RESUMEN
Tamoxifen is a widely used antiestrogen drug in the endocrine therapy of breast cancer (BC). It blocks estrogen signaling by competitively binding to estrogen receptor α (ERα), thereby inhibiting the growth of BC cells. However, with the longterm application of tamoxifen, a subset of patients with BC have shown resistance to tamoxifen, which leads to low overall survival and progressionfree survival. The molecular mechanism of resistance is mainly due to downregulation of ERα expression and abnormal activation of the PI3K/AKT/mTOR signaling pathway. Moreover, the downregulation of targeted gene expression mediated by DNA methylation is an important regulatory mode to control protein expression. In the present review, methylation and tamoxifen are briefly introduced, followed by a focus on the effect of methylation on tamoxifen resistance and sensitivity. Finally, the clinical application of methylation for tamoxifen is described, including its use as a prognostic indicator. Finally, it is hypothesized that when methylation is used in combination with tamoxifen, it could recover the resistance of tamoxifen.
Asunto(s)
Neoplasias de la Mama , Metilación de ADN , Resistencia a Antineoplásicos , Tamoxifeno , Humanos , Tamoxifeno/uso terapéutico , Tamoxifeno/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Metilación de ADN/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/farmacología , Transducción de Señal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/genéticaRESUMEN
Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5â¯% O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.
RESUMEN
Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack of effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating mitochondrial injury. C57BL/6 mice were exposed to 20 Gy of lung irradiation (IR) and received daily intraperitoneal injections of MOTS-c for 2 weeks. MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by radiation. Meanwhile, MOTS-c reversed the apoptosis and mitochondrial damage of alveolar epithelial cells in RP mice. Furthermore, MOTS-c significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells and primary mouse lung epithelial cells. Mechanistically, MOTS-c increased the nuclear factor erythroid 2-related factor (Nrf2) level and promoted its nuclear translocation. Notably, Nrf2 deficiency abolished the protective function of MOTS-c in mice with RP. In conclusion, MOTS-c alleviates RP by protecting mitochondrial function through an Nrf2-dependent mechanism, indicating that MOTS-c may be a novel potential protective agent against RP.
RESUMEN
Background: Sugar-sweetened beverages (SSBs) and duration of physical exercise are strongly associated with physical health. Unfortunately, there are few studies focused on the association with psychological symptoms, let alone Tibetan university students at high altitudes in China. Methods: A stratified cluster sampling method was used to include 8,268 Tibetan university students aged 19-22 years in Qinghai and Tibet, both of which are high-altitude regions of China. Self-assessment questionnaires on SSBs, duration of physical exercise, and psychological symptoms were administered. The chi-square test and logistic regression analysis were used to analyze the associations among them. Results: The detection rate of psychological symptoms among Tibetan university students in high-altitude areas of China was 16.7%, with in girls (18.2%) higher than that in boys (14.8%), and the difference was statistically significant (χ2 = 11.73, p < 0.01). The proportion of SSBs for university students ≤1 time/week, 2-5 times/week, and ≥ 6 times/week were 54.2, 24.3, and 21.5%, respectively. The proportion of duration of physical exercise for >60 min/d was only 5.4%. Logistic regression analysis showed that compared with the SSBs ≤1 time/week group of university students, SSBs 2-5 times/week (OR = 1.45, 95% CI: 1.24-1.70) and ≥ 6 times/week (OR = 3.06, 95% CI: 2.62-3.57) had an increased risk of psychological symptoms (p < 0.001). In the reference group, the risk of psychological symptoms was also significantly increased in the group of university students with duration of physical exercise >60 min/d (OR = 2.08, 95% CI: 1.48-2.93), and the risk of psychological symptoms was also significantly increased in the group with duration of physical exercise <30 min/d (OR = 2.08, 95% CI: 1.48-2.93). The risk of psychological symptoms was also significantly increased in the university students with the duration of physical exercise <30 min/d (OR = 2.08, 95% CI: 1.48 ~ 2.93) group. Conclusion: SSBs and exercise time may be important influences on the psychological symptoms of Tibetan university students at high altitudes in China. This study has important implications for mental health planning in universities in highland areas and may also provide guidance for mental health interventions for Tibetan university students.
