Abstract Background and aims Long non-coding RNA (lncRNA) MEG3 has proven to be an important regulator involved in the pathogenesis and development of various human diseases. However, the functional ...involvement of MEG3 in postmenopausal osteoporosis (PMOP) and its mechanism is still unclear. Methods Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured from mouse pathologic models and patients with PMOP, respectively. The expression of MEG3 and miR-133a-3p in BMSCs was detected using qRT-PCR. The recombinant expression vector was constructed and transfected into BMSCs to regulate the endogenous expression of MEG3 and miR-133a-3p. The mineralized nodules formation, alkaline phosphatase (ALP) activity and Runx2, OCN, OPN expressions were used as specific markers for the differentiation of osteoblasts. Results The expressions of MEG3 and miR-133a-3p in BMSCs from PMOP were increased, and there was a positive correlation between MEG3 and miR-133a-3p expression in BMSCs. In the differentiation process from BMSCs to osteoblasts, the expressions of MEG3 and miR-133a-3p were markedly decreased, and MEG3 overexpression reversed the osteogenic induction-mediated downregulation of miR-133a-3p, which was accompanied by significant decline in SLC39A1 expression. Furthermore, miR-133a-3p silencing or upregulation eliminated the effects of MEG3 on the osteogenic differentiation of BMSCs through direct binding. Conclusions The research indicated that MEG3 regulated the expression of miR-133a-3p, and inhibited the osteogenic differentiation of BMSCs induced PMOP.
Because the extracellular matrix protein agrin is essential for neuromuscular junction formation and maintenance, we tested the hypothesis that autoantibodies against agrin are present in sera from ...patients with myasthenia gravis (MG).
We determined the presence of anti-agrin antibodies in 54 sera from patients with generalized MG using a solid-phase ELISA with purified mini-agrin protein. Thirty of the 54 sera were seronegative for antibodies against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK), 15 had elevated levels of anti-MuSK, and 9 had elevated levels of anti-AChR autoantibodies. Sixteen sera from healthy volunteers served as control.
Five sera with elevated levels of anti-agrin antibodies were identified. The concentration of the antibodies ranged between 0.04 and 0.12 nM. Four of the 5 agrin-positive sera were also positive for anti-MuSK, one was positive for anti-AChR, and 2 had elevated levels of anti-low-density lipoprotein receptor-related protein 4 (LRP4) autoantibodies. Some of the sera stained adult mouse neuromuscular junctions and reacted with native mini-agrin expressed in 293HEK cells.
The results provide evidence for agrin as a novel target protein for autoantibodies in patients with MG. Anti-agrin antibodies were always detected in combination with autoantibodies against MuSK, LRP4, or AChRs, indicating a high incidence of autoantibodies against several neuromuscular proteins in the agrin-positive MG cases.
Dynamic capabilities are crucial to the survival and development of enterprises in the BOP (Base/Bottom of the Pyramid, hereinafter BOP) market. The research focuses on the double-edged sword impact ...of relational embeddedness on dynamic capabilities
ambidextrous learning, that is moderate embeddedness facilitates dynamic capabilities while overembeddedness inhibits them. Furthermore, this study investigates whether human capital moderates the relationships between relational embeddedness and ambidextrous learning. Selecting 264 samples for empirical research, firstly, the results show that the relational embeddedness in the BOP cooperation network has an inverted U-shaped influence on ambidextrous learning and dynamic capabilities. Secondly, exploratory learning and exploitative learning play a mediating role in relational embeddedness and dynamic capabilities. Thirdly, prior experience plays a positive moderating role in relational embeddedness and exploitative learning. The conclusions facilitate understanding the antecedents of dynamic capabilities and the black box of "embeddedness paradox," and provide empirical evidence for adjusting the human capital of enterprises, enhancing the exploratory learning capability and exploitative learning capability, and coping with the overembeddedness effects.
Building materials stand as a crucial cornerstone in the realm of architecture in China. Enhancing the processing technologyof diverse building materials to effectively elevate the level of ...architectural art has emerged as a prominent research focus. Inlight of this, the paper develops an analysis model centered on the influence of architectural art, utilizing the Taurus searchalgorithm. The study delves into the impact of distinct processing technologies on the diversified artistic expression of buildings.
It commences with an analysis of the current state of building materials processing technologies and their connection toarchitectural art. Following this, the paper constructs an analysis model elucidating the influence of architectural art, examiningits effects on diversified artistic expression through experiments. Finally, by amalgamating established building materialsprocessing technology with experimental verification, the paper scrutinizes the actual efficacy of the analysis model forthe influence of architectural art based on the Taurus search algorithm. The experimental outcomes underscore the variedinfluence of different processing technologies on the diversity of artistic expression in buildings, showcasing the quantitativeevaluation capabilities of the impact analysis model. KCI Citation Count: 0
Autophagy is an essential component of host innate and adaptive immunity. Viruses have developed diverse strategies for evading or utilizing autophagy for survival. The response of the autophagy ...pathways to virus invasion is poorly documented. Here, we report on the induction of autophagy initiated by the pathogen receptor HSP90AA1 (heat shock protein 90 kDa α cytosolic, class A member 1) via the AKT-MTOR (mechanistic target of rapamycin)-dependent pathway. Transmission electron microscopy and confocal microscopy revealed that intracellular autolysosomes packaged avibirnavirus particles. Autophagy detection showed that early avibirnavirus infection not only increased the amount of light chain 3 (LC3)-II, but also upregulated AKT-MTOR dephosphorylation. HSP90AA1-AKT-MTOR knockdown by RNA interference resulted in inhibition of autophagy during avibirnavirus infection. Virus titer assays further verified that autophagy inhibition, but not induction, enhanced avibirnavirus replication. Subsequently, we found that HSP90AA1 binding to the viral protein VP2 resulted in induction of autophagy and AKT-MTOR pathway inactivation. Collectively, our findings suggest that the cell surface protein HSP90AA1, an avibirnavirus-binding receptor, induces autophagy through the HSP90AA1-AKT-MTOR pathway in early infection. We reveal that upon viral recognition, a direct connection between HSP90AA1 and the AKT-MTOR pathway trigger autophagy, a critical step for controlling infection.
