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BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Nomogramas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Subpopulações de Linfócitos/imunologia , Adulto , Contagem de LinfócitosRESUMO
BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.
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Actinas , Meiose , Oócitos , Proteína cdc42 de Ligação ao GTP , Animais , Oócitos/metabolismo , Camundongos , Feminino , Actinas/metabolismo , Actinas/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteína cdc42 de Ligação ao GTP/genética , Fosforilação , Fuso Acromático/metabolismoRESUMO
OBJECTIVE: This study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters. METHODS: A retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH. RESULTS: PTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH. CONCLUSIONS: CBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.
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Pneumopatias , Pneumotórax , Humanos , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Pneumotórax/patologia , Incidência , Estudos Retrospectivos , Relevância Clínica , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias/diagnóstico por imagem , Pneumopatias/epidemiologia , Pneumopatias/complicações , Tomografia Computadorizada de Feixe Cônico , Hemorragia/epidemiologia , Hemorragia/etiologia , Biópsia por Agulha/efeitos adversos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Fatores de RiscoRESUMO
BACKGROUND: The aims of the present study were to investigate the incidence of nurses who suffered anxiety during the COVID-19 pandemic and to explore how expressive suppression influences the relationship between family function and anxiety. METHODS: This study used cross-sectional research and simple random sampling. A total of 300 questionnaires were distributed and 254 questionnaires were qualified after invalid questionnaires were proposed, thus a total of 254 female nurses from a tertiary hospital were included in this study. The measurement included General demographic questionnaires, the Self-Scale Anxiety, Scale (SAS), Emotion Regulation Strategies Questionnaire (ERQ), and Family Function Assessment (FAD). T-test, nonparametric Wilcoxon or Kruskal-Wallis test, χ2 test, Pearson or Spearman correlation analysis, multiple stepwise regression and bootstrap methods was performed to analyze the data. RESULTS: In this study, 22.4% of the nurses exhibited anxiety symptoms, with 17.7% eliciting mild anxiety symptoms, 4.3% showing moderate anxiety symptoms and 0.4% with severe anxiety symptoms. Family function and expressive suppression were positively associated with anxiety severity. And family function influenced anxiety among nurses via direct and indirect (Expressive suppression -mediated) pathways. CONCLUSIONS: Expressive suppression partially mediated the influence of family function on anxiety symptom. To this end, nurse administrators should establish a robust mental health support system encompassing psychological counseling and emotional support groups. Furthermore, nurse administrators should consistently inquire about nurses' family situations, encourage nurses to articulate their emotions and needs candidly, both within the domestic sphere and the workplace, while refraining from excessive self-repression.
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BACKGROUND: Burnout is very important to nurses' physical and mental health and career development. Current approaches to assessing nurse burnout tend to use a total score modeling paradigm to explore the impact of external factors on burnout. The purpose of this study is to delve into the item-level relationship between nurse burnout and its influencing factors at both the social and psychological levels using a network analysis approach. METHODS: This study was conducted in June 2023 and 1,005 nurses from 4 hospitals out of 8 tertiary care hospitals in Harbin were selected to participate in this study using whole cluster sampling method. Measurements included a general demographic questionnaire, Trait coping styles questionnaire, Organizational commitment questionnaire, Work-family conflict scale, Transformational leadership questionnaire, and Maslach Burnout Inventory-General Survey. RESULTS: Our results suggest that "C1 Time-Based work interference with family" showed the strongest centrality and bridging in the overall network. This finding underscores its centrality to burnout. Other strongest bridge symptoms included "E2 Reduced personal accomplishment" and "A1 Positive coping styles" indicating their strongest connections to other clusters. CONCLUSIONS: Nurse administrators should be encouraged to pay more attention to nurses' work situations and family distress, and to help nurses in a flexible way.
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BACKGROUND: The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS: This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS: GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS: This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .
