Identifying and validating potential therapeutic targets for septic heart failure and the cardioprotective effects of lycorine.

BACKGROUND: Septic heart failure has been recognized as a puzzle since antiquity and poses a major challenge to modern medicine. Our previous work has demonstrated the potential effects of lycorine (LYC) on sepsis and septic myocardial injury. Nonetheless, further exploration is needed to elucidate the underlying cellular and molecular mechanisms. METHODS: In this study, we conducted transcriptome analysis and weighted gene co-expression network analysis (WGCNA) to identify the key genes and reveal the mechanism of LYC against septic heart failure. PURPOSE: This study aims to apply bioinformatic analysis and experimental validations to explore the protective effects and underlying mechanism of LYC on the cecal ligation and puncture (CLP)-induced sepsis model mice. RESULTS: Transcriptome analysis revealed the differentially expressed genes (DEGs) following LYC treatment. WGCNA analysis identified gene modules associated with LYC-mediated protection, with BCL3 emerging as a core gene within these modules. Notably, BCL3 was an overlapping gene of DEGs and WGCNA core genes induced by LYC treatment, and is highly negatively correlated with cardiac function indicator. In vivo and in vitro study further prove that LYC exerted a protective effect against septic myocardial injury through inhibiting BCL3. BCL3 siRNA ameliorated LPS-induced cardiac injury and inflammation, while BCL3 overexpression reversed the protective effect of LYC against LPS injury. CONCLUSION: In summary, our findings demonstrate the significant attenuation of septic myocardial disorder by LYC, with the identification of BCL3 as a pivotal target gene. This study is the first to report the role of BCL3 in sepsis and septic myocardial injury. Furthermore, the strategy for hub genes screening used in our study facilitates a comprehensive exploration of septic targets and reveals the potential targets for LYC effect. These findings may offer a new therapeutic strategy for the management of septic heart failure, highlighting the cardioprotective effect of LYC as adjunctive therapy for sepsis management.

Pterostilbene protects against H2 O2 -induced oxidative stress by regulating GAS6/Axl signaling in HL-1 cells.

Pterostilbene (PTE, trans-3,5-dimethoxy-4'-hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axl signaling pathway in cardiomyocytes. Hydrogen peroxide (H2 O2 )-induced oxidative stress HL-1 cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real-time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE's protective role. The results showed that PTE treatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H2 O2 -injured HL-1 cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE-mediated pleiotropic effects.

Isopropyl 3-(3,4-dihydroxyphenyl) 2-hydroxypropanoate protects septic myocardial injury via regulating GAS6/Axl-AMPK signaling pathway.

In a previous study, we used metabolomic techniques to identify a new metabolite of Danshen Dripping Pills called isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), which has potential as a drug candidate for cardiovascular diseases. This study aimed to explore the protective effects of IDHP against septic myocardial injury, as well as its molecular mechanism. Wild type or GAS6 knockout mice injured by cecal ligation and puncture (CLP) were used to observe the effect of IDHP. Here, we found that a specific concentration of IDHP (60 mg/kg) significantly increased the survival rate of septic mice to about 75 % at 72 h post CLP, and showed improvements in sepsis score, blood biochemistry parameters, cardiac function, and myocardial tissue damage. Furthermore, IDHP inhibited myocardial oxidative stress, inflammatory response, apoptosis, and mitochondrial dysfunction. Molecularly, we discovered that IDHP treatment reversed the CLP-induced downregulation of GAS6, Axl, and p-AMPK/AMPK expression. In addition, GAS6 knockout reversed the positive effect of IDHP in septic mice, indicated by more severe myocardial tissue damage, oxidative stress, inflammatory response, and mitochondrial dysfunction. GAS6 knockout also resulted in decreased levels of GAS6, Axl, and p-AMPK/AMPK. Taken together, our study provides evidence that IDHP has significant cardioprotective effects against sepsis by regulating the GAS6/Axl-AMPK signaling pathway. This finding has important therapeutic potential for treating sepsis.

Tough and Self-Healing Waterborne Polyurethane Elastomers via Dynamic Hydrogen Bonds Design for Flexible Conductive Substrate Applications.

