Dissecting the role of cell signaling versus CD8+ T cell modulation in propranolol antitumor activity
AbstractPreclinical and early clinical mechanistic studies of antitumor activity from the beta-adrenergic receptor ( β-AR) blocker propranolol have revealed both cell signaling and immune function pathway effects. Intertumoral studies were performed using propranolol, a β1-AR selective agent (atenolol), and a β2-AR selective agent (ICI 118,551) in a preclinical in vivo model, as a step to dissect the contribution of cell signaling and CD8+ immunological effects on anticancer activity. We found that repression of β2-AR but not β1-AR signaling selectively suppressed cell viability and inhibited xenograft growth in vivo....
Source: Journal of Molecular Medicine - July 27, 2022 Category: Molecular Biology Source Type: research
mTOR-FABP4 signal is activated in brain arteriovenous malformations in humans
AbstractArteriovenous malformations (AVMs) are the most common types of cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. The dysfunction of endothelial cells has been postulated to play a role in the pathogenesis of brain AVMs. mTOR-FABP4 signal enhances the angiogenic responses of endothelial cells and is not activated in the normal cerebral vasculature. Herein, we investigated the hypothesis that the mTOR-FABP4 signal may be activated in brain AVMs. The abundance of molecules in mTOR-FABP4 signal expression was detected by immunohistochemistry and Western blotting; special expres...
Source: Journal of Molecular Medicine - July 25, 2022 Category: Molecular Biology Source Type: research
Cellular localization of nucleolin determines the prognosis in cancers: a meta-analysis
This study supports the role of subcellular NCL as a poor prognostic cancer biomarker. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - July 21, 2022 Category: Molecular Biology Source Type: research
Ataluren suppresses a premature termination codon in an MPS I-H mouse
AbstarctSuppressing translation termination at premature termination codons (PTCs), termed readthrough, is a potential therapy for genetic diseases caused by nonsense mutations. Ataluren is a compound that has shown promise for clinical use as a readthrough agent. However, some reports suggest that ataluren is ineffective at suppressing PTCs. To further evaluate the effectiveness of ataluren as a readthrough agent, we examined its ability to suppress PTCs in a variety of previously untested models. Using NanoLuc readthrough reporters expressed in two different cell types, we found that ataluren stimulated a significant lev...
Source: Journal of Molecular Medicine - July 20, 2022 Category: Molecular Biology Source Type: research
Aib1 deficiency exacerbates inflammatory responses in acute myocardial infarction mice
AbstractAcute myocardial infarction (AMI) is one of the major causes of death throughout the world, while inflammation has been known as a major contributor to the pathophysiology of AMI. Inhibition of inflammation is shown to protect from AMI. Amplified in breast 1 (Aib1) is a transcriptional coactivator protein which can suppress inflammation. The anti-inflammatory activities of Aib1 imply its potential effects against AMI; however, to date the role of Aib1 in AMI has not been described yet. Here we explored the potential functions of Aib1 in AMI. We induced AMI in both wild-type (WT) and Aib1−/− mice. The expression...
Source: Journal of Molecular Medicine - July 15, 2022 Category: Molecular Biology Source Type: research
MiR-30c-1-3p targets matrix metalloproteinase 9 involved in the rupture of abdominal aortic aneurysms
AbstractAbdominal aortic aneurysm (AAA) can be fatal if ruptured, but there is no predictive biomarker. Our aim was to evaluate the prognostic potential of microRNAs (miRNAs/miRs) in an AAA mouse model and patients with unruptured AAA (URAAA) and ruptured AAA (RAAA). Among the 64 miRNAs differentially expressed in mice with AAA compared to control, miR-30c-1-3p, miR-432-3p, miR-3154, and miR-379-5p had high homology with human miRNAs. MiR-30c-1-3p plasma levels were significantly lower in patients with RAAA than in those with URAAA or control and tended to negatively correlate with the maximum aortic diameter (r =  â...