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Microbioma Gastrointestinal , Hipertensão , Feminino , Humanos , Masculino , Pressão Sanguínea , China , Estudos Transversais , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: The growth and yield of pepper (Capsicum annuum L.) is often affected by the critical salt stress. Salicylic acid (SA) can improve plants' stress tolerance by promoting growth and regulating ion absorption and transportation. METHODS AND RESULTS: To uncover the alleviated mechanism of salt stress by SA in pepper, we conducted morphological, physiological, cytological, and transcriptomic analyses under a single SA treatment and NaCl with and without SA pre-treatment for 9 days. Seedlings under NaCl treatment showed yellow shrunken leaves, this tatus were alleviated by NS treatment (NaCl with SA pre-treatment). Compared with plants under NaCl treatment, those in the NS treatment showed reduced lipid peroxidation, and significantly increased contents of chlorophyll and osmotic regulators (proline, soluble sugars). Treatment with SA balanced the Na+/K+ ratio. We conducted transcriptome sequencing and identified differentially expressed genes (DEGs) contributing to alleviation of salt stress by SA in pepper. Besides photosynthesis related genes, GO and KEGG analyses revealed that the DEGs were enriched in 'sequence-specific DNA binding', 'transcription regulator activity' and 'DNA binding transcription factor activity' by GO terms. And our results showed that TFs, such as MYB, bZIP, BBX, AP2/ERF, NAC, etc., probably make a great contribution in the alleviation of salt stress by SA. CONCLUSIONS: These results reveal that SA can improve plants' stress tolerance by balancing ion absorption, gene expression and transcriptional regulation, which provide new ideas and resources for subsequent research on the mechanism of salt tolerance in pepper.
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Capsicum , Capsicum/genética , Transcriptoma/genética , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo , Cloreto de Sódio/farmacologia , Cloreto de Sódio/metabolismo , Tolerância ao Sal/genética , DNA/metabolismo , Estresse Fisiológico/genéticaRESUMO
BACKGROUND: The relationship between the Coronavirus Disease 2019 (COVID-19) pandemic, which is a traumatic event for adolescents, and procrastination is not clear. Mental health may play an important role in this relationship; however, the underlying mechanisms remain unknown. This study aimed to construct chain mediation models to examine whether anxiety and depression symptoms mediate the effects of the COVID-19 pandemic on procrastination in adolescents. METHODS: A convenience sample of 12 middle and high schools in Harbin, China, with four follow-up online surveys was conducted during the COVID-19 pandemic. A total of 4,156 Chinese adolescents were enrolled in this study, of whom ages 11-18 (Mean = 13.55; SD = 1.18), 50.75% were male, and 93.24% were middle school students. Descriptive demographic analysis and Pearson's correlation analysis of the effects of the COVID-19 pandemic (T1), anxiety(T2), depression (T3), and procrastination (T4) were performed in SPSS 22.0. Chain mediation analysis performed with Mplus 8.3. RESULTS: The effects of the COVID-19 pandemic, anxiety symptoms, depression symptoms, and procrastination were positively correlated (P < 0.01). The effects of the COVID-19 pandemic have a direct link on adolescent procrastination (effect = 0.156; SE = 0.031; 95%CI: 0.092, 0.214), and have three indirect paths on procrastination: the independent mediating role of anxiety symptoms was 29.01% (effect = 0.047; SE = 0.012; 95%CI: 0.024, 0.072), the independent mediating role of depression symptoms was 29.01% (effect = 0.047; SE = 0.010; 95%CI: 0.030, 0.068), as well as the completely chain mediating role of anxiety and depression symptoms was 15.43% (effect = 0.025; SE = 0.005; 95%CI: 0.017, 0.036). CONCLUSIONS: Our results suggest that anxiety and depressive symptoms are part of a causal chain between the effects of the COVID-19 pandemic and procrastination among Chinese adolescents. To effectively reduce their procrastination, attention should be paid to the emotional distress caused to adolescents by major events such as the COVID-19 epidemic. All data were taken from self-reported measures and one city in China, which may bias the results and limit their generalizability.