Balancing the mechanical strength and self-healing performance of polyurethane (PU) remains a significant challenge in achieving excellent self-repairing PU materials. In this study, a self-healing waterborne PU elastomer was designed from a bionic concept by incorporating 2'-deoxythymidine (2'-dT) and isophorone diamine (IPDA) into the polymer chain. The loose stacking of IPDA's irregular cycloaliphatic structure resulted in the irregular arrangement of urethane bonds in the hard domain. The formation of sextuple hydrogen bonds between 2'-dT and urethane bonds, as well as quadruple hydrogen bonds between urethane bonds themselves, enhanced the mechanical properties of the material. The multiple hydrogen bonds can dissociate, recombine, and dissipate energy, thereby improving the material's repair capability. The hierarchical self-assembly of hydrogen bonds enabled the PU to achieve a tensile strength of 15.3 MPa and toughness of 100.75 MJ/m3. The prepared PU film is highly transparent and has a transmittance of more than 90%. Additionally, it can undergo rapid repair under high temperatures or under trace solvent conditions. When used as a flexible conductive substrate, it quickly restored the conductivity and enhanced the material's lifespan after surface damage. This environmentally friendly and self-healing waterborne PU elastomer will hold broad application prospects in the field of flexible electronic devices.

Exploring the experience of meaning-centered group psychotherapy among Chinese cancer patients during active treatment: a descriptive qualitative study.

Objective: Meaninglessness poses a significant psychological challenge for cancer patients, negatively affecting their quality of life and increasing the risk of suicide. Meaning-Centered Group Therapy (MCGP) is an intervention designed specifically to enhance the meaning of life of cancer patients. Extensive research has documented its effectiveness across various cultures and populations. However, limited research has been conducted on the subjective experiences and perspectives of participants engaged in MCGP. Thus, the purpose of this study was to employ a qualitative design to explore the experiences and viewpoints of Chinese cancer patients who have undergone MCGP. Methods: Within a two-week timeframe following the conclusion of MCGP, semi-structured interviews were administered to twenty-one participants who had engaged in the therapy. The interview data were transcribed and subjected to thematic analysis. Results: Four main themes were identified: (a) Self-perceived personal change, (b) Overall experience of group therapy, (c) Barriers to participation of MCGP, and (d) Suggestions for future interventions. Conclusion: Despite the barriers to participation in the MCGP process, the overall experience for Chinese cancer patients undergoing active treatment is valuable and positive, providing multiple benefits. Future studies could explore the adaptation of MCGP to a broader range of cancer populations and diverse study populations.

Non-targeted Profiling of Sea Buckthorn Fruit Oil Fingerprints from 3 Regions and Study on Its Antioxidant Activity.

This study investigated the chemical and volatile characteristics of sea buckthorn fruits from three different regions in China. The chemical composition of the volatile oil was determined by using a non-targeted gas chromatography and mass spectrometry (GC/MS) method and the differences in chemical composition among the three producing areas were compared by heatmap providing a visual basis for researchers. A total of 93 compounds were identified, including 52 compounds from the Northeast China, 51 from the Xinjiang region, and 37 from Inner Mongolia region. Then, the in vitro antioxidant activity of sea buckthorn fruit oil was measured using DPPH, ABTS, and SOD inhibition tests, and the results showed that sea buckthorn fruit oil in northeast China was the strongest antioxidant, followed by Inner Mongolia and Xinjiang. The results of the CCK-8 experiment indicated that within the tested concentration, there is no cell cytotoxicity of the essential oil in human umbilical vein endothelial cells (HUVECs) cells. The results could supply reference to distinguish sea buckthorn fruit from different production areas and, meanwhile, clarify the activity and safety of sea buckthorn oil.

Efficacy of meaning-centered group psychotherapy in Chinese patients with cancer: A randomized controlled trial.

