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Source: Journal of Molecular Medicine
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Total 44 results found since Jan 2013.
Suppression of PGE2/EP2 signaling alleviates Hirschsprung disease by upregulating p38 mitogen-activated protein kinase activity
In this study, anEdnrb-deficient mouse model of HSCR was generated and used to investigate if PGE2/EP2 pathway could be a potential therapeutic target for HSCR. We found that downregulation of PGE2/EP2 signaling by siRNA-mediated ablation of a PGE2 synthase or pharmacologic blockage of EP2 enhanced ENCC colonization in the distal bowel ofEdnrb−/− mice and alleviated their HSCR-like symptoms. Furthermore, blockage of EP2 was shown to promote ENCC migration through upregulating p38 mitogen-activated protein kinase activity, which was downregulated in the colon ofEdnrb−/− mice and in the distal aganglionic bowel of HS...
Source: Journal of Molecular Medicine - July 31, 2023 Category: Molecular Biology Source Type: research
CREB-H is a stress-regulator of hepcidin gene expression during early postnatal development
In conclusion, CREB-H has a role in maintaining the homeostatic balance of iron traffic through hepcidin during the critical postnatal period and in response to iron challenge.Key messagesCREB-H KO mice develop liver iron overload shortly after weaning that normalizes in adulthood.CHEB-H is involved in hepcidin gene response to oral iron in vivo.CREB-H loss hampers hepcidin promoter response to BMP6.CREB-H is a key stress-sensor controlling hepcidin gene transcription in physiologic and pathophysiologic states.
Source: Journal of Molecular Medicine - July 26, 2023 Category: Molecular Biology Source Type: research
TRIM-containing 44 aggravates cardiac hypertrophy via TLR4/NOX4-induced ferroptosis
This study explored the role of TRIM44 on pressure overload-induced cardiac hypertrophy in mice. Mice were subjected to aortic banding to establish an adverse cardiac hypertrophy model, followed by the administration of AAV9-TRIM44 or AAV9shTRIM44 to overexpress or knock down TRIM44. Echocardiography was used to assess cardiac function. H9c2 cells were cultured and transfected with either Ad-TRIM44 or TRIM44 siRNA to overexpress or silence TRIM44. Cells were also stimulated with angiotensin II to establish a cardiomyocyte hypertrophy model. Results indicated that TRIM44 was downregulated in mice hearts and cardiomyocytes t...
Source: Journal of Molecular Medicine - April 29, 2023 Category: Molecular Biology Source Type: research
Zinc finger and BTB domain-containing protein 20 aggravates angiotensin II-induced cardiac remodeling via the EGFR-AKT pathway
AbstractZinc finger and BTB domain-containing protein 20 (ZBTB20) play an important role in glucose and lipid homeostasis. ZBTB20 was shown to be a crucial protein for the maintenance of cardiac contractile function. However, the role of ZBTB20 in cardiac response remodeling has not been elucidated. Thus, this study aimed to explore the role of ZBTB20 in cardiac remodeling following angiotensin II insult. Mice were subjected to angiotensin II infusion to induce a cardiac adverse remodeling model. An adeno-associated virus (AAV) 9 system was used to deliver ZBTB20 to the mouse heart. Here, we demonstrate that ZBTB20 express...
Source: Journal of Molecular Medicine - July 7, 2021 Category: Molecular Biology Source Type: research
Silencing of Mcl-1 overcomes resistance of melanoma cells against TRAIL-armed oncolytic adenovirus by enhancement of apoptosis
AbstractArming of oncolytic viruses with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown as a viable approach to increase the antitumor efficacy in melanoma. However, melanoma cells may be partially or completely resistant to TRAIL or develop TRAIL resistance, thus counteracting the antitumor efficiency of TRAIL-armed oncolytic viruses. Recently, we found that TRAIL resistance in melanoma cells can be overcome by inhibition of antiapoptotic Bcl-2 protein myeloid cell leukemia 1 (Mcl-1). Here, we investigated whether the cytotoxicity of AdV-TRAIL, an oncolytic adenovirus, which expresses TRAIL...
Source: Journal of Molecular Medicine - May 24, 2021 Category: Molecular Biology Source Type: research
Tyrosine kinase Fyn promotes apoptosis after intracerebral hemorrhage in rats by activating Drp1 signaling
This study clarifies the relationship between Fyn, apoptosis, and inflammation following ICH and provides a new strategy for explo ring the prevention and treatment of ICH.Key messagesICH induced an increase in Fyn expression in human and rat cerebral tissues.Knockdown of Fyn prevented cerebral damage following ICH.Inhibition of Fyn had no significant effects on inflammatory responses. However, the downregulation of Fyn exerted neuroprotective effects on apoptosis.Fyn perturbed ICH-induced cell apoptosis by interacting with and phosphorylating (Ser616) Drp1 in a rat ICH model.
Source: Journal of Molecular Medicine - January 6, 2021 Category: Molecular Biology Source Type: research
NLRP3 inflammasome priming and activation in cholestatic liver injury via the sphingosine 1-phosphate/S1P receptor 2/G α (12/13) /MAPK signaling pathway
AbstractNLRP3 inflammasome-driven inflammation represents a key trigger for hepatic fibrogenesis during cholestatic liver injury. However, whether sphingosine 1-phosphate (S1P) plays a role in NLRP3 inflammasome priming and activation remains unknown. Here, we found that the expression of NLRP3 in macrophages and NLRP3 inflammasome activation were significantly elevated in the liver injured by bile duct ligation (BDL). In vitro, S1P promoted the NLRP3 inflammasome priming and activation via S1P receptor 2 (S1PR2) in bone marrow –derived monocyte/macrophages (BMMs). Focusing on BMMs, the gene silencing of Gα12 or G α13 ...
