mellitus (GDM), which greatly decreases GDM incidence, reduces maternal and infant complications and improves the prognosis. However, there is still much room for improvement in data quality, feature dimension, and accuracy. The contributions and mechanism explanations of clinical data at different pregnancy stages to the prediction accuracy are still lacking. More importantly, current models still face notable obstacles in practical applications due to the complex and diverse input features and difficulties in redeployment. As a result, a simple, practical but accurate enough model is urgently needed. Design and methods: In this study, 2309 samples from two public hospitals in Shenzhen, China were collected for analysis. Different algorithms were systematically compared to build a robust and stepwise prediction system (level A to C) based on advanced machine learning, and models under different levels were interpreted. Results: XGBoost reported the best performance with ACC of 0.922, 0.859 and 0.850, AUC of 0.974, 0.924 and 0.913 for the selected level A to C models in the test set, respectively. Tree-based feature importance and SHAP method successfully identified the commonly recognized risk factors, while indicated new inconsistent impact trends for GDM in different stages of pregnancy. Conclusion: A stepwise prediction system was successfully established. A practical tool that enables a quick prediction of GDM was released at https://github.com/ifyoungnet/MedGDM.This study is expected to provide a more detailed profiling of GDM risk and lay the foundation for the application of the model in practice.
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Amyloid-based nanostructures from food sources have been received intensive interests recently in material science, biomedicine and especially delivery system. This is due to the ability of protein-based amyloid architecture that proved to be an attractive system to carry drug and nutrition. However, few research focused on the modification of functional properties of different fractions isolated from amyloid fibrils. Hereby, we separated the retentate (RGFs) and filtrate (FGFs) fractions from rice glutelin fibrils (GFs) using centrifugal filtration and then investigated the structural characteristics and functional properties of these fractions. We proved that protein fibrillization would highly improve both emulsifying and antioxidant abilities of protein dispersion. In addition, further processed RGFs with rich ß-sheet structures exhibited a similar functional performance to GFs dispersion. By contrast, FGFs dispersion with less ß- sheet content, lower molecular weight, interestingly re-assembled into spherical aggregates with weaker interaction, exhibiting better antioxidant and emulsifying properties.
Assuntos
Nanoestruturas , Oryza , Amiloide/química , Antioxidantes/química , Glutens/química , Nanoestruturas/química , Oryza/químicaRESUMO
Regulator of ribosome synthesis 1 (RRS1) is a key factor in ribosome biosynthesis and other cellular functions. High level of RRS1 in breast cancer cell lines is associated with increased cell proliferation, invasion and migration. RRS1 controls the assembly of the 60s subunit and maturation of 25S rRNA during ribosome biosynthesis. In this study, lentiviral transfection of shRNA was used to knock down the level of RRS1, to detect the effect of RRS1 on cell function and to explore the specific mechanism of RRS1 affecting cell invasion and metastasis by COIP and dualluciferase reporter gene assays. The present study found that RRS1 knockdown reduced the accumulation of ribosome protein L11 (RPL11) in the nucleolus, which then migrated to the nucleoplasm and bound to cMyc. This inhibited transactivation of SNAIL by cMyc and eventually decreased the invasion and metastasis capacity of the human breast cancer cell line BT549. Taken together, RRS1 regulates invasion and metastasis of human breast cancer cells through the RPL11cMycSNAIL axis. The findings are of great significance for exploring the mechanism of breast cancer invasion and metastasis and the corresponding regulatory factors.
Assuntos
Regulação para Baixo/genética , Metástase Neoplásica/genética , Proteínas de Ligação a RNA/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Proliferação de Células/genética , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Regulação para Baixo/efeitos dos fármacos , Humanos , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/prevenção & controle , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Fatores de Transcrição da Família Snail/efeitos dos fármacos , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genéticaRESUMO
