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Lacking effective therapeutic targets heavily restricts the improvement of clinical prognosis for patients diagnosed with esophageal squamous cell carcinoma (ESCC). Ubiquitin Specific Peptidase 21 (USP21) is dysregulated in plenty of human cancers, however, its potential function and relevant molecular mechanisms in ESCC malignant progression as well as its value in clinical translation remain largely unknown. Here, in vitro and in vivo experiments revealed that aberrant upregulation of USP21 accelerated the proliferation and metastasis of ESCC in a deubiquitinase-dependent manner. Mechanistically, we found that USP21 binds to, deubiquitinates, and stabilizes the G3BP Stress Granule Assembly Factor 1 (G3BP1) protein, which is required for USP21-mediated ESCC progression. Further molecular studies demonstrated that the USP21/G3BP1 axis played a tumor-promoting role in ESCC progression by activating the Wnt/ß-Catenin signaling pathway. Additionally, disulfiram (DSF), an inhibitor against USP21 deubiquitylation activity, markedly abolished the USP21-mediated stability of G3BP1 protein and significantly displayed an anti-tumor effect on USP21-driving ESCC progression. Finally, the regulatory axis of USP21/G3BP1 was demonstrated to be aberrantly activated in ESCC tumor tissues and closely associated with advanced clinical stages and unfavorable prognoses, which provides a promising therapeutic strategy targeting USP21/G3BP1 axis for ESCC patients.
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Purpose: During the period of COVID-19 pandemic, the social restrictions and isolation exerted a significant impact on the sleep quality of Chinese college students. This study aims to delve into the influence of physical activity on the sleep quality of college students as well as the mediating roles of stress and smartphone addiction. Materials and Methods: A cohort of 274 eligible college students (146 males and 128 females) were selected for the investigation. The International Physical Activity Questionnaire Short Form, Stress Perception Scale, Smartphone Addiction Scale, and Pittsburgh Sleep Quality Index were employed to assess the levels of physical activity, stress, smartphone addiction, and sleep quality among college students. For data analysis, descriptive statistics, correlation analysis, and chained mediation effect tests were performed sequentially. Results: The findings revealed: (1) a significant negative correlation between physical activity and stress, smartphone addiction, and sleep quality among college students (r = -0.216, p < 0.001; r = -0.224, p < 0.001; r = -0.259, p < 0.001); (2) independent mediating roles of stress and smartphone addiction in the relationship between physical activity and sleep quality; and (3) chained mediating effects of stress and smartphone addiction in the association between physical activity and sleep quality. Conclusion: This study deepens our comprehension of how physical activity augments the quality of slumber, concurrently emphasizing that mitigating stress levels and alleviating smartphone addiction constitute effective strategies for preventing sleep issues among college students.
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OBJECTIVE: Cardiac ischemia-reperfusion (I/R) injury has negative effects on the brain and can even lead to the occurrence of ischemic stroke. Clinical evidence shows that Danhong injection (DHI) protects the heart and brain following ischemic events. This study investigated the mechanisms and key active compounds underlying the therapeutic effect of DHI against brain damage induced by cardiac I/R injury. METHODS: The gene expression omnibus database provided GSE66360 and GSE22255 data sets. The R programming language was used to identify the common differentially expressed genes (cDEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed, and protein-protein interaction network was constructed. Active compounds of DHI were collected from the Traditional Chinese Medicine Systems Pharmacology database. Molecular docking and molecular dynamics simulations were performed. The MMPBSA method was used to calculate the binding-free energy. The pkCSM server and DruLiTo software were used for Absorption, Distribution, metabolism, excretion, and toxicity (ADMET) analysis and drug-likeness analysis. Finally, in vitro experiments were conducted to validate the results. RESULTS: A total of 27 cDEGs had been identified. The PPI and enrichment results indicated that TNF-α was considered to be the core target. A total of 80 active compounds were retrieved. The molecular docking results indicated that tanshinone I (TSI), tanshinone IIA (TSIIA), and hydroxyl safflower yellow A (HSYA) were selected as core active compounds. Molecular dynamics verification revealed that the conformations were relatively stable without significant fluctuations. MMPBSA analysis revealed that the binding energies of TSI, TSIIA, and HSYA with TNF-α were -36.01, -21.71, and -14.80 kcal/mol, respectively. LEU57 residue of TNF-α has the highest contribution. TSI and TSIIA passed both the ADMET analysis and drug-likeness screening, whereas HSYA did not. Experimental verification confirmed that DHI and TSIIA reduced the expression of TNF-α, NLRP3, and IL-1ß in the injured H9C2 and rat brain microvascular endothelial cells. CONCLUSION: TNF-α can be considered to be a key target for BD-CI/R. TSIIA in DHI exerts a significant inhibitory effect on the inflammatory damage of BD-CI/R, providing new insights for future drug development.