Source: Journal of Molecular Medicine - January 2, 2021 Category: Molecular Biology Source Type: research
Strategies for simultaneous and successive delivery of RNA
AbstractAdvanced non-viral gene delivery experiments often require co-delivery of multiple nucleic acids. Therefore, the availability of reliable and robust co-transfection methods and defined selection criteria for their use in, e.g., expression of multimeric proteins or mixed RNA/DNA delivery is of utmost importance. Here, we investigated different co- and successive transfection approaches, with particular focus on in vitro transcribed messenger RNA (IVT-mRNA). Expression levels and patterns of two fluorescent protein reporters were determined, using different IVT-mRNA doses, carriers, and cell types. Quantitative param...
Source: Journal of Molecular Medicine - November 4, 2020 Category: Molecular Biology Source Type: research
Autotaxin stimulates LPA2 receptor in macrophages and exacerbates dextran sulfate sodium-induced acute colitis
AbstractAutotaxin (ATX) is a secreted enzyme that hydrolyzes lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA) and choline. ATX has been implicated in multiple chronic inflammatory diseases, but little is known about its role in the development of inflammatory bowel disease (IBD). Here, we investigated how ATX contributed to intestinal inflammation during colitis. We found that ATX expression levels were upregulated in the intestines of ulcerative colitis (UC) patients in acute state as well as in the intestines of dextran sulfate sodium (DSS)-induced colitis mice, which is likely due to increased infiltration o...
Source: Journal of Molecular Medicine - October 31, 2020 Category: Molecular Biology Source Type: research
Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps
AbstractNumerous studies have shown that microbiomes play an important role in the pathogenesis of chronic rhinosinusitis (CRS). In addition to a known short pentraxin, C-reactive protein, long pentraxin 3 (PTX3) belongs to pentraxin family which detects conserved microbial pentraxin motifs and mobilizes early defense against foreign invaders, but its participation in CRS remains unclear. In the present study, through an intensive screening, peptidoglycan (PGN) was selected as a main material to investigate the action mechanism of a cell wall component on CRS without nasal polyps (CRSsNP) nasal mucosa-derived fibroblasts a...
Source: Journal of Molecular Medicine - April 1, 2020 Category: Molecular Biology Source Type: research
Correction to: Co-delivery of GOLPH3 siRNA and gefitinib by cationic lipid-PLGA nanoparticles improves EGFR-targeted therapy for glioma
The correct affiliation no 2 is presented in this paper.
Source: Journal of Molecular Medicine - January 2, 2020 Category: Molecular Biology Source Type: research
Co-delivery of GOLPH3 siRNA and gefitinib by cationic lipid-PLGA nanoparticles improves EGFR-targeted therapy for glioma
AbstractGlioblastoma is one of the most aggressive types of brain tumor. Epidermal growth factor receptors (EGFRs) are overexpressed in glioma, and EGFR amplifications and mutations lead to rapid proliferation and invasion. EGFR-targeted therapy might be an effective treatment for glioma. Gefitinib (Ge) is an EGFR tyrosine kinase inhibitor (TKI), and Golgi phosphoprotein 3 (GOLPH3) expression is associated with worse glioma prognosis. Downregulation of GOLPH3 could promote EGFR degradation. Here, an angiopep-2 (A2)-modified cationic lipid-poly (lactic-co-glycolic acid) (PLGA) nanoparticle (A2-N) was developed that can rele...
Source: Journal of Molecular Medicine - October 29, 2019 Category: Molecular Biology Source Type: research
Dimethylaminomicheliolide ameliorates peritoneal fibrosis through the activation of autophagy
This study aimed to investigate the protective effect of DMAMCL against PD-related PF and the mechanisms involved. In this study, we found that DMAMCL significantly decreased PD-induced extracellular matrix (ECM) deposition in a mouse model of PD, and that delayed DMAMCL administration halted the progression of PF in an established PD model. In addition, rapamycin administration induced autophagy and significantly ameliorated PF. The protective effect of DMAMCL against PF was weakened when co-administered with DMAMCL and 3-methyladenine. Inducing autophagy by rapamycin decreased transforming growth factor- β1–induced EC...
Source: Journal of Molecular Medicine - March 10, 2019 Category: Molecular Biology Source Type: research
MicroRNA-145 targets Smad1 in endometrial stromal cells and regulates decidualization in rat
In conclusion, the study demonstrated the role of miR-145 in regulation of progression of decidualization which is mediated through inhibition of Smad1.Key messagesMiR-145 expression is downregulated during decidualization in the rat uterus.Overexpression of miR-145 inhibited the decidualization progression.MiR-145 suppressed the migration and invasion of HUVECs.MiR-145 downregulated Smad1 which suppresses Smad1/5/8, Wnt-4, MMP-9, Cox-2, and VEGF.
Source: Journal of Molecular Medicine - February 7, 2019 Category: Molecular Biology Source Type: research
Effect of DJ-1 on the neuroprotection of astrocytes subjected to cerebral ischemia/reperfusion injury
AbstractAstrocytes are involved in neuroprotection, and DJ-1 is an important antioxidant protein that is abundantly expressed in reactive astrocytes. However, the role of DJ-1 in astrocytes ’ neuroprotection in cerebral ischemia/reperfusion injury and its potential mechanism is unclear. Thus, to explore effects and mechanisms of DJ-1 on the neuroprotection of astrocytes, we used primary co-cultures of neurons and astrocytes under oxygen and glucose deprivation/reoxygenation in vitro and transient middle cerebral artery occlusion/reperfusion in vivo to mimic ischemic reperfusion insult. Lentiviral was used to inhibit and ...
Source: Journal of Molecular Medicine - November 30, 2018 Category: Molecular Biology Source Type: research