OBJECTIVES: Meaninglessness is one of the most common psychological problems in cancer patients, which can lead to anxiety, depression and psychological distress, and diminished quality of life. Recent evidence indicates that meaning-centered group psychotherapy (MCGP) effectively enhances the meaning in life among cancer patients. This study aimed to evaluate the impact of MCGP on the meaning in life, post-traumatic growth, psychological distress, and fear of recurrence among Chinese cancer patients with a favorable prognosis. METHODS: Sixty-six cancer patients were randomly assigned to either the MCGP group (n = 33) or the control group (n = 33). Participants in the MCGP group underwent a 4-week, 8-session MCGP, while those in the control group received usual care. Meaning in life, post-traumatic growth, psychological distress, and fear of recurrence were assessed at both baseline and postintervention to evaluate the impact of the intervention. The intervention outcomes were analyzed using paired t-tests or analysis of covariance, as appropriate. RESULTS: Patients in the MCGP group demonstrated significant improvements in meaning in life, post-traumatic growth, and fear of recurrence from baseline to postintervention. In comparison to the control group, the MCGP group displayed positive effects on meaning in life and post-traumatic growth following the intervention. However, no significant effects were observed in terms of psychological distress and fear of recurrence. SIGNIFICANCE OF RESULTS: Our research offers evidence supporting the effectiveness of MCGP in enhancing meaning in life and post-traumatic growth among Chinese cancer patients with a favorable prognosis.

Comparative transcriptome analysis of unfractionated peripheral blood leukocytes after exercise in human.

Exercise has profound but variable effects on the immune system. However, only limited information exists about the changes of exercise-induced gene expression in whole immune cells. The aim of this study is to unravel the potential molecular changes of genes which are related to immunity after exercise. The raw expression data and corresponding clinical of GSE18966 were downloaded from Gene Expression Omnibus database. The differentially expressed genes between control group and treat groups were performed by in-house developed perl scripts. A total of 83 differentially expressed genes (DEGs) (|log2 FC|> 1, FDR < 0.05) were identified between control and treat group 1 (0 h after exercise), 128 DEGs (|log2 FC|> 1, FDR < 0.05) between control and treat group 2 (4 h after exercise), and there was no significant difference between control and treat group 3 (20 h after exercise). Next, we identified 51 overlapping genes between treat group 1 (0 h after exercise) and treat group 2 (4 h after exercise) using Venn analysis. Protein-protein interaction (PPI) network was constructed by Cytoscape 3.7.2, and nine hub genes (S100A12, FCGR3B, FPR1, VNN2, AQP9, MMP9, OSM, NCF4, HP) were identified. Finally, 9 hub genes were identified as the potential biomarkers of exercise using validation set (GSE83578) verification analysis. These hub genes might serve as potential molecular targets of monitoring exercise and training processes in the further.

Parents' Self-Development Socialization Goals and Chinese Adolescents' Academic Motivation: The Mediating Role of Parents' Autonomy Support.

The socialization goals parents hold for their adolescents, which reflect the qualities, skills, or behaviors they want their adolescents to acquire, play an important role in shaping adolescents' adjustment via parenting practices. Nevertheless, there is a lack of studies that examine the longitudinal implications of parents' socialization goals for adolescents' academic motivation, especially in non-Western cultures. Moreover, evidence is still scarce regarding the full process from parents' socialization goals to parenting practices and further to adolescents' academic adjustment. To address these gaps, the current two-wave longitudinal study spanning one year examined whether two critical socialization goals endorsed by parents in Chinese culture, namely self-development (i.e., parents wanting adolescents to be unique, autonomous, and self-assertive) and academic achievement socialization goals (i.e., parents wanting adolescents to achieve academic success), predicted Chinese adolescents' academic motivation over time via parents' autonomy support. Two hundred and eighty-five Chinese adolescents (Mean age = 12.29 years, SD = 0.64, range = 11-14, 51% girls) reported on perceived parental socialization goals and autonomy support, as well as different aspects of their own academic motivation (i.e., academic interest, mastery orientation, and persistent responses to academic failure). Results showed that perceived parents' self-development socialization goals positively predicted adolescents' academic motivation one year later, which was mediated by parents' increased autonomy support. The findings highlight the positive role of parents' self-development socialization goals in Chinese adolescents' academic adjustment in the changing society, and identify the underlying socialization processes via parenting practices.

Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas.

Background: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods. Methods: The bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed. Results: Bioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs. Conclusion: Siglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas.

Graphene Oxide/Styrene-Butadiene Latex Hybrid Aerogel with Improved Mechanical Properties by PEI Grafted GO and CNT.