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Background: Internet addiction poses a significant threat to the health of college students worldwide, but physical activity, as a highly safe and effective rehabilitative measure, has shown promise for alleviating this issue nowadays. However, during the COVID-19 pandemic, the mediating processes in this association remained unclear. This study aims to explore the impact of physical activity on internet addiction among college students and the mediating role of subjective well-being. Methods: A survey was conducted on 216 eligible college students using the physical activity level scale, the internet addiction test, and the subjective well-being scale. For data analysis, independent sample t-tests, correlation analysis, hierarchical regression analysis, and mediating effect tests were in turn carried out in this work. Results: The study revealed noteworthy gender disparities in physical activity and internet addiction among college students (ß = -0.356, p < 0.01; ß = 0.140, p < 0.05). Compared to females, male students manifest elevated levels of physical activity and lower scores in internet addiction. Physical activity and subjective well-being exerted a significantly negative predictive influence on internet addiction (ß = -0.162, p < 0.05; ß = -0.508, p < 0.001). What's more, subjective well-being assumed a crucial mediating role in the relationship between physical activity and internet addiction, with the mediating effect accounting for 72.81% of the total effect. Conclusion: This study deepens the understanding of how physical activity reduces internet addiction risk while emphasizing that enhancing subjective well-being is an effective strategy for college students to cope with Internet addiction.
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COVID-19 , Exercice physique , Dépendance à Internet , Étudiants , Humains , Mâle , Femelle , COVID-19/épidémiologie , COVID-19/psychologie , Exercice physique/psychologie , Étudiants/psychologie , Étudiants/statistiques et données numériques , Études transversales , Chine/épidémiologie , Dépendance à Internet/épidémiologie , Dépendance à Internet/psychologie , Jeune adulte , Universités , Enquêtes et questionnaires , Adulte , Facteurs sexuels , Adolescent , Comportement toxicomaniaque/psychologieRÉSUMÉ
BACKGROUND: Solamargine (SM) has been shown to play anti-tumor role in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of SM in HCC progression deserve further exploration. METHODS: HCC cell proliferation and apoptosis were assessed by cell counting kit 8 assay, colony formation assay and flow cytometry. Ferroptosis was evaluated by detecting the levels of Fe2+, iron, MDA, ROS and GSH in HCC cells. In addition, mitochondrial carrier 1 (MTCH1) mRNA level was detected by quantitative real-time PCR. Western blot was used to test MTCH1 and signal transduction and activation of transcription 1 (STAT1) protein levels. Dual-luciferase reporter assay was employed to analyze the interaction between STAT1 and MTCH1. A mouse xenograft model was also constructed to explore the role of SM in vivo. RESULTS: SM could potentially suppress HCC cell growth by inducing ferroptosis. MTCH1 was highly expressed in HCC tissues and cells, and its silencing inhibited HCC cell proliferation, promoted apoptosis and ferroptosis. MTCH1 expression was reduced by SM, and its overexpression reversed SM-induced HCC cell apoptosis and ferroptosis. Furthermore, STAT1 facilitated MTCH1 transcription and promoted its expression. Besides, STAT1 expression could be reduced by SM, and its overexpression abolished the decreasing effect of SM on MTCH1 expression. In vivo, SM suppressed HCC tumor growth by reducing MTCH1 expression. CONCLUSION: SM promoted HCC cell apoptosis and ferroptosis via the STAT1/MTCH1 axis.