RESUMEN
BACKGROUND: The association of soyfoods or soybean products with executive functions in the brain has been less well studied. In this study, we investigated the consumption of soyfoods or soybean products and its association with executive functions in Chinese adolescents. METHODS: A three-stage stratified whole group sampling method was used to investigate the consumption of soyfoods or soybean products and executive functions among 1643 Chinese adolescents aged 13-15 years. One-way ANOVA and chi-square test were used to compare the basic conditions and executive functions of adolescents with different soyfoods or soybean products consumption. Linear regression analysis and logistic regression analysis were used to analyze the association between soyfoods or soybean products and executive functions. RESULTS: The proportions of Chinese adolescents with soyfoods or soybean products consumption ≤0 time/week, 1-3 time/week, and ≥4 time/week were 41.14 %, 46.80 %, and 12.05 %, respectively. Logistic regression analysis showed that with adolescents with soyfoods or soybean products consumption ≥4 time/week as a reference, adolescents with ≤0 time/week were less likely to have executive dysfunction in inhibiting functional (OR = 17.523, 95 % CI: 7.501, 40.938), 2back (OR = 3.384, 95 % CI: 1.729, 6.623), and switching functional (OR = 7.846, 95 % CI: 3.300, 18.657), were at higher risk of executive dysfunction (P < 0.001). CONCLUSION: Chinese adolescents' consumption of soyfoods or soybean products is inadequate and has a positive association with executive functions. The consumption of soyfoods or soybean products among Chinese adolescents should be increased in the future.
Asunto(s)
Función Ejecutiva , Alimentos de Soja , Humanos , Adolescente , Función Ejecutiva/fisiología , Masculino , Femenino , Estudios Transversales , China , Glycine max , Pueblos del Este de AsiaRESUMEN
Quercetin, a bioactive natural compound renowned for its potent anti-inflammatory, antioxidant, and antiviral properties, has exhibited therapeutic potential in various diseases. Given that bronchopulmonary dysplasia (BPD) development is closely linked to inflammation and oxidative stress, and quercetin, a robust antioxidant known to activate NRF2 and influence the ferroptosis pathway, offers promise for a wide range of age groups. Nonetheless, the specific role of quercetin in BPD remains largely unexplored. This study aims to uncover the target role of quercetin in BPD through a combination of network pharmacology, molecular docking, computer analyses, and experimental evaluations.
Asunto(s)
Displasia Broncopulmonar , Ferroptosis , Hiperoxia , Animales , Recién Nacido , Humanos , Displasia Broncopulmonar/tratamiento farmacológico , Displasia Broncopulmonar/metabolismo , Hiperoxia/tratamiento farmacológico , Hiperoxia/metabolismo , Quercetina/farmacología , Quercetina/uso terapéutico , Simulación del Acoplamiento Molecular , Ciclooxigenasa 2 , Animales Recién Nacidos , Antioxidantes , Farmacología en RedRESUMEN
Suicide among college students is a challenging problem globally. Yet, the association between sleep quality, depressive symptoms, and suicidal ideation remains unclear. This study aims to understand if depressive symptoms mediate the relationship between sleep quality and suicide ideation and whether the interaction between depressive symptoms and sleep quality on suicidal ideation is additive. A total of 1182 college students were recruited, and sleep quality, depressive symptoms, and suicidal ideation were assessed using questionnaires. Univariate analysis, logistic regression analysis, linear regression models, and the Sobel test were performed. The results showed that, among college students, poor sleep quality was positively associated with suicidal ideation, and the association was mediated through depressive symptoms. Moreover, there was a significant additive interaction between poor sleep quality and depressive symptoms on suicidal ideation. These findings suggest that, in the process of preventing and treating suicidal ideation in college students with sleep disorders, we should focus on the evaluation and intervention of depressive symptoms and adopt multidisciplinary team interventions for college students with sleep disorders and depression.