Graphene oxide aerogel (GOA) has wide application prospects due to its low density and high porosity. However, the poor mechanical properties and unstable structure of GOA have limited its practical applications. In this study, polyethyleneimide (PEI) was used to graft onto the surface of GO and carbon nanotubes (CNTs) to improve compatibility with polymers. Composite GOA was prepared by adding styrene-butadiene latex (SBL) to the modified GO and CNTs. The synergistic effect of PEI and SBL, resulted in an aerogel with excellent mechanical properties, compressive resistance, and structural stability. When the ratio of SBL to GO and GO to CNTs was 2:1 and 7:3, respectively, the obtained aerogel performance was the best, and the maximum compressive stress was 784.35% higher than that of GOA. The graft of PEI on the surface of GO and CNT could improve the mechanical properties of the aerogel, with greater improvements observed with grafting onto the surface of GO. Compared with GO/CNT/SBL aerogel without PEI grafting, the maximum stress of GO/CNT-PEI/SBL aerogel increased by 5.57%, that of GO-PEI/CNT/SBL aerogel increased by 20.25%, and that of GO-PEI/CNT-PEI/SBL aerogel increased by 28.99%. This work not only provided a possibility for the practical application of aerogel, but also steered the research of GOA in a new direction.

The regulatory role of PI3K in ageing-related diseases.

Ageing is a physiological/pathological process accompanied by the progressive damage of cell function, triggering various ageing-related disorders. Phosphatidylinositol 3-kinase (PI3K), which serves as one of the central regulators of ageing, is closely associated with cellular characteristics or molecular features, such as genome instability, telomere erosion, epigenetic alterations, and mitochondrial dysfunction. In this review, the PI3K signalling pathway was firstly thoroughly explained. The link between ageing pathogenesis and the PI3K signalling pathway was then summarized. Finally, the key regulatory roles of PI3K in ageing-related illnesses were investigated and stressed. In summary, we revealed that drug development and clinical application targeting PI3K is one of the focal points for delaying ageing and treating ageing-related diseases in the future.

Identification of CCR2 as a hub in septic myocardial injury and cardioprotection of silibinin.

Myocardial injury is a serious complication of sepsis associated with high morbidity and mortality. Our previous work has confirmed that silibinin (SIL) alleviates septic myocardial injury, but the specific molecular mechanism has not been fully elucidated. This study aimed to identify its potential targets through network pharmacology combined with experimental verification. Firstly, a total of 29 overlapping genes between sepsis and SIL targets were obtained from RNA-seq analysis and the known databases. Subsequently, KEGG and GO analysis showed that these genes were enriched in immune response and cytokine-cytokine receptor interaction pathways. Notably, CCR2 was identified as an important candidate hub by protein-protein interaction analysis and molecular docking approach. In vivo experiments showed that SIL treatment significantly improved survival rate and cardiac function in septic mice, accompanied by decreased CCR2 expression. Moreover, in vitro experiments obtained the similar results. Especially, CCR2 siRNA attenuated inflammation response. In conclusion, this study systematically elucidated the key target of SIL in the treatment of septic myocardial injury. These findings provide valuable insights into the targets of sepsis and offer new avenues for exploring drug effect systematically.

Odd-even effect on the thermal conductivity of liquid crystalline epoxy resins.

Rapid developments in high-performance computing and high-power electronics are driving needs for highly thermal conductive polymers and their composites for encapsulants and interface materials. However, polymers typically have low thermal conductivities of ∼0.2 W/(m K). We studied the thermal conductivity of a series of epoxy resins cured by one diamine hardener and seven diepoxide monomers with different precise ethylene linker lengths (x = 2-8). We found pronounced odd-even effects of the ethylene linker length on the liquid crystalline order, mass density, and thermal conductivity. Epoxy resins with even x have liquid crystalline structure with the highest density of 1.44 g/cm3 and highest thermal conductivity of 1.0 W/(m K). Epoxy resins with odd x are amorphous with the lowest density of 1.10 g/cm3 and lowest thermal conductivity of 0.17 W/(m K). These findings indicate that controlling precise linker length in dense networks is a powerful route to molecular design of thermally conductive polymers.

Structurally Stable, High-Strength Graphene Oxide/Carbon Nanotube/Epoxy Resin Aerogels as Three-Dimensional Skeletal Precursors for Wave-Absorbing Materials.