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Background: Nowadays, it is widely acknowledged that mobile phone addiction is a risky factor for insomnia symptoms, but to date, people know little about the underlying relationship between them among undergraduates during the COVID-19 pandemic. The purpose of the present study was to examine the potential association between mobile phone addiction and insomnia, as well as the mediating role of social anxiety and the moderating role of physical activity. Methods: Using the Mobile Phone Addiction Tendency Scale, Social Phobia Inventory, Physical Activity Rating Scale and Insomnia Severity Index, 301 eligible college students in China were investigated. For data analysis, descriptive analysis, correlation analysis, moderating effect test, moderating effect test were carried out in turn. Results: The findings revealed a favorable correlation between mobile phone addiction, social anxiety and insomnia, as well as between social anxiety and insomnia. But physical activity was negatively correlated with social anxiety and mobile phone addiction, and social anxiety partially mediated the relationship between mobile phone addiction and insomnia. Additionally, physical activity played a significant moderating effect between mobile phone addiction and social anxiety. Conclusion: This study advances the knowledge of how mobile phone addiction raises the likelihood of experiencing insomnia symptoms, and also implies that upping physical activity level could lessen the harmful impacts from mobile phone addiction.
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COVID-19 , Troubles de l'endormissement et du maintien du sommeil , Humains , COVID-19/épidémiologie , Pandémies , Troubles de l'endormissement et du maintien du sommeil/épidémiologie , Chine/épidémiologie , Facteurs de risque , Étudiants , Addiction à la technologieRÉSUMÉ
Objective@#To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients.@*Methods@#From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed.@*Results@#A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05).@*Conclusion@#The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.
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It is desired that a fixed beamformer should maintain the frequency-invariant beampattern and achieve the high white noise gain (WNG), i.e., high robustness against the mismatch in practice. However, existing methods for the design of concentric circular differential microphone arrays (CCDMAs) cannot achieve a compromise between the high robustness and the frequency-invariant beampattern. To address this problem, a new analytical expression for the synthesized beampattern of CCDMAs is derived without any truncation error. Then CCDMAs are designed by matching mode coefficients of the approximated synthesized beampattern to that of the target differential beampattern, where an adjustable truncation order is utilized to enable a trade-off between the robustness and the beampattern distortion. A simple and effective procedure is presented to determine the frequency-wise truncation order. The proposed method reduces to three existing methods, i.e., the Jacobi-Anger method, the improved Jacobi-Anger method, and the minimum mean square error-based method, for a fixed truncation order, which in turn establishes a close connection with these methods and provides a unified view on the design of the CCDMAs. The superiority of the proposed method in terms of robustness and beampattern distortion is demonstrated through computer simulations.
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Ischemic acute kidney injury (AKI) is a prevalent disorder among hospitalized patients worldwide. Astragaloside IV (AS-IV) has been shown to protect against ischemic AKI. However, the specific effects and mechanisms of AS-IV on alleviating kidney ischemia-reperfusion (I/R) injury remain unclear. The objective of this research was to elucidate the regulatory targets and mechanisms through which AS-IV protects kidney I/R injury. A combination of network pharmacology, molecular docking, molecular dynamics (MD) simulation, pharmacodynamic study and Western blot were employed to explore the underlying mechanisms. Network pharmacology revealed that ferroptosis was a potential mechanism of AS-IV against kidney I/R injury. Molecular docking and MD simulations demonstrated strong binding affinity between the GPX4/SLC7A11 and AS-IV. The experimental verification demonstrated that AS-IV improved cell proliferation, decreased the level of ROS and Fe2+, and increased the expressions of GPX4 and SLC7A11 as same as Ferrostatin-1 in OGD/R-injured HUVECs. In conclusion, AS-IV had a significant inhibition on ferroptosis in kidney I/R injury, providing a new perspective for drug development on kidney I/R injury. Definitely, further exploration in vivo is necessary to fully understand whether AS-IV alleviates kidney I/R injury through inhibiting endothelial ferroptosis.
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ABSTRACT Purpose Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. Methods In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). Results The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. Conclusions PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.