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COVID-19 , Procrastinação , Adolescente , Masculino , Humanos , Feminino , Pandemias , Estudos Longitudinais , Depressão/epidemiologia , COVID-19/epidemiologia , Ansiedade/epidemiologia , China/epidemiologiaRESUMO
BACKGROUND AIMS: Gingival mesenchymal stem cells (GMSCs) demonstrate high proliferation, trilineage differentiation and immunomodulatory properties. Parkinson disease (PD) is the second most common type of neurodegenerative disease. This study aimed to explore the effect and mechanism of GMSC-based therapy in 6-hydroxydopamine-induced PD rats. METHODS: RNA sequencing and quantitative proteomics technology was used to validate the neuroprotective role of GMSCs therapeutic in 6-Hydroxydopamine -induced PD model in vitro and in vivo. Western blotting, immunofluorescence and real-time quantitative PCR verified the molecular mechanism of GMSCs treatment. RESULTS: Intravenous injection of GMSCs improved rotation and forelimb misalignment behavior, enhanced the anti-apoptotic B-cell lymphoma 2/B-cell lymphoma 2-associated X axis, protected tyrosine hydroxylase neurons, decreased the activation of astrocytes and reduced the astrocyte marker glial fibrillary acidic protein and microglia marker ionized calcium-binding adaptor molecule 1 in the substantia nigra and striatum of PD rats. The authors found that GMSCs upregulated nerve regeneration-related molecules and inhibited metabolic disorders and the activation of signal transducer and activator of transcription 3. GMSCs showed a strong ability to protect neurons and reduce mitochondrial membrane potential damage and reactive oxygen species accumulation. The safety of GMSC transplantation was confirmed by the lack of tumor formation following subcutaneous transplantation into nude mice for up to 8 weeks. CONCLUSIONS: The authors' research helps to explain the mechanism of GMSC-based therapeutic strategies and promote potential clinical application in Parkinson disease.
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Células-Tronco Mesenquimais , Doenças Neurodegenerativas , Doença de Parkinson , Animais , Cálcio/metabolismo , Gengiva , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Camundongos , Camundongos Nus , Neurônios/metabolismo , Oxidopamina/metabolismo , Oxidopamina/farmacologia , Oxidopamina/uso terapêutico , Doença de Parkinson/terapia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia , Fator de Transcrição STAT3/uso terapêutico , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/farmacologia , Tirosina 3-Mono-Oxigenase/uso terapêuticoRESUMO
BACKGROUND AIMS: Stem cells from human exfoliated deciduous teeth (SHED) play a significant role in tissue engineering and regenerative medicine. Angiogenesis is crucial in tissue regeneration and a primary target of regenerative medicine. As a first-line anti-diabetic drug, metformin demonstrates numerous valuable impacts on stem cells. This study aimed to explore metformin's impact and mechanism of action on SHED-mediated angiogenesis. METHODS: First, cell proliferation; flow cytometry; osteogenic, adipogenic and chondrogenic induction; and proteomics analyses were conducted to explore the role of metformin in SHED. Subsequently, migration and tube formation assays were used to evaluate chemotaxis and angiogenesis enhancement by SHED pre-treated with metformin under co-culture conditions in vitro, and relative messenger RNA expression levels were determined by quantitative reverse transcription polymerase chain reaction. Finally, nude mice were used for in vivo tube formation assay, and sections were analyzed through immunohistochemistry staining with anti-human CD31 antibody. RESULTS: Metformin significantly promoted SHED proliferation as well as osteogenic, adipogenic and chondrogenic differentiation. Proteomics showed that metformin significantly upregulated 124 differentially abundant proteins involved in intracellular processes, including various proteins involved in cell migration and angiogenesis, such as MAPK1. The co-culture system demonstrated that SHED pre-treated with metformin significantly improved the migration and angiogenesis of human umbilical vein endothelial cells. In addition, SHED pre-treated with metformin possessed greater ability to promote angiogenesis in vivo. CONCLUSIONS: In summary, the authors' findings illustrate metformin's mechanism of action on SHED and confirm that SHED pre-treated with metformin exhibits a strong capacity for promoting angiogenesis. This helps in promoting the application of dental pulp-derived stem cells pre-treated with metformin in regeneration engineering.