RESUMEN
BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.
Asunto(s)
Displasia Broncopulmonar , Hiperoxia , Lesión Pulmonar , Animales , Humanos , Recién Nacido , Ratones , Animales Recién Nacidos , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/metabolismo , Modelos Animales de Enfermedad , Células Endoteliales/patología , Hiperoxia/metabolismo , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Pulmón/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Lesión Pulmonar/prevención & control , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , ARN Mensajero/metabolismoRESUMEN
Land use competition among economic development, food security and ecological protection posed challenges for the sustainable development in resource-based cities, especially those represented by coal resource-based cities in China. Predicting future land use change under the coupled framework of shared socioeconomic pathways and representative concentration pathways (SSP-RCPs) was a crucial step in devising sustainable development strategies. In this study, the patch-generated land use simulation (PLUS) model coupled with SSP-RCP scenarios (SSP126, SSP245, SSP585) was used to predict land use changes from year 2020 to 2060, identify key management regions for balancing the goals of ecological protection and food security, and propose corresponding measures. The results showed that, (1) the selected driving factors and model parameters effectively simulated land use changes with an Overall accuracy of 0.95, a Kappa coefficient of 0.92, a Figure of Merit of 0.16, an Exchange error ≤5.69 %, a Shift error ≤1.04 %, and a Quantity error ≤0.67 %. (2) All the scenarios, it was observed that the grassland continued to decrease by 0.86 % to 7.34 %, and the forest and built-up land continued to increase, of which forest increased by 2.34 % to 4.03 %, and built-up land increased by 21.02 % to 61.08 %. Cropland only increased in SSP585 scenario, by 4.76 %, but declining by 2.93 % in SSP126 and SSP245 scenario. (3) In future scenarios, the expansion of built-up land has escalated the risk of cropland and grassland loss. Based on the distribution of key land use conversions, four categories of prioritized land management regions and corresponding measures have been proposed. This provided a potential pathway to mitigate risks associated with the protection of cropland and ecological land. Therefore, this study was instrumental in understanding the mechanisms of land use changes in coal resource-based cities, and provided a reference for land use planning.
RESUMEN
Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2-/- mice after 6 h of intraperitoneal injection. A cell model simulating SA-ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA-sepsis patients, negatively correlated with the severity of ALI. In SA-ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation-induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA-ALI. The p-Nrf2/total-Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA-treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual-luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA-ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.
RESUMEN
Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.
Asunto(s)
Microbioma Gastrointestinal , Síndrome de Peutz-Jeghers , Humanos , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/patología , Mutación de Línea Germinal , Ácidos Grasos Volátiles , ButiratosRESUMEN
DNA binding inhibitory factor 3 (ID3) has been shown to have a key role in maintaining proliferation and differentiation. It has been suggested that ID3 may also affect mammalian ovarian function. However, the specific roles and mechanisms are unclear. In this study, the expression level of ID3 in cumulus cells (CCs) was inhibited by siRNA, and the downstream regulatory network of ID3 was uncovered by high-throughput sequencing. The effects of ID3 inhibition on mitochondrial function, progesterone synthesis, and oocyte maturation were further explored. The GO and KEGG analysis results showed that after ID3 inhibition, differentially expressed genes, including StAR, CYP11A1, and HSD3B1, were involved in cholesterol-related processes and progesterone-mediated oocyte maturation. Apoptosis in CC was increased, while the phosphorylation level of ERK1/2 was inhibited. During this process, mitochondrial dynamics and function were disrupted. In addition, the first polar body extrusion rate, ATP production and antioxidation capacity were reduced, which suggested that ID3 inhibition led to poor oocyte maturation and quality. The results will provide a new basis for understanding the biological roles of ID3 as well as cumulus cells.
