Accumulating evidence indicates the significant role of lncRNAs in multiple biological processes and cancer progression. However, most lncRNAs in CRC remain to be excavated. In this study, we investigated SNHG14 in CRC. SNHG14 which was generally under-expressed in normal colon specimens revealed by UCSC was uncovered as markedly highly expressed in CRC cell lines. Besides, SNHG14 was a contributor to CRC cell proliferation. Additionally, we demonstrated that SNHG14 facilitated CRC cell proliferation in a KRAS-dependent manner. Moreover, the mechanistic investigations indicated that SNHG14 interacted with YAP and therefore inactivated the Hippo pathway, so as to enhance YAP-targeted KRAS expression in CRC. Furthermore, SNHG14 was explained as transcriptionally activated by FOS, a previously identified common effector molecule of KRAS and YAP. All in all, our findings elucidated a feedback loop of SNHG14/YAP/KRAS/FOS in facilitating CRC tumorigenesis, which may help develop novel effective targets for CRC patients.
Traumatic brain injury (TBI) refers to brain dysfunction with or without traumatic structural injury induced by an external force. Nevertheless, the molecular mechanism of TBI remains undefined. Differentially expressed (DE) lncRNAs, DEmRNAs and DEmiRNAs were selected between human TBI tissues and the adjacent histologically normal tissue by high-throughput sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis of overlapping DEmRNAs between predicted mRNAs of DEmiRNAs and DEmRNAs. The competitive endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA was established in light of the ceRNA theory. In the ceRNA network, the key lncRNAs were screened out. Then key lncRNAs related ceRNA subnetwork was constructed. After that, qRT-PCR was applied to validate the expression levels of hub genes. 114 DElncRNAs, 1807 DEmRNAs and 6 DEmiRNAs were DE in TBI. The TBI-related ceRNA network was built with 73 lncRNA nodes, 81 mRNA nodes and 6 miRNAs. According to topological analysis, two hub lncRNAs (ENST00000562897 and ENST00000640877) were selected to construct the ceRNA subnetwork. Subsequently, key lncRNA-miRNA-mRNA regulatory axes constructed by two lncRNAs including ENST00000562897 and ENST00000640877, two miRNAs including miR-6721-5p and miR-129-1-3p, two mRNAs including ketohexokinase (KHK) and cyclic nucleotide-gated channel beta1 (CNGB1), were identified. Furthermore, qRT-PCR results displayed that the expression of ENST00000562897, KHK and CNGB1 were significantly decreased in TBI, while the miR-6721-5p expression levels were markedly increased in TBI. The results of our study reveal a new insight into understanding the ceRNA regulation mechanism in TBI and select key lncRNA-miRNA-mRNA axes for prevention and treatment of TBI.
Background & Aim: Non-suicidal self-injury (NSSI) in adolescents is a serious public health issue influenced by the interaction of multiple factors. The purpose of this study was to investigate the multiple mediating roles of alexithymia and self-esteem in the association between bullying victimization and NSSI in a sample of Chinese adolescents. Methods: A survey of 1299 adolescents from two public middle schools in Henan Province, China, was undertaken. Data were collected using the Chinese version of the Delaware bullying victimization scale-student (DBVS-S), the Toronto Alexithymia-20 Scale (TAS-20-C), the Rosenberg self-esteem scale (RSES), and the adolescent self-injury questionnaire. Besides, we performed a structural equation modeling (SEM) with latent variables using AMOS 26.0 to examine the relationship between variables and the mediating effects. Results: The SEM analysis found that not only can bullying victimization directly impact NSSI, but that alexithymia and self-esteem have a chain mediating effect in the association between bullying victimization and NSSI. This mediating effect contributed 22.47% to the total effect. Conclusion: These findings validate bullying victimization, alexithymia, and low self-esteem are important variables that affect NSSI among Chinese adolescents. Educators need to implement some prevention and intervention strategies to ameliorate the campus atmosphere and adolescents' mental health aimed at avoiding NSSI behavior in adolescence. Keywords: bullying victimization, non-suicidal self-injury, alexithymia, self-esteem, adolescents
Premature ovarian insufficiency (POI) may lead to early menopause, fertility loss and birth defects without effective treatment. Here, we explored the efficacy and safety of gene therapy to rescue ovarian function in both natural ovarian aging and doxorubicin (Dox) induced POI mice. Sirt1 and Tgfbr2 were screened out and identified as key genes in both murine and human ovarian tissues. Then, adenovirus (AdV) was selected as a suited carrier for ovarian infection after comparison of multiple viral vectors. In both two models, murine fertility was significantly improved after AdV-Sirt1 and AdV-Tgfbr2 invention individually or in combination, without obvious side effects to themselves and their offspring. Compared with the control group, the successful pregnancy rate in the 9-month-old-AdV-Sirt1 group increased by 60 % (67 % vs 42 %). Meanwhile, the pregnancy rate in the AdV-Tgfbr2 + Dox group increased by 85 % (55.6 % vs 20 %). The biological process of ovarian follicle development and fibrosis was rescued. Our work demonstrated that AdV-Sirt1 and AdV-Tgfbr2 therapy alleviates natural ovarian aging and Dox-associated POI, which may be potentially applicable for female fertility protection.