Aim
Pre‐eclampsia (PE) is the usual complication during pregnancy. Long noncoding RNAs are essential regulatory factors in many diseases. Nevertheless, the role of LINC00511 in the development of PE ...has not been fully elucidated.
Methods
The expression of LINC00511, homeobox protein A7 (HOXA7) and miR‐31‐5p was determined by quantitative real‐time polymerase chain reaction. The levels of HOXA7 protein and autophagy‐related proteins were measured by western blot analysis. Besides, cell proliferation was evaluated using cell counting kit 8 and colony formation assays. The apoptosis and invasion of cells were detected via flow cytometry and transwell assay, respectively. Further, the interaction between miR‐31‐5p and LINC00511 or HOXA7 was confirmed by dual‐luciferase reporter assay.
Results
The LINC00511 and HOXA7 expression levels were decreased in placental tissues of PE patients, and the expression levels of both were positively correlated. LINC00511 knockdown suppressed proliferation, invasion and autophagy, while enhanced apoptosis in trophoblast cells. Meanwhile, the elevated HOXA7 expression promoted proliferation, invasion, autophagy, and inhibited the apoptosis of trophoblast cells. Besides, overexpression of HOXA7 also could reverse the effect of LINC00511 knockdown on the biological function of trophoblast cells. Further experiments confirmed that miR‐31‐5p could be sponged by LINC00511 and could target HOXA7. Also, miR‐31‐5p mimic could invert the promoting effect of LINC00511 overexpression on the biological function of trophoblast cells.
Conclusion
LINC00511 expression was crucial for maintaining the normal function of trophoblast cells, and the decreased its expression might promote the progress of PE, which might provide some theoretical strategies for reducing the development of PE.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a typical immunosuppressive virus causing a large economic impact on the swine industry. The structural protein GP5 of PRRSV plays a ...pivotal role in its pathogenicity and immune evasion. Virus-host interactions play a crucial part in viral replication and immune escape. Therefore, understanding the interactions between GP5 and host proteins are significant for porcine reproductive and respiratory syndrome (PRRS) control. However, the interaction network between GP5 and host proteins in primary porcine alveolar macrophages (PAMs) has not been reported. In this study, 709 GP5-interacting host proteins were identified in primary PAMs by immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis revealed that these proteins were involved in multiple cellular processes, such as translation, protein transport, and protein stabilization. Subsequently, immunoprecipitation and immunofluorescence assay confirmed that GP5 could interact with antigen processing and presentation pathways related proteins. Finally, we found that GP5 may be a key protein that inhibits the antigen processing and presentation pathway during PRRSV infection. The novel host proteins identified in this study will be the candidates for studying the biological functions of GP5, which will provide new insights into PRRS prevention and vaccine development.
One of the most significant diseases in the swine business, porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory problems in piglets and reproductive failure in sows. The ...PRRSV nucleocapsid (N) protein is essential for the virus’ assembly, replication, and immune evasion. Stages in the viral replication cycle can be impacted by interactions between the PRRSV nucleocapsid protein and the host protein components. Therefore, it is of great significance to explore the interaction between the PRRSV nucleocapsid protein and the host. Nevertheless, no information has been published on the network of interactions between the nucleocapsid protein and the host proteins in primary porcine alveolar macrophages (PAMs). In this study, 349 host proteins interacting with nucleocapsid protein were screened in the PRRSV-infected PAMs through a liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based proteomics approach. Bioinformatics analysis, which included gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes database enrichment, and a protein–protein interaction (PPI) network, revealed that the host proteins interacting with PRRSV-N may be involved in protein binding, DNA transcription, metabolism, and innate immune responses. This study confirmed the interaction between the nucleocapsid protein and the natural immune-related proteins. Ultimately, our findings suggest that the nucleocapsid protein plays a pivotal role in facilitating immune evasion during a PRRSV infection. This study contributes to enhancing our understanding of the role played by the nucleocapsid protein in viral pathogenesis and virus–host interaction, thereby offering novel insights for the prevention and control of PRRS as well as the development of vaccines.
In recent years, the outbreak of infectious disease caused by Zika virus (ZIKV) has posed a major threat to global public health, calling for the development of therapeutics to treat ZIKV disease. ...Here, we have described the different stages of the ZIKV life cycle and summarized the latest progress in the development of small-molecule inhibitors against ZIKV infection. We have also discussed some general strategies for the discovery of small-molecule ZIKV inhibitors.
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