Three-dimensional (3D) graphene oxide aerogel (GOA) is one of the best fillers for composites for microwave absorption. However, its further development has been hindered by the poor mechanical properties. Methodology to improve the mechanical properties of the aerogel remains an urgent challenge. Herein, graphene oxide/carbon nanotube/epoxy resin composite aerogel (GCEA) was successfully prepared by a facile method. The results showed that the prepared GCEA with the hierarchical and 3D cross-linked structures exhibited excellent compression performance, structural and thermal stability, high hydrophilicity, and microwave absorption. The prepared GCEA recovered from multiple large strain cycles without significant permanent deformation. The minimum reflection loss (RL) was -39.60 dB and the maximum effective absorption bandwidth (EAB) was 2.48 GHz. The development of the enhanced GO aerogels will offer a new approach to the preparation of 3D microwave-absorbing skeletal materials with good mechanical properties.

Parental Collectivism Goals and Chinese Adolescents' Prosocial Behaviors: The Mediating Role of Authoritative Parenting.

Prosocial behaviors are important indicators of positive social adjustment during adolescence in collectivistic cultures. Although parents play a central role in the process of cultural socialization, it remains unclear how culturally embedded parental goals for their children are related to adolescent prosocial development, especially in non-Western countries. Moreover, little is known about whether parenting practices serve as an underlying mechanism in linking parental goals and adolescents' prosocial behaviors. To address these issues, this two-wave longitudinal study investigated the associations between parental collectivism goals and Chinese adolescents' prosocial behaviors, with attention to the mediating role of authoritative parenting. Two hundred and eighty-five Chinese adolescents (51% girls; mean age = 12.29 years, SD = 0.64, range = 11-14) completed measures on parental collectivism goals, parenting practices, and their own prosocial behaviors. Results showed that adolescents' perceived parental collectivism goals positively predicted their prosocial behaviors one year later, which was partially mediated by authoritative parenting. Notably, the effects of perceived parental collectivism goals and authoritative parenting on adolescents' later prosocial behaviors were more salient when adolescents initially showed a lower level of prosocial behaviors. The findings highlight the positive effects of parental collectivism goals in promoting adolescent prosocial development via authoritative parenting in the Chinese context, and identify the subgroup of adolescents who may derive particular benefits from this process.

Identifying the role of parent-child conflict and intimacy in Chinese adolescents' psychological distress during school reopening in COVID-19 pandemic.

School reopening during COVID-19 can be a particularly stressful transition for many adolescents. However, little is known about the impact of parent-child relationships on adolescents' mental health during this transition. Using a 2-wave longitudinal design, this research examined the role of parent-child conflict and intimacy in adolescents' psychological distress after school reopening. Immediately before school reopening, 879 Chinese adolescents (mean age = 13.14 years, 51% girls) reported on their parent-child conflict and intimacy. They also reported on their depressive symptoms and anger problems before and 3 months after school reopening. Youth who reported higher levels of parent-child conflict and lower levels of parent-child intimacy before school reopening were more likely to show increased depressive symptoms and anger problems over time. Moreover, the moderating role of parent-child conflict and intimacy in the link between youth's perceived stress toward school reopening and psychological distress was investigated. Specifically, parent-child conflict moderated the impact of youth's perceived stress on their psychological distress, such that greater perceived stress was only linked with more psychological distress over time in families with higher levels of parent-child conflict, but not in families with lower levels of parent-child conflict. Taken together, the findings highlight the important role of parent-child relationships in shaping adolescent's mental health as they return to school, which provides key insights into reducing adolescents' psychological distress during the transition of school reopening in COVID-19 pandemic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Differential Associations Between Parents' Versus Children's Perceptions of Parental Socialization Goals and Chinese Adolescent Depressive Symptoms.

Although prior studies have demonstrated the associations between parental socialization goals and parenting practices, as well as parenting practices and adolescent depressive symptoms, respectively, research examining the comprehensive developmental pathways among these constructs (i. e., the path from parental socialization goals to parenting practices to adolescent depressive symptoms) is scarce, especially in the Chinese context. Grounded in the integrative model of parenting, this study investigated the associations between parental socialization goals and adolescent depressive symptoms by examining the indirect pathways through parents' autonomy support and psychological control as well as the moderating effect of educational stage. In Study 1, 345 Chinese adolescents and their primary caregivers completed a measure on parental socialization goals. Adolescents also reported on their depressive symptoms. Results showed that children who reported more self-development parental goals showed fewer depressive symptoms. However, parents' reports of goals or child-parent perceptual discrepancies were not related to children's depressive symptoms. Drawing on this finding, 424 middle school and 301 high school Chinese adolescents completed measures regarding parental socialization goals, autonomy support, psychological control, and their own depressive symptoms in Study 2. Results showed that parental autonomy support linked the associations of self-development and achievement-oriented parental goals and children's depressive symptoms among middle school students, whereas parental psychological control linked such associations among high school students. Our findings provide a more holistic view on how parents' socialization goals are related to children's depressive symptoms via their parenting practices. We also discussed the practical implications for the clinical work regarding adolescent depressive symptoms.