Source: Journal of Molecular Medicine - July 15, 2022 Category: Molecular Biology Source Type: research
Progranulin, a moderator of estrogen/estrogen receptor α binding, regulates bone homeostasis through PERK/p-eIF2 signaling pathway
In this study, the serum estrogen levels were significantly increased in thegranulin (GRN) –deficient mice and PGRN regulates the binding of estrogen and estrogen receptor α (ERα) and then affects estrogen’s ability to regulate bone formation and resorption. In addition, this study also explored the role that PGRN plays in regulating bone homeostasis by affecting the binding of estr ogen and estrogen receptors through the protein kinase R-like endoplasmic reticulum kinase/phosphorylation of the eukaryotic initiation factor 2 signaling pathway. In summary, we confirmed the important role of PGRN in regulating the estr...
Source: Journal of Molecular Medicine - July 15, 2022 Category: Molecular Biology Source Type: research
Functional roles of E3 ubiquitin ligases in prostate cancer
AbstractProstate cancer (PCa) is a malignant epithelial tumor of the prostate gland with a high male cancer incidence. Numerous studies indicate that abnormal function of ubiquitin –proteasome system (UPS) is associated with the progression and metastasis of PCa. E3 ubiquitin ligases, key components of UPS, determine the specificity of substrates, and substantial advances of E3 ubiquitin ligases have been reached recently. Herein, we introduce the structures and functions of E3 ubiquitin ligases and summarize the mechanisms of E3 ubiquitin ligases-related PCa signaling pathways. In addition, some progresses in the develo...
Source: Journal of Molecular Medicine - July 11, 2022 Category: Molecular Biology Source Type: research
Glycosaminoglycan signatures in body fluids of mucopolysaccharidosis type II mouse model under long-term enzyme replacement therapy
AbstractMucopolysaccharidosis type II (MPS II) is a neurometabolic disorder, due to the deficit of the lysosomal hydrolase iduronate 2-sulfatase (IDS). This leads to a severe clinical condition caused by a multi-organ accumulation of the glycosaminoglycans (GAGs/GAG) heparan- and dermatan-sulfate, whose elevated levels can be detected in body fluids. Since 2006, enzyme replacement therapy (ERT) has been clinically applied, showing efficacy in some peripheral districts. In addition to clinical monitoring, GAG dosage has been commonly used to evaluate ERT efficacy. However, a strict long-term monitoring of GAG content and co...
Source: Journal of Molecular Medicine - July 11, 2022 Category: Molecular Biology Source Type: research
LncRNA GATA3-AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR-361/ARRB2 axis
AbstractEndometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used...
Source: Journal of Molecular Medicine - July 5, 2022 Category: Molecular Biology Source Type: research
Epigenetic mechanisms regulate sex-specific bias in disease manifestations
AbstractSex presents a vital determinant of a person ’s physiology, anatomy, and development. Recent clinical studies indicate that sex is also involved in the differential manifestation of various diseases, affecting both clinical outcome as well as response to therapy. Genetic and epigenetic changes are implicated in sex bias and regulate disease onset, including the inactivation of the X chromosome as well as sex chromosome aneuploidy. The differential expression of X-linked genes, along with the presence of sex-specific hormones, exhibits a significant impact on immune system function. Several studies have revealed d...
Source: Journal of Molecular Medicine - June 29, 2022 Category: Molecular Biology Source Type: research
Calorie restriction and breast cancer treatment: a mini-review
AbstractCalorie restriction (CR), referred to as a reduction in dietary calorie intake without malnutrition, has been demonstrated to be a safe way to extend longevity of yeast, worms, and laboratory animals, and to decrease the risk factors in age-related diseases including cancer in humans. Pre-clinical studies in animal models demonstrated that CR may enhance the efficacy of chemotherapy, radiation therapy, and immunotherapy during breast cancer treatment. Reduced calorie intake ameliorates risk factors and delays the onset of cancer by altering metabolism and fostering health-enhancing characteristics including increas