Sampsonkastrup3619

Enrichment analysis revealed that differentially expressed genes of human OM-MSCs mainly participated in cell cycle regulation, secretin of cytokines and so on. Meanwhile, hypoxic condition significantly promoted proliferation and inhibited apoptosis of human OM-MSCs, following loss-of-function assays confirmed that lncRNA DARS-AS1 were involved in this regulatory process by hypoxic condition. Further prediction of targeted genes and the construction of lncRNA-miRNA-mRNA interaction network enriched the significance regarding the mechanism of DARS-AS1.

Altogether, these findings provided a new perspective for understanding the molecules expression patterns in hypoxia that contributed to corresponding phenotype alterations of OM-MSCs.

Altogether, these findings provided a new perspective for understanding the molecules expression patterns in hypoxia that contributed to corresponding phenotype alterations of OM-MSCs.

GnRH-DFF40 (gonadotropin releasing hormone-DNA fragmentation factor 40) humanized recombinant immunotoxin serves as a prospective candidate for targeted therapy of malignancies with over-expressed gonadotropin releasing hormone receptor (GnRHR). In this study, we attempted to generate a GnRH-based chimeric protein composed of human DFF40 fused with GnRH which encodes an apoptotic nuclease and specifically targets cancer cells displaying GnRH receptor overexpression.

A codon optimized, synthetic GnRH-DFF40 fusion gene and its single counterpart (DFF40) were constructed in pET28a expression vector. Cytotoxicity of these expressed proteins were evaluated on three breast cancer cell lines (MCF7, MDA-MB231, and SKBR3). The stability and biological activity of the recombinant proteins were investigated in the treated cell line and cell-free system. Also, the ability of this fusion and its single form in inducing apoptosis, and inhibiting metastasis and migration were evaluated by flow cytometry, migration assay and wound healing analysis, respectively. In silico analyses were also done to understand the specific interactions between GnRH and its receptor.

GnRH-DFF40 fusion protein and DFF40 were successfully expressed. The purified chimeric protein showed dose-dependent cytotoxicity against all three cell lines. The recombinant fusion protein was biologically active with nucleolytic functionality and apoptosis induction ability. Moreover, the fusion could inhibit the invasion property of MDA-MB-231 cells. In silico analysis also showed that four residues from GnRH domain and 11 GnRHR residues had the most interaction sites for specific targeted delivery of the immunotoxin in cancer cells.

Fusion construct could be a prospective candidate for targeted therapy of cancers upregulating GnRH receptor.

Fusion construct could be a prospective candidate for targeted therapy of cancers upregulating GnRH receptor.

Antiretroviral therapy (ART) controls viral replication but cannot eradicate an infected virus and restore the immune response of patients.

The gene expression profiles of whole blood, PBMCs, CD4+ and CD8+ T cells were obtained from GSE108297. Coexpression analysis was carried out to evaluate differentially expressed genes (DEGs) between strong and weak responder HIV controllers (HICs). Enrichment analysis was used to explore the biological functions of DEGs. The key genes with common DEGs were screened using the Lasso Cox model. Then, the immune scores of HICs and HAART were calculated by ssGSEA. The content of CD4+ and CD8+ T cells, key genes were verified by flow cytometry, RT-PCR and Western blot analysis.

DEGs were clustered into 24 coexpression modules. DEGs related to general immune responses had the highest correlation with strong responding HICs, while DEGs mainly related to the apoptotic process had the highest correlation with weak responder HICs. The hub genes CD8A and CCT2, as well as the key genes TMEM132C and S100A9, were DEGs in HICs and HARRT. The immune score and flow cytometry showed that CD4+ and CD8+ T cells of HICs were lower than those of HARRT in whole blood. Experiments confirmed the expression of key genes in HICs and HARRT.

The key genes identified in this study highlight the strong responder HICs features that to help the immune system control HIV-1 infection. These results will be useful for developing therapeutic targets.

The key genes identified in this study highlight the strong responder HICs features that to help the immune system control HIV-1 infection. These results will be useful for developing therapeutic targets.Beta-2 adrenergic receptors (β2-ARs) have important roles in the pathogenesis and treatment of chronic obstructive pulmonary disease (COPD). In recent years, progress has been made in the study of β2-ARs. Here, we introduce the basic concepts of β2-ARs, related pathways, as well as application of blockers/agonists of β2-ARs, and β2-AR autoantibodies in COPD. Drugs targeting the β2-AR are being developed rapidly, and we expect them to improve the symptoms and prognosis of COPD patients in the future.After spinal cord injury (SCI), intestinal dysfunction has a serious impact on physical and mental health, quality of life, and social participation. Recent data from rodent and human studies indicated that SCI causes gut dysbiosis. Remodeling gut microbiota could be beneficial for the recovery of intestinal function and motor function after SCI. However, few studies have explored SCI with focus on the gut microbiota and "microbiota-gut-brain" axis. In this review, the complications following SCI, including intestinal dysfunction, anxiety and depression, metabolic disorders, and neuropathic pain, are directly or indirectly related to gut dysbiosis, which may be mediated by "gut-brain" interactions. Furthermore, we discuss the research strategies that can be beneficial in this regard, including germ-free animals, fecal microbiota transplantation, probiotics, phages, and brain imaging techniques. The current microbial research has shifted from descriptive to mechanismal perspective, and future research using new technologies may further demonstrate the pathophysiological mechanism of association of SCI with gut microbiota, elucidate the mode of interaction of gut microbiota and hosts, and help develop personalized microbiota-targeted therapies and drugs based on microbiota or corresponding metabolites.