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Metformina , Engenharia Tecidual , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Polpa Dentária , Células Endoteliais da Veia Umbilical Humana , Humanos , Metformina/farmacologia , Camundongos , Camundongos Nus , RNA Mensageiro/metabolismo , Células-Tronco , Dente DecíduoRESUMO
PURPOSE: Emotional control, the attempt to suppress the expression of negative effects, is an essential factor in the prevalence of psychological distress in women with breast cancer. The Courtauld Emotional Control Scale (CECS) is a commonly used self-report tool for assessing emotional suppression in both clinical and general groups. This study aimed to validate the Chinese version of the Courtauld Emotional Control Scale (CECS) in women newly diagnosed with breast cancer. METHODS: The study involved 680 women newly diagnosed with breast cancer aged 25 to 76 (mean age = 48.19, standard deviation (SD) = 8.57) from Changsha (China). Data analysis included Cronbach's alpha coefficients, the intraclass correlation coefficient (ICC), Pearson's correlations, Independent-Samples T test, confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM) were conducted to determine the optimal model. For the best fitting model stability was assessed with tests for invariance across age, educational level, and employment status. RESULTS: Internal consistency (α = 0.987) and test-retest reliability (ICC = 0.715) of the CECS were presented. Results confirm the structure of the Chinese version of the CECS with 21 items divided into three dimensions, anger suppression (CECS_AG), depression suppression (CECS_MD), and anxiety suppression (CECS_AX). Convergent and known-groups validity were acceptable. Additionally, this model remained invariant across age, educational levels, and employment status. CONCLUSIONS: The Chinese version of the CECS has good psychometric properties in terms of reliability and validity, remaining invariant across age, educational levels, and employment status in women newly diagnosed with breast cancer.
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Neoplasias da Mama , Adulto , Idoso , Neoplasias da Mama/psicologia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Psicometria/métodos , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Stem cells from human exfoliated deciduous teeth (SHED) can be used as a potential clinical material. But the use of xenogeneic ingredients will increase the risk of zoonotic disease transmission. Human platelet lysate (HPL) is a potential surrogate and used in human cell expansion with reliability in clinical applications. In this study, we synthesized chitosan/gelatin/gellan gum hydrogel supplemented with HPL and investigated the effect of 3D culture for SHED. TMT-tagged proteomics was used to decipher the secretome protein profiles of SHEDs and a total of 3209 proteins were identified, of which 23 were up-regulated and 192 were down-regulated. The results showed that hydrogel supplemented with HPL promoted SHED proliferation. After induction, the hydrogel coating contributed to osteogenic differentiation, adipogenic differentiation and differentiation into neural-like cells of SHED. SHED encapsulated in a hydrogel promotes migration and angiogenesis of HUVEC. In conclusion, our research found that hydrogel supplemented with HPL can be used as a method for SHED in standardized production and can contribute to the clinical application of SHED in cell therapy.
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Células-Tronco Mesenquimais , Osteogênese , Diferenciação Celular , Humanos , Hidrogéis/farmacologia , Reprodutibilidade dos TestesRESUMO
Human gingival mesenchymal stem cells (GMSCs) are derived from migratory neural crest stem cells and have the potential to differentiate into neurons. Metformin can inhibit stem-cell aging and promotes the regeneration and development of neurons. In this study, we investigated the potential of metformin as an enhancer on neuronal differentiation of GMSCs in the growth environment of chitosan hydrogel. The crosslinked chitosan/ß-glycerophosphate hydrogel can form a perforated microporous structure that is suitable for cell growth and channels to transport water and macromolecules. GMSCs have powerful osteogenic, adipogenic and chondrogenic abilities in the induction medium supplemented with metformin. After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron-like cells with a significantly enhanced expression of neuro-related markers, including Nestin (NES) and ß-Tubulin (TUJ1). Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1). Our results help to promote the clinical application of stem-cell neural regeneration.
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Quitosana , Células-Tronco Mesenquimais , Metformina , Diferenciação Celular , Células Cultivadas , Quitosana/química , Gengiva , Humanos , Hidrogéis/química , Células-Tronco Mesenquimais/metabolismo , Metformina/metabolismo , Metformina/farmacologia , NeurôniosRESUMO
Multiple myeloma (MM) is the second most common hematologic malignancy. MM stem cells (MMSCs) are thought to be the main causes of in vivo engraftment and eventual recurrence. As a notable new technology, cold atmospheric plasmas (CAPs) show a promising anti-tumor effect, due to their production of various ROS. In this study, we found that different types of plasma could inhibit MM's ability to form cell colonies, suppress MM in vivo engraftment, and extend survival times. We demonstrated that NAC (a ROS scavenger) could block ROS increases and reverse the inhibition of MM's cell-colony-formation ability, which was induced by the plasma treatment. By using a stem cell signaling array, we found that the Notch pathway was inhibited by the plasma treatment; this was further confirmed by conducting real-time PCRs of three MM cell lines. Together, these results constitute the first report of plasma treatment inhibiting MM in vivo engraftment and prolonging survival time by suppressing the Notch pathway via ROS regulation.