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This paper analyzes the media frames adopted by the official WeChat and Sina Weibo accounts of the People's Daily between January 1 and December 31, 2020, for reports about female medical personnel involved in pandemic prevention and control. Although the number of female medical personnel involved in pandemic prevention and control far exceeded that of their male counterparts, the extent of media reports on the former was far less than that of the latter. The human interest frame about female medical personnel was mainly applied, while the use of the action frame was less frequent, which highlighted the gender identity and family role of these women but weakened their professional identity. This was not conducive to praising the contributions of female medical personnel in fighting the pandemic. The media frames of reporting medical personnel in WeChat and Sina Weibo accounts of the People's Daily are not always the same. After Wuhan's lockdown ended on April 8, the proportion of the human interest frame of the report text of female medical personnel decreased, and the proportion of the action frame increased, while the proportion of the human interest frame of the report text of male medical personnel increased and the proportion of the action frame decreased. Previous studies mainly analyzed the use of the media frames of female news personalities, but few studies focused on whether women had the possibility of breaking away from the gender media frames. This study shows that some female medical personnel with exceptional professional competence are likely to transcend the gender media frames and receive similar coverage to that of male medical professionals, like Li Lanjuan and Chen Wei.
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PURPOSE: Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. METHODS: In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). RESULTS: The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. CONCLUSIONS: PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.
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Tumeurs de la prostate , Mâle , Humains , Tumeurs de la prostate/imagerie diagnostique , Tumeurs de la prostate/anatomopathologie , Imagerie par résonance magnétique , Antigène spécifique de la prostate , Biopsie guidée par l'image , Prostate/imagerie diagnostique , Prostate/anatomopathologie , Études rétrospectivesRÉSUMÉ
PURPOSE: This study aimed to investigate whether N6-methyladenosine (m6A)-related long non-coding RNAs (m6ARelncRNAs) could provide novel tools to predict overall survival of renal clear cell carcinoma. METHODS: The transcriptomic data and clinical information of patients with renal clear cell carcinoma from The Cancer Genome Atlas (TCGA) were analysed. Distinct m6A modification patterns were systemically analysed via consensus clustering analysis. An m6ARelncRNA signature was constructed in the training cohort using the least absolute shrinkage and selection operator (LASSO) analysis and validated in the test cohort. Potential predictive accuracy of the signature was further assessed via Kaplan-Meier survival, univariate and multivariate Cox regression and subgroup analyses. The Tumour Immune Dysfunction and Exclusion (TIDE) algorithm was used to investigate the role of m6ARelncRNAs in guiding immunotherapy for patients with renal carcinoma. RESULTS: An m6ARelncRNA signature based on only six lncRNAs was successfully constructed. The high-risk group derived from this signature had significantly poorer overall survival in both training and test cohorts (p < 0.001). Independent prognostic analysis further revealed that m6ARelncRNA risk (p < 0.01) was an independent risk factor for survival outcomes of renal carcinoma. TIDE algorithm revealed that immunotherapy response was poorer in the high-risk group than in the low-risk group. Drug sensitivity analysis based on IC50 revealed that high-risk patients were potentially sensitive to various anti-tumour drugs, including bortezomib, cisplatin, docetaxel, etoposide and sunitinib. CONCLUSION: m6ARelncRNAs provide novel tools that can be used to predict overall survival and examine the immune microenvironment of renal clear cell carcinoma.
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Néphrocarcinome , Tumeurs du rein , ARN long non codant , Humains , Néphrocarcinome/génétique , ARN long non codant/génétique , Sunitinib , Adénosine , Tumeurs du rein/génétique , Microenvironnement tumoral/génétiqueRÉSUMÉ
Objective: Smartphone addiction, as a key topic in the current field of behavioral addictions and public health, has brought many negative impacts on the physical, psychological, interpersonal communication, and even academic performance among contemporary college students. Therefore, the purpose of this study is to offer ideas for solving smartphone addiction among college students through investigating the potential mediating effect of self-esteem in the relationship between physical activity and smartphone addiction. Methods: By the quota sampling, a cross-sectional study was conducted to investigate 650 college students from 10 colleges in Guangzhou Higher Mega Center, and several self-reported instruments including physical activity rating scale-3 (PARS-3), mobile phone addiction tendency scale (MPATS), self-esteem scale (SES) were used to collect the related data needed for the present study. The descriptive analysis, correlation analysis, hierarchical regression analysis, and mediating effect analysis in this study were performed in turn. Results: The results showed that physical activity (r = -0.124, p < 0.01) and self-esteem (r = -0.360, p < 0.01) were all negatively correlated with smartphone addiction, and both could also significantly and negatively predict smartphone addiction. There was a positive correlation between physical activity and self-esteem (r = 0.084, p < 0.05), and self-esteem could be significantly predicted by physical activity. And more important, the relationship between physical activity and smartphone addiction could be partially mediated by self-esteem, and the indirect effect value was -0.346 (95% Boot CI = -0.695; -0.023), along with the mediating effect accounted for 24% of the total effect between physical activity and smartphone addiction. Conclusion: The current study shows that physical activity could not only directly reduce smartphone addiction, but also decrease smartphone addiction by indirectly improving self-esteem, which is important in practice for solving this troublesome issue and then gradually developing a healthy behavior in daily life for college students in China, and even across the world in near future.