Objective: A meta-analysis is used to explore the relationship of sleep quality and duration with the risk of diabetic retinopathy (DR). Method: Cochrane Library, PubMed, Embase, and other databases are searched from their establishment to April 2022. Literature on the relationship of sleep quality and duration with DR risk published in various databases is collected, and two researchers independently screen the literature, extract data, and evaluate the quality of the included articles. The meta-analysis is performed with Review Manage 5.4.1 software. Results: A total of 7 articles are selected, including 4,626 subjects. The results show a strong correlation between sleep quality and DR risk. When comparing the sleep quality scores of "DR" (experimental group) and "NO DR" (control group), the Pittsburgh sleep quality index(PSQI) score of the DR group is significantly higher than that of the NO DR group (MD = 2.85; 95% confidence interval [CI] 1.92, 3.78, P<0.001), while the ESS score of the DR group is also significantly higher than that of the NO DR group (MD = 1.17; 95% confidence interval [CI] 0.14 to 2.30, P=0.04), so the sleep quality score of the DR group is higher than that of the NO DR group in both the PSQI and ESS scores, which confirms that low sleep quality is a risk factor for DR. Long sleep duration is also associated with the risk of developing DR; the number of adverse events (DR prevalence) is higher for "long sleep duration" than "normal sleep duration" [OR = 1.83, 95%CI 1.36-2.47, P < 0.001], suggesting that long sleep duration can cause increased DR risk. Short sleep duration is also associated with the occurrence of DR [OR = 1.49, 95%CI 1.15-1.94), P = 0.003] and can increase DR risk. Conclusion: Sleep quality and duration (including long and short sleep duration) are significantly associated with DR. To reduce DR risk, sleep intervention should be actively carried out, lifestyle changes should be made, and attention should be paid to the role of DR management.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Transtornos do Sono-Vigília , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Humanos , Fatores de Risco , Sono , Qualidade do SonoRESUMO
Objective: A meta-analysis is used to explore the relationship between polycystic ovary syndrome (PCOS) and the risk of Sleep disturbances. Method: Cochrane Library, PubMed, Embase, and Web of Science databases are searched by computer from their establishment to 1 May 2022. Review Manager 5.4 software is used for the meta-analysis. Results: A total of nine articles are included, with 1,107 subjects. The results show that PCOS is positively associated with the risk of Sleep disturbances. Comparing with the "PCOS group" (experimental group) with the "NON-PCOS group" (control group), the incidence of Sleep disturbances is higher (OR = 11.24, 95% CI: 2.00-63.10, Z = 2.75, p = 0.006); the Pittsburgh Sleep Quality Index (PSQI) scores of the PCOS group is higher than that of the NON-PCOS group (MD = 0.78, 95% CI: 0.32-1.25, Z = 3.30, p = 0.001); the Epworth Sleepiness Scale (ESS) scores of the PCOS group is higher than that of the NON-PCOS group (MD = 2.49, 95% CI: 0.80-4.18, Z = 2.88, p = 0.004); Apnea hypopnea index (AHIs) in the PCOS group are higher than those in the NON-PCOS group (MD = 2.68, 95% CI: 1.07-4.28, Z = 3.27, p = 0.001); the sleep efficiency of the PCOS group is lower than that of the NON-PCOS group (MD = -5.16, 95% CI: 9.39--0.93, Z = 2.39, p = 0.02); the sleep onset latency of the PCOS group is higher than that of the NON-PCOS group (MD = 2.45, 95% CI: 1.40-3.50, Z = 4.57, p < 0.001); and the Rapid Eyes Movement (REM) sleep in the PCOS group is higher than that in the NON-PCOS group (MD = 17.19, 95% CI: 11.62-55.76, Z = 6.05, p < 0.001). The studies included in each analysis have publication biases of different sizes. After subgroup analysis and sensitivity analysis, the heterogeneity of each study in the meta-analysis is reduced, the bias is reduced accordingly, and the stability of the results can be maintained. Conclusion: PCOS is positively associated with the risk of Sleep disturbances. In order to reduce such risk, attention should be paid to the role of PCOS management, and PCOS prevention and treatment should be actively carried out.
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Objective: The purpose of this meta-analysis is to systematically assess the effects of psychological intervention on empathy fatigue among nursing staff. Method: Five electronic databases are searched separately from their establishment to April 8th, 2022. The research team independently performs paper selection, quality assessment, data extraction and analysis for all included studies. PRISMA guidelines are used to report this meta-analysis. Results: A total of seven randomized controlled trials (RCTs) covering 513 nursing staff are included. The meta-analysis results show that the empathy fatigue score (SMD = -0.22, 95% CI: -0.42~-0.02, P = 0.03) and burnout (SMD = -0.37, 95% CI: -0.56~-0.19, P < 0.001) are lower than the control group. The empathy satisfaction score of the psychological intervention group is higher than that of the control group (SMD = 0.45, 95% CI: 0.27-0.63, P < 0.001). The differences are statistically significant (P < 0.05). Subgroup analysis finds significant heterogeneity in the impact of different departments on psychological intervention at ≥6 weeks (I 2 = 71%, P = 0.01) and <6 weeks (I 2 = 0%, P = 0.75) (P = 0.05). Different departments also show significant heterogeneity in the effects of psychological intervention: ICU (I 2 = 73%, P = 0.02), pediatric (I 2 = 53%, P = 0.14) and other departments (I 2 = 0%, P = 0.63). The differences are statistically significant (P = 0.0007). Besides, the results show that both mindfulness intervention (SMD = 0.50, 95% CI: 0.24-0.77, P = 0.0002) and other interventions (SMD = 0.41, 95% CI: 0.16-0.65, P = 0.001) are statistically significant difference in the level of empathy satisfaction between the psychological intervention group and the control group. Conclusion: Psychological intervention has a coordinated improvement effect on empathy fatigue, empathy satisfaction and burnout, and can also improve the quality of life of nursing staff.