Asunto(s)
Células del Cúmulo , Oocitos , Oogénesis , Progesterona , Animales , Bovinos , Femenino , Células del Cúmulo/metabolismo , Mamíferos , Mitocondrias , Oocitos/fisiología , Oogénesis/genética , Progesterona/farmacología , Progesterona/metabolismo , Proteínas Inhibidoras de la Diferenciación/metabolismoRESUMEN
Introduction: The human brain processes shape and texture information separately through different neurons in the visual system. In intelligent computer-aided imaging diagnosis, pre-trained feature extractors are commonly used in various medical image recognition methods, common pre-training datasets such as ImageNet tend to improve the texture representation of the model but make it ignore many shape features. Weak shape feature representation is disadvantageous for some tasks that focus on shape features in medical image analysis. Methods: Inspired by the function of neurons in the human brain, in this paper, we proposed a shape-and-texture-biased two-stream network to enhance the shape feature representation in knowledge-guided medical image analysis. First, the two-stream network shape-biased stream and a texture-biased stream are constructed through classification and segmentation multi-task joint learning. Second, we propose pyramid-grouped convolution to enhance the texture feature representation and introduce deformable convolution to enhance the shape feature extraction. Third, we used a channel-attention-based feature selection module in shape and texture feature fusion to focus on the key features and eliminate information redundancy caused by feature fusion. Finally, aiming at the problem of model optimization difficulty caused by the imbalance in the number of benign and malignant samples in medical images, an asymmetric loss function was introduced to improve the robustness of the model. Results and conclusion: We applied our method to the melanoma recognition task on ISIC-2019 and XJTU-MM datasets, which focus on both the texture and shape of the lesions. The experimental results on dermoscopic image recognition and pathological image recognition datasets show the proposed method outperforms the compared algorithms and prove the effectiveness of our method.
RESUMEN
The malfunction of vascular smooth muscle cells (VSMCs) is an initiating factor in the pathogenesis of pathological vascular remodeling, including hypertension-related vascular lesions. MicroRNAs (miRNAs) have been implicated in the pathogenesis of VSMC proliferation and migration in numerous cases of cardiovascular remodeling. The evidence for the regulatory role of miR-155-5p in the development of the cardiovascular system has been emerging. However, it was previously unclear whether miR-155-5p participated in the migration of VSMCs under hypertensive conditions. Thus, we aimed to define the exact role and action of miR-155-5p in VSMC migration by hypertension. Here, we detected that the level of miR-155-5p was lower in primary VSMCs from spontaneously hypertensive rats (SHRs). Its overexpression attenuated, while its depletion accelerated, the migration and oxidative damage of VSMCs from SHRs. Our dual-luciferase reporter assay showed that miRNA-155-5p directly targeted the 3'-untranslated region (3'-UTR) of BTB and CNC homology 1 (BACH1). The miR-155-5p mimic inhibited BACH1 upregulation in SHR VSMCs. By contrast, the deletion of miR-155-5p further elevated the upregulation of BACH1 in SHR-derived VSMCs. Importantly, the overexpression of miR-155-5p and knockdown of BACH1 had synergistic effects on the inhibition of VSMCs in hypertension. Collectively, miR-155-5p attenuates VSMC migration and ameliorates vascular remodeling in SHRs, via suppressing BACH1 expression.