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Mieloma Múltiplo , Gases em Plasma , Linhagem Celular Tumoral , Humanos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Gases em Plasma/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
Prostate cancer with high Gleason grade is prone to metastasis, which is one of the factors that seriously threaten the survival of patients, and it is also a treatment difficulty. In this study, we first revealed the potential connection between TPX2 and prostate cancer metastasis. We found that TPX2 is highly expressed in high-grade prostate cancer and is significantly related to poor prognosis. Depletion of TPX2 can significantly inhibit cell activity and migration, and in vivo experiments show that knockdown of TPX2 can significantly inhibit tumor growth. In terms of mechanism, we found that knocking down TPX2 can inhibit the expression of CDK1, repress the phosphorylation of ERK/GSK3ß/SNAIL signaling pathway, and thereby inhibit tumor epithelial-mesenchymal transition. Subsequently, we found that after rescuing TPX2, all related proteins and phenotype changes were restored, and this effect can be inhibited by CDK1 inhibitor, RO-3306. Our findings suggest the potential of TPX2 as an important target in anti-tumor metastasis therapy, which is conducive to precision medicine for prostate cancer.
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Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Transição Epitelial-Mesenquimal , Glicogênio Sintase Quinase 3 beta/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias da Próstata/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Animais , Proteína Quinase CDC2/antagonistas & inibidores , Ciclo Celular , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/deficiência , Proteínas Associadas aos Microtúbulos/genética , Metástase Neoplásica/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Quinolinas/farmacologia , Tiazóis/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Glycemic control has become a focus of concern among diabetic patients. However, only 26.71% of patients achieved better glycemic control in China. Given the complexity of glycemic control, it is worth investigating the potential mechanisms between negative emotions and glycemic control. A total of 428 participants were recruited from a tertiary hospital (the number of hospital beds>500). They completed questionnaires consisting of demographics, Zung Self-Assessed Anxiety Scale(SAS), Zung Self-Assessed Depression Scale(SDS), and the Summary of Diabetes Self-Care Activities (SDSCA). HbA1 c was used to measure glycemic control. Descriptive analysis, Pearson correlation analysis, and Bootstrap analysis were conducted to analyze data. A total of 428 questionnaires were distributed, with 28 invalid questionnaires (93.46% were valid). Depression and self-care activities (exercise, medication) were associated with glycemic control. At the same time, the Bootstrap analysis revealed that self-care activities (exercise: standardized coefficient ß = 0.0181, p < 0.05, medication: standardized coefficient ß = 0.0211, p < 0.05) mediated the relationship between depression and glycemic control.
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Diabetes Mellitus Tipo 2 , Controle Glicêmico , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/terapia , Emoções , Humanos , Autocuidado , Inquéritos e QuestionáriosRESUMO
The wide spread of fake news has caused huge losses to both governments and the public. Many existing works on fake news detection utilized spreading information like propagators profiles and the propagation structure. However, such methods face the difficulty of data collection and cannot detect fake news at the early stage. An alternative approach is to detect fake news solely based on its content. Early content-based methods rely on manually designed linguistic features. Such shallow features are domain-dependent, and cannot easily be generalized to cross-domain data. Recently, many natural language processing tasks resort to deep learning methods to learn word, sentence, and document representations. In this paper, we propose a novel graph-based neural network model named SemSeq4FD for early fake news detection based on enhanced text representations. In SemSeq4FD, we model the global pair-wise semantic relations between sentences as a complete graph, and learn the global sentence representations via a graph convolutional network with self-attention mechanism. Considering the importance of local context in conveying the sentence meaning, we employ a 1D convolutional network to learn the local sentence representations. The two representations are combined to form the enhanced sentence representations. Then a LSTM-based network is used to model the sequence of enhanced sentence representations, yielding the final document representation for fake news detection. Experiments conducted on four real-world datasets in English and Chinese, including cross-source and cross-domain datasets, demonstrate that our model can outperform the state-of-the-art methods.