Assuntos
Empatia , Intervenção Psicossocial , Humanos , Criança , Fadiga , Qualidade de VidaRESUMO
Objective: This study seeks to investigate the relationship between Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) and hearing impairment by meta-analysis. Methods: Cochrane Library, PubMed, Embase, Web of Science and other databases are searched from their establishment to July 1st, 2022. Literature on the relationship between OSAHS and hearing loss is collected, and two researchers independently perform screening, data extraction and quality evaluation on the included literature. Meta-analysis is performed using RevMan 5.4.1 software. According to the heterogeneity between studies, a random-effects model or fixed-effects model is used for meta-analysis. Results: A total of 10 articles are included, with 7,867 subjects, 1,832 in the OSAHS group and 6,035 in the control group. The meta-analysis shows that the incidence of hearing impairment in the OSAHS group is higher than in the control group (OR = 1.38; 95% CI 1.18-1.62, Z = 4.09, P < 0.001), and the average hearing threshold of OSAHS patients is higher than that of the control group (MD = 5.89; 95% CI 1.87-9.91, Z = 2.87, P = 0.004). After stratifying the included studies according to hearing frequency, the meta-analysis shows that the OSAHS group has a higher threshold of 0.25, and the response amplitudes at frequencies 2, 4, 6, and 8 kHz are all higher than those of the control group. Conclusion: Compared with the control group, the OSAHS group has a higher incidence of hearing loss, mainly high-frequency hearing loss. Thus, OSAHS is closely associated with and a risk factor for hearing loss.
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Studies of the EtOAc extract of the culture broth and methanol extract of the mycelium of Stereum insigne CGMCC5.57 led to the isolation of one new dihydrobenzofuran (1) and six known compounds (2-7). The structures of compounds were elucidated mainly by HRESIMS experiments, and 1D, 2D NMR spectroscopy analysis. This is the first report about the chemical constitutes of the fungus S. insigne.
Assuntos
Basidiomycota/química , Benzofuranos/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Antinematódeos/química , Antinematódeos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Benzaldeídos/farmacologia , Benzofuranos/química , Avaliação Pré-Clínica de Medicamentos/métodos , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Escherichia coli/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Micélio/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Pesticides, firmly attached to the topsoil, might enter nearby watercourses at periods with high erosive loss of sediments. Therefore, exposure of aquatic organisms to these low mobility pesticides, in many cases, will coincide with a high sediment concentration. In this study, both individual and combined effects of propiconazole and runoff sediment on the aquatic model bryophyte Vesicularia dubyana are studied. Individual exposure to propiconazole induced responses in V. dubyana at rather low concentration levels (approximately 1 microg/L), showing that harmful effects of propiconazole potentially may occur in watercourses draining propiconazole-treated fields. Individual exposure to the sediment size fractions S1 (0.16-2 microm) and S2 (0.03-0.16 microm) caused plant stress at a concentration of 100 mg/L. The coarser fraction S1 showed strong inhibition effects on photosynthesis, probably due to light attenuation. Compared to S1, the suspension with the finer fraction S2 showed lower turbidity, higher nutrient content, and a higher proportion of sediment-bound propiconazole. The combined effects of propiconazole and suspended sediment are dependent on concentrations of sediment and propiconazole. At low sediment concentration (e.g., 100 mg/L), neither S1 nor S2 reduce the toxicity of propiconazole, as only 2% of propiconazole are bound to particles. An increase in sediment concentration decreases the bioavailable concentration of propiconazole; however, at the same time, this increases the turbidity, thereby inhibiting plant photosynthesis.
Assuntos
Briófitas/metabolismo , Monitoramento Ambiental/métodos , Fungicidas Industriais/toxicidade , Plantas/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água , Adsorção , Agricultura , Carbono/química , Clorofila/química , Clorofila A , Relação Dose-Resposta a Droga , Sedimentos Geológicos , Cinética , Nitrogênio/química , Peroxidases/química , Fotossíntese , Chuva , Solo , Triazóis/química , Triazóis/farmacologia , ÁguaRESUMO
Sorption and desorption characteristics of propiconazole (1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole) to different particle/aggregate-size fractions of agricultural runoff material were investigated. Emphasis was put on clay and colloidal size fractions to evaluate their role as potential sorbents and carriers for this pesticide. The runoff material was separated into size fractions ranging from 2 mm to ca. 15 nm by wet sieving, sedimentation, centrifugation, and membrane ultrafiltration. Each fraction was characterized by its organic C content and C/N ratio. Distinctive sorption properties of clay-sized particles and colloids were investigated. The obtained size fractions differed significantly in their organic C concentration, C/N ratio, and sorption properties to propiconazole. Organic matter was mainly associated in aggregates >2 microm. Binding of propiconazole to this coarse fraction made up 80% of the sorbed propiconazole. The distribution coefficient between solid and aqueous phases increased with decreasing particle size. The colloidal fraction (<0.16 microm) exhibited the highest sorbtivity, with a distribution coefficient of 113 L kg(-1), which was more than four times higher than that in the bulk sample (27 L kg(-1)). The fraction <2 microm represented 8% of the total sample weight, but contributed to 20% of the sorbed propiconazole. Strong hysteresis was observed for the sorption-desorption of propiconazole on the runoff material. Under dilution very little sorbed propiconazole will be released into the water phase. Due to its high sorbtivity and mobility and the strong sorption-desorption hysteresis, particles in the fraction <2 microm can be important carriers of propiconazole in runoff suspensions with high sediment load.