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The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) is critical for bone formation and regeneration. A high non-/delayed-union rate of fracture healing still occurs in specific populations, implying an urgent need to discover novel targets for promoting osteogenesis and bone regeneration. Long non-coding (lnc)RNAs are emerging regulators of multiple physiological processes, including osteogenesis. Based on differential expression analysis of RNA sequencing data, we found that lncRNA AC132217.4, a 3'UTR-overlapping lncRNA of insulin growth factor 2 (IGF2), was highly induced during osteogenic differentiation of BMSCs. Afterward, both gain-of-function and loss-of-function experiments proved that AC132217.4 promotes osteoblast development from BMSCs. As for its molecular mechanism, we found that AC132217.4 binds with IGF2 mRNA to regulate its expression and downstream AKT activation to control osteoblast maturation and function. Furthermore, we identified two splicing factors, splicing component 35 KDa (SC35) and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), which regulate the biogenesis of AC132217.4 at the post-transcriptional level. We also identified a transcription factor, ALX1, which regulates AC132217.7 expression at the transcriptional level to promote osteogenesis. Importantly, in-vivo over-expression of AC132217.4 essentially promotes the bone healing process in a murine tibial drill-hole model. Our study demonstrates that lncRNA AC132217.4 is a novel anabolic regulator of BMSC osteogenesis and could be a plausible therapeutic target for improving bone regeneration.
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Protéines à homéodomaine , Cellules souches mésenchymateuses , Ostéogenèse , ARN long non codant , Animaux , Différenciation cellulaire/génétique , Protéines à homéodomaine/génétique , Facteur de croissance IGF-II/génétique , Facteur de croissance IGF-II/métabolisme , Souris , Ostéogenèse/génétique , Protéines proto-oncogènes c-akt/génétique , Protéines proto-oncogènes c-akt/métabolisme , ARN long non codant/génétique , ARN long non codant/métabolisme , Transduction du signalRÉSUMÉ
Ankylosing spondylitis (AS) is an autoimmune disease with unknown aetiology. To unravel the mechanisms mediating AS pathogenesis, we profiled peripheral blood mononuclear cells (PBMCs) from AS patients and healthy subjects using 10X single-cell RNA sequencing. The frequencies of immune cell subsets were evaluated by flow cytometry. NK cells were purified from PBMCs using isolation kit and were examined for gene expression by RT-qPCR. Plasma levels of cytolytic molecules were examined by enzyme-linked immunosorbent assay. Compared to healthy controls, AS patients showed a significant decrease in total NK cells as well as CD56dim NK subset, whereas CD56bright NK cells were increased. Additionally, impaired expression of cytotoxic genes in NK cells of AS patients was observed by bioinformatics algorithm and verified by RT-qPCR and flow cytometry. Consistent with changes in transcriptomics, we found decreased plasma levels of granzymes, but not granulysin, in AS patients. Furthermore, Pearson correlation analysis revealed a negative correlation between plasma GZMB levels and disease activity (r = -0.5275, p = 0.0358). No correlation was observed between plasma cytolytic molecules and biochemical indexes (ESR and CRP). Our findings uncover altered NK cell subsets and cytotoxic profiles in peripheral circulation of AS patients at single-cell resolution.