Ultraviolet (UV) irradiation leads to the degradation of the extracellular matrix and collagen, thereby accelerating skin aging and imposing substantial psychological burden on patients. Current anti-aging strategies are limited and often associated with high costs or strong side effects. Plant-derived extracellular vesicle-like nanovesicles, with advantages such as natural availability and cost-effectiveness, show potential in anti-aging interventions. This study extracted extracellular vesicle-like nanovesicle from Polygonum multiflorum (PMELNVs) and systematically investigated their composition and metabolic pathways, further examining their efficacy and underlying mechanisms in combating photoaging. Results revealed the excellent antioxidative properties of PMELNVs, alleviating UV-induced oxidative stress, inhibiting matrix metalloproteinase production, reducing extracellular matrix degradation, promoting collagen synthesis, and ultimately exerting anti-photoaging effects. Additionally, safety assessments demonstrated favorable biocompatibility of PMELNVs. This study provides novel evidence supporting PMELNVs’ ability to resist photoaging by reducing oxidative stress and enhancing collagen expression, thereby offering potential as a new natural therapeutic agent against skin photoaging and promising a safer and more effective local anti-aging strategy.
Marine organisms are a rich source of enzymes that exhibit excellent biological activity and a wide range of applications. However, there has been limited research on the proteases found in marine mudflat organisms. Based on this background, the marine fibrinolytic enzyme FELP, which was isolated and purified from clamworm (Perinereis aibuhitensis), has exhibited excellent fibrinolytic activity. We demonstrated the FELP with a purification of 10.61-fold by precipitation with ammonium sulfate, ion-exchange chromatography, and gel-filtration chromatography. SDS-PAGE, fibrin plate method, and LC–MS/MS indicated that the molecular weight of FELP is 28.9 kDa and identified FELP as a fibrinolytic enzyme-like protease. FELP displayed the maximum fibrinolytic activity at pH 9 (407 ± 16 mm2) and 50 °C (724 ± 27 mm2) and had excellent stability at pH 7–11 (50%) or 30–60 °C (60%), respectively. The three-dimensional structure of some amino acid residues of FELP was predicted with the SWISS-MODEL. The fibrinolytic and fibrinogenolytic assays showed that the enzyme possessed direct fibrinolytic activity and indirect fibrinolysis via the activation of plasminogen; it could preferentially degrade Aα-chains of fibrinogen, followed by Bβ- and γ-chains. Overall, the fibrinolytic enzyme was successfully purified from Perinereis aibuhitensis, a marine Annelida (phylum), with favorable stability that has strong fibrinolysis activity in vitro. Therefore, FELP appears to be a potent fibrinolytic enzyme with an application that deserves further investigation.
The thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator in the balance between blood clot formation (coagulation) and dissolution (fibrinolysis), which is mainly activated by thrombin bonded with thrombomodulin (TM).
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