Serum-derived exosomes containing NEAT1 promote the occurrence of rheumatoid arthritis through regulation of miR-144-3p/ROCK2 axis.

BACKGROUND: Evidence has demonstrated that non-coding RNAs (ncRNAs) could be delivered efficiently to recipient cells using exosomes as a carrier. Additionally, long ncRNA nuclear enriched abundant transcript 1 (NEAT1) is emerging as a vital regulatory molecule in the progression of rheumatoid arthritis (RA). The aim of this study was to identify the NEAT1/miR-144-3p/Rho-associated protein kinase 2 (ROCK2) functional network regulating the WNT signaling pathway in RA. METHODS: In vivo, a collagen-induced arthritis (CIA) model was established to analyze the effects of blood exosomes on the incidence, clinical score, and bone degradation of RA. In vitro, the CD4+T cells were characterized by flow cytometry and the cell activities were analyzed in the presence of exosome treatment alone or in combination with altered expression of NEAT1, miR-144-3p or Rho-associated protein kinase 2 (ROCK2). The expression of NEAT1, miR-144-3p, ROCK2, and corresponding proteins in the WNT signaling pathway was detected by RT-qPCR and western blot techniques. The binding profile of NEAT1 to miR-144-3p was evaluated via a combination approach of luciferase activity assay, RNA immunoprecipitation, and RNA pull-down experiments. RESULTS: Blood exosomes extracted from RA patients increased the incidence of RA and bone destruction significantly. Overexpression of NEAT1 or ROCK2 promoted immune cell (CD4+T cells) proliferation, Th17 cell differentiation, and cell migration in response to stimulus, whereas knockout of the NEAT1 gene induced the expression of miR-144-3p in CD4+T cells. ROCK2 exogenous expression inhibited the expression of miR-144-3p, inducing activation of the WNT signaling pathway. CONCLUSION: A novel regulatory pathway NEAT1/miR-144-3p/ROCK2/WNT in RA was investigated as a potential target for RA therapy.

miR-373-3p inhibits epithelial-mesenchymal transition via regulation of TGFßR2 in choriocarcinoma.

AIM: Previous studies have indicated that early metastasis is a major cause of mortality in patients with choriocarcinoma. However, what determines whether early metastasis of choriocarcinoma has occurred is unknown. The emerging role of miRNA in regulating cancer development and progression has been recognized. miR-373 has been shown to play pivotal roles in tumorigenesis and metastasis. However, whether miR-373 functions to promote choriocarcinoma metastasis is not clear. The purpose of this study is to determine the function of miR-373-3p in the progression of this cancer. METHODS: In this study, we first compared epithelial-mesenchymal transition (EMT)-related markers, which were inversely correlated with miR-373-3p expression in trophoblast and choriocarcinoma cell lines. Using PCR and Western blot, upregulation of miR-373-3p was observed to inhibit EMT progression. Similarly, gain- and loss-of-function studies revealed that ectopic miR-373-3p overexpression inhibited the migration by transwell methods of choriocarcinoma cells. RESULTS: Our results revealed that miR-373-3p acted as an EMT inhibitor in JEG-3 and JAR cells; this was due to its mediation of the transforming growth factor-ß (TGFß) signaling pathway, which was responsible for EMT. miRNA microarray analysis demonstrated that miR-373-3p interacted with the 3' untranslated region of TGFßR2 mRNA, and then Western blot and dual-luciferase reporter gene assays verified this interaction. CONCLUSION: Our findings suggest that miR-373-3p upregulation partly accounts for TGFßR2 downregulation and leads to a restraint of EMT and migration. miR-373-3p may therefore serve as a valuable potential target in the treatment of choriocarcinoma.