RESUMEN
Selenium (Se) amendment could reduce mercury (Hg) bioaccumulation in crops, but sometimes it could cause excessive Se accumulation in crops and potential Se exposure risks for humans. In this study, we designed and synthesized selenium and sulfur-modified montmorillonite materials (Se/S-Mont) to effectively reduce mercury levels and avoid excessive Se enrichment in plants. The results of pot experiments (1 g Se/S-Mont/100 g soil) and field microplot trials (0.3 g Se/S-Mont/100 g soil, 8 t/ha) showed that Se/S-Mont amendments significantly reduced the Hg concentrations in water spinach and hybrid Pennisetum by 28-68% and 57%-92% (P < 0.05), respectively, while they did not lead to excessive Se bioaccumulation in the plants. Se/S-Mont was more efficient in mitigating soil Hg pollution than adding raw materials (e.g., NaSeO3) and their combinations, and they significantly reduced the available Se fraction in the soil and the Se levels in the plants (P < 0.05). The potential mechanisms revealed by X-ray absorption near-edge spectra (XANES) and pot experiments were the adsorption and slow release of Hg, S, and Se by Se/S-Mont, the high affinity between Hg and Se, competition between Se and S, and the formation of stable complexes containing Se-S-Hg. The Se/S-Mont immobilizer was easy to prepare and required the application of small amounts, and the remediation effect was relatively stable and exhibited few negative effects; therefore, the approach showed high environmental and economic potentials.
Asunto(s)
Mercurio , Selenio , Humanos , Mercurio/análisis , Bentonita , Granjas , Suelo , AzufreRESUMEN
Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.
Asunto(s)
Colestasis Intrahepática , Microbioma Gastrointestinal , Complicaciones del Embarazo , Femenino , Embarazo , Humanos , Animales , Ratones , Complicaciones del Embarazo/metabolismo , Ácidos y Sales BiliaresRESUMEN
(1) Background: DNA double strand breaks (DSBs) are the most serious form of DNA damage that affects oocyte maturation and the physiological state of follicles and ovaries. Non-coding RNAs (ncRNAs) play a crucial role in DNA damage and repair. This study aims to analyze and establish the network of ncRNAs when DSB occurs and provide new ideas for next research on the mechanism of cumulus DSB. (2) Methods: Bovine cumulus cells (CCs) were treated with bleomycin (BLM) to construct a DSB model. We detected the changes of the cell cycle, cell viability, and apoptosis to determine the effect of DSBs on cell biology, and further evaluated the relationship between the transcriptome and competitive endogenous RNA (ceRNA) network and DSBs. (3) Results: BLM increased γH2AX positivity in CCs, disrupted the G1/S phase, and decreased cell viability. Totals of 848 mRNAs, 75 long noncoding RNAs (lncRNAs), 68 circular RNAs (circRNAs), and 71 microRNAs (miRNAs) in 78 groups of lncRNA-miRNA-mRNA regulatory networks, 275 groups of circRNA-miRNA-mRNA regulatory networks, and five groups of lncRNA/circRNA-miRNA-mRNA co-expression regulatory networks were related to DSBs. Most differentially expressed ncRNAs were annotated to cell cycle, p53, PI3K-AKT, and WNT signaling pathways. (4) Conclusions: The ceRNA network helps to understand the effects of DNA DSBs activation and remission on the biological function of CCs.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Femenino , Animales , Bovinos , Roturas del ADN de Doble Cadena , ARN Circular/genética , ARN Largo no Codificante/genética , Células del Cúmulo/metabolismo , Fosfatidilinositol 3-Quinasas/genética , MicroARNs/genética , ARN Mensajero/genética , ADNRESUMEN
There is a strong association between soyfoods or soybean product consumption and adolescent health, but there are few studies on the association between soyfoods or soybean product consumption and psychological symptoms among university students. To this end, this study investigated the association between soyfoods or soybean products consumption and psychological symptoms among Chinese university students and analyzed the association between them. A three-stage stratified whole-group sampling method was used to administer questionnaires on soyfoods or soybean products consumption and psychological symptoms to 7742 university students in China. Self-assessment questionnaires were also administered to confounding variables such as basic demographic information, family status, parental education, body mass index (BMI), and moderate and vigorous physical activity (MVPA). The chi-square test, one-way ANOVA, and logistic regression analysis were used to explore the association and differences between soyfoods or soybean products consumption and psychological symptoms. The proportion of Chinese university students' soyfoods or soybean products consumption in ≤one time/week, two-four times/week, and ≥five times/week were 38.81%, 40.24%, and 20.95%, respectively. University students' psychological symptoms problem detection rate was 16.22%. The detection rate of psychological symptoms was lower among university male students (14.75%) than female students (17.35%), and the difference was statistically significant (χ2 = 9.525, p < 0.01). After adjusting for relevant covariates, students with soyfoods or soybean products consumption ≤one time/week (OR = 1.83, 95% CI:1.52, 2.21) had a higher risk of psychological symptoms compared to university students with soyfoods or soybean products consumption ≥five time/week (p < 0.01). During the COVID-19 pandemic, Chinese university students had lower consumption of soyfoods or soybean products and a higher detection rate of psychological symptoms. There was a negative association between soyfoods or soybean products consumption and psychological symptoms. Our study provides a scientific reference for the government and educational decision-making authorities and suggests that education on eating behavior and dietary guidance should be emphasized among university students in the future to maintain a reasonable consumption of soyfoods or soybean products for better physical and mental health development.