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Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. This study explored the mechanisms and effects of supraspinal spexin on inflammatory pain. The results from the mouse formalin test show that i.c.v. administration of spexin decreased licking/biting time during the late and early phases. The nonamidated spexin had no effect on pain response. The antinociception of spexin was blocked by galanin receptor 3 antagonist SNAP 37889. The Galr3 and Adcy4 mRNA levels in the brain were increased after injection with spexin. The antinociceptive effects of spexin were completely reversed by opioid receptor antagonist naloxone and κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride. Spexin up-regulated the dynorphin and κ-opioid receptor gene and protein expression. PCR array assay and real-time PCR analysis show that spexin up-regulated the mRNA level of the FBJ osteosarcoma oncogene (Fos). T-5224, the inhibitor of c FBJ osteosarcoma oncogene (c-Fos)/activator protein 1 (AP-1), blocked the increased mRNA level of Pdyn and Oprk1 induced by spexin. I.C.V. spexin (2.43 mg/kg) increased the number of c-Fos-positive neurons in most subsections of periaqueductal gray. In addition, in the acetic acid-induced writhing test, i.c.v. spexin produced an antinociceptive effect. Our results indicate that spexin might be a novel neuropeptide with an antinociceptive effect against acute inflammatory pain.
Assuntos
Analgésicos/administração & dosagem , Modelos Animais de Doenças , Inflamação/complicações , Nociceptividade/efeitos dos fármacos , Dor/prevenção & controle , Hormônios Peptídicos/administração & dosagem , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Camundongos , Dor/etiologia , Dor/metabolismo , Medição da Dor , Proteínas Proto-Oncogênicas c-fos/genéticaRESUMO
We explored the face classification processing mechanism in depressed patients, especially the biases of happy faces in face classification processing of depression. Thirty patients with the first episode of depression at the First Affiliated Hospital of Harbin Medical University were selected as the depression group, while healthy people matched for age, gender, and educational level were assigned to the control group. The Hamilton Depression Scale and Hamilton Anxiety Scale were used to select the subjects; then, we used the forced face classification paradigm to collect behavioral (response time and accuracy) and event-related potential (ERP) data of the subjects. The differences between the groups were estimated using a repeated measurement analysis of variance. The total response time of classified faces in the depression group was longer than that in the control group, the correct rate was lower, and the difference was statistically significant (P < 0.05). N170 component analysis demonstrated that the latency of the depression group was prolonged, and the difference was statistically significant (P < 0.05). When classifying happy faces, the depressed patients demonstrated a decrease in N170 amplitude and a prolongation of latency in some brain regions compared with the healthy individuals. The cognitive bias in depression may be due to prolonged processing of positive facial information and difficulty in producing positive emotional responses.
Assuntos
Encéfalo/fisiopatologia , Depressão/fisiopatologia , Transtorno Depressivo/fisiopatologia , Reconhecimento Facial/fisiologia , Adulto , Povo Asiático , China , Eletroencefalografia , Potenciais Evocados , Expressão Facial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cadmium (Cd) pollution in plastic shed soils has become increasingly severe, posing a great threat to human health and social stability. Phytoremediation of cadmium pollution is an environmentally friendly and inexpensive remediation method. In this study, maize (Zea mays L.) was selected as the phytoremediation crop by a potted method, and the bioavailability of cadmium was investigated by adding exogenous elemental sulfur. The relationships among the sulfur content, maize growth, cadmium accumulation, and soil parameters were systematically studied. The results showed that, with the supplement of sulfur, the soil pH and activities of soil enzymes (urease, catalase, and sucrase) decreased gradually, and the available heavy metals (Cd, Cr, Zn, and Cu) in soil showed an upward trend. The optimal cadmium enrichment was achieved under T2 by increasing both the biomass of the maize plant and the cadmium concentration in roots and stems. However, T3 and T4 significantly inhibited the growth of maize roots and shoots, leading to a much lower plant biomass compared with that of CK (sulfur-free treatment) and T2. In addition, the cumulative cadmium was not increased because of the low accumulation of cadmium in some parts of the plant. Correlation analyses showed that the sulfur content was negatively correlated with soil pH and maize biomass (P < 0.01), and the cadmium content of whole maize was positively correlated with the dry weight of maize (P < 0.05) and the cadmium content in roots and stems (P < 0.01). In summary, to optimize cadmium phytoremediation of the plastic shed soil, an appropriate concentration of sulfur should be selected in practical applications to ensure that the biomass of the maize is maximized, and the cadmium concentration in different parts of the maize is increased or stabilized.