Dysregulated long non-coding RNA (lncRNA) expression is closely related to neuroinflammation, leading to multiple neurodegenerative diseases. In this study, we investigated the function and regulation of lncRNA AK148321 in neuroinflammation using an in vitro lipopolysaccharide (LPS)-stimulated BV2 microglial cell system.

Expression of AK148321 was analyzed by qPCR. Inflammatory cytokine expression levels were determined by ELISA assay. The interaction between AK148321, microRNA (miRNA), and its target gene was validated by luciferase reporter assay and RNA immunoprecipitation (RIP). Cell apoptosis was analyzed by Annexin V/PI staining.

LPS treatment suppressed AK148321 expression in BV2 cells. Overexpression of AK148321 inhibited LPS-induced BV2 microglial cell activation and decreased the expression of inflammatory cytokine TNF-α and IL-1β. AK148321 function as a competing endogenous RNA (ceRNA) by sponging microRNA-1199-5p (MiR-1199-5p). In LPS-stimulated BV2 cells, AK148321 exerted its inhibitory function via negatively modulating miR-1199-5p expression. Moreover, we identified that Heat Shock Protein Family A Member 5 (HSPA5) was a direct target of miR-1199-5p. RIP assay using the anti-Ago2 antibody further validated the relationship among AK148321, miR-1199-5p and HSPA5. The AK148321/miR-1199-5p/HSPA5 axis regulated the neuroinflammation in LPS-induced BV2 microglial cells. Microglial cell culture supernatant from LPS-stimulated, AK148321-overexpressing BV2 cells suppressed the cell apoptosis of mouse hippocampal neuronal cell HT22, while HSPA5 knockdown abrogated the suppression effect.

Our findings suggest that AK148321 alleviates neuroinflammation in LPS-stimulated BV2 microglial cells through miR-1199-5p/HSPA5 axis.

Our findings suggest that AK148321 alleviates neuroinflammation in LPS-stimulated BV2 microglial cells through miR-1199-5p/HSPA5 axis.Heart failure (HF) is a progressive, debilitating condition characterized, in part, by altered ionic equilibria, increased ROS production and impaired cellular energy metabolism, contributing to variable profiles of systolic and diastolic dysfunction with significant functional limitations and risk of premature death. We summarize current knowledge concerning changes of intracellular Na+ and Ca2+ control mechanisms during the disease progression and their consequences on mitochondrial Ca2+ homeostasis and the shift in redox balance. Absent existing biological data, our computational modeling studies advance a new 'in silico' analysis to reconcile existing opposing views, based on different experimental HF models, regarding variations in mitochondrial Ca2+ concentration that participate in triggering and perpetuating oxidative stress in the failing heart and their impact on cardiac energetics. In agreement with our hypothesis and the literature, model simulations demonstrate the possibility that the heart's redox status together with cytoplasmic Na+ concentrations act as regulators of mitochondrial Ca2+ levels in HF and of the bioenergetics response that will ultimately drive ATP supply and oxidative stress. The resulting model predictions propose future directions to study the evolution of HF as well as other types of heart disease, and to develop novel testable mechanistic hypotheses that may lead to improved therapeutics.Pathological cardiac remodeling, characterized by excessive deposition of extracellular matrix proteins and cardiac hypertrophy, leads to the development of heart failure. Meprin α (Mep1a), a zinc metalloprotease, previously reported to participate in the regulation of inflammatory response and fibrosis, may also contribute to cardiac remodeling, although whether and how it participates in this process remains unknown. Here, in this work, we investigated the role of Mep1a in pathological cardiac remodeling, as well as the effects of the Mep1a inhibitor actinonin on cardiac remodeling-associated phenotypes. We found that Mep1a deficiency or chemical inhibition both significantly alleviated TAC- and Ang II-induced cardiac remodeling and dysfunction. Mep1a deletion and blocking both attenuated TAC- and Ang II-induced heart enlargement and increases in the thickness of the left ventricle anterior and posterior walls, and reduced expression of pro-hypertrophic markers, including atrial natriuretic peptide (ANP), bbuted to cardiac remodeling. In light of our findings that blocking Mep1a can ameliorate cardiac remodeling via inhibition of cardiac hypertrophy, fibrosis, and inflammation, Mep1a may therefore serve as a strong potential candidate for therapeutic targeting to prevent cardiac remodeling.eIF3i, a 36-kDa protein, is a putative subunit of the eIF3 complex important for translation initiation of mRNAs. It is a WD40 domain-containing protein with seven WD40 repeats that forms a β-propeller structure with an important function in pre-initiation complex formation and mRNA translation initiation. In addition to participating in the eIF3 complex formation for global translational control, eIF3i may bind to specific mRNAs and regulate their translation individually. find more Furthermore, eIF3i has been shown to bind to TGF-β type II receptor and participate in TGF-β signaling. It may also participate in and regulate other signaling pathways including Wnt/β-catenin pathway via translational regulation of COX-2 synthesis. These multiple canonical and noncanonical functions of eIF3i in translational control and in regulating signal transduction pathways may be responsible for its role in cell differentiation, cell cycle regulation, proliferation, and tumorigenesis. In this review, we will critically evaluate recent progresses and assess future prospects in studying eIF3i.