Asunto(s)
COVID-19 , Glycine max , Adolescente , Humanos , Masculino , Femenino , Estudios Transversales , Universidades , Pandemias , COVID-19/epidemiología , COVID-19/psicología , Estudiantes/psicologíaRESUMEN
BACKGROUND: T-box transcription factor 2 (TBX2) is a member of T-box gene family whose members are highly conserved in evolution and encoding genes and are involved in the regulation of developmental processes. The encoding genes play an important role in growth and development. Although TBX2 has been widely studied in cancer cell growth and development, its biological functions in bovine cumulus cells remain unclear. OBJECTIVES: This study aimed to investigate the regulatory effects of TBX2 in bovine cumulus cells. METHODS: TBX2 gene was knockdown with siRNA to clarify the function in cellular physiological processes. Cell proliferation and cycle changes were determined by xCELLigence cell function analyzer and flow cytometry. Mitochondrial membrane potential and autophagy were detected by fluorescent dye staining and immunofluorescence techniques. Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression changes of proliferation and autophagy-related proteins. Aadenosine triphosphate (ATP) production, glucose metabolism, and cholesterol synthesis of cumulus cells were measured by optical density and chemiluminescence analysis. RESULTS: After inhibition of TBX2, the cell cycle was disrupted. The levels of apoptosis, ratio of light chain 3 beta II/I, and reactive oxygen species were increased. The proliferation, expansion ability, ATP production, and the amount of cholesterol secreted by cumulus cells were significantly decreased. CONCLUSIONS: TBX2 plays important roles in regulating the cells' proliferation, expansion, apoptosis, and autophagy; maintaining the mitochondrial function and cholesterol generation of bovine cumulus cells.
Asunto(s)
Autofagia , Células del Cúmulo , Femenino , Animales , Bovinos , Células del Cúmulo/metabolismo , Proliferación Celular , Apoptosis/genética , Mitocondrias , Colesterol/metabolismo , Colesterol/farmacología , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacologíaRESUMEN
Increasing evidence indicates that gut microbiota may play a key role in vaccination immunity. Here, we investigate whether the human gut microbiota and metabolic function correlate with the BBIBP-CorV vaccine response. A total of 207 participants who received the BBIBP-CorV vaccine are enrolled. The gut microbiome and metabolic functions are investigated using metagenomic sequencing and metabolomic assays. We find that BBIBP-CorV vaccination is accompanied by altered microbiome composition and functional pathways, and the gut microbiome and its functional profiles correlate with the vaccine response. The levels of short-chain fatty acids (SCFAs) are much higher in the high antibody response group compared to the low response group, and several SCFAs display a positive correlation with the antibody response. Our study highlights that the gut microbiome and its function is associated with the BBIBP-CorV vaccine response, providing evidence for further exploration of microbiome modulation to improve COVID-19 vaccine efficacy.