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Pelvispondylite rhumatismale , Antigènes CD56/génétique , Cytométrie en flux , Humains , Cellules tueuses naturelles , Agranulocytes/métabolisme , RNA-Seq , Pelvispondylite rhumatismale/métabolismeRÉSUMÉ
The Notch signaling pathway plays an important role in otic neurogenesis by regulating the differentiation of inner ear hair cells and supporting cells. Notch-regulated differentiation is required for the regeneration of hair cells in the inner ear. The temporal expression pattern of Notch ligands and receptors during in vitro hair cell-like cell differentiation from human embryonic stem cells (hESCs) was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Subsequently, pAJ-U6-shRNA-CMV-Puro/GFP recombinant lentiviral vectors encoding short hairpin RNAs were used to silence JAG-1, JAG-2, and DLL-1, according to the temporal expression pattern of Notch ligands. Then, the effect of each ligand on the in vitro differentiation of hair cells was examined by RT-PCR, immunofluorescence, and scanning electron microscopy (SEM). The results showed that the individual deletion of JAG-2 or DLL-1 had no significant effect on the differentiation of hair cell-like cells. However, the simultaneous inhibition of both DLL-1 and JAG-2 increased the number of hair cell-like cells and decreased the number of supporting cells. JAG-2 and DLL-1 may have a synergistic role in in vitro hair cell differentiation.
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Bladder cancer (BLCA) has a high incidence and recurrence rate, and the effect of immunotherapy varies from person to person. Immune-related genes (IRGs) have been shown to be associated with immunotherapy and prognosis in many other cancers, but their role in immunogenic BLCA is less well defined. In this study, we constructed an eight-IRG risk model, which demonstrated strong prognostic and immunotherapeutic predictive power. The signature was significantly related to tumor clinicopathological characteristics, tumor class, immune cell infiltration and mutation status. Additionally, a nomogram containing the risk score and other potential risk factors could effectively predict the long-term overall survival probability of BLCA patients. The enriched mechanisms identified by gene set enrichment analysis suggested that the reason why this signature can accurately distinguish high- and low-risk populations may be closely related to the different degrees of innate immune response and T cell activation in different patients.
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Tumeurs de la vessie urinaire , Marqueurs biologiques tumoraux/génétique , Régulation de l'expression des gènes tumoraux , Humains , Nomogrammes , Pronostic , Tumeurs de la vessie urinaire/anatomopathologieRÉSUMÉ
Microgravity impacts various aspects of human health. Yet the mechanisms of spaceflight-induced health problems are not elucidated. Here, we mapped the fusion systemic analysis of the serum metabolome and the circulating microRNAome in a hindlimb unloading rat model to simulate microgravity. The response of serum metabolites and microRNAs to simulated microgravity was striking. Integrated pathway analysis of altered serum metabolites and target genes of the significantly altered circulating miRNAs with Integrated Molecular Pathway-Level Analysis (IMPaLA) software was mainly suggestive of modulation of neurofunctional signaling pathways. Particularly, we revealed significantly increased miR-383-5p and decreased aquaporin 4 (AQP4) in the hippocampus. Using rabies virus glycoprotein-modified exosomes, delivery of miR-383-5p inhibited the expression of AQP4 not only in rat C6 glioma cells in vitro but also in the hippocampus in vivo. Using bioinformatics to map the crosstalk between the circulating metabolome and miRNAome could offer opportunities to understand complex biological systems under microgravity. Our present results suggested that the change of miR-383-5p level and its regulation of target gene AQP4 was one of the potential molecular mechanisms of microgravity-induced cognitive impairment in the hippocampus.
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TRPM7 is a member of the transient receptor potential cation channel (TRP channel) subfamily M and possesses both an ion channel domain and a functional serine/threonine α-kinase domain. It has been proven to play an essential role in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). However, the signaling pathway and molecular mechanism for TRPM7 in regulating osteogenic differentiation remain largely unknown. In this study, the potential role and mechanism of TRPM7 in the osteogenic differentiation of hBMSCs were investigated. The results showed that the expression of TRPM7 mRNA and protein increased, as did the osteogenic induction time. Upregulation or inhibition of TRPM7 could promote or inhibit the osteogenic differentiation of hBMSCs for 14 days. It was also found that the upregulation or inhibition of TRPM7 promoted or inhibited the activity of PLC and SMAD1, respectively, during osteogenic differentiation. PLC could promote osteogenic differentiation by upregulating the activity of SMAD1. However, inhibition of PLC alone could reduce the activity of SMAD1 but not inhibit completely the activation of SMAD1. Therefore, we inferred that it is an important signaling pathway for TRPM7 to upregulate the activity of SMAD1 through PLC and thereby promote the osteogenic differentiation of hBMSCs, but it is not a singular pathway. TRPM7 may also regulate the activation of SMAD1 through other ways, except for PLC, during osteogenic differentiation of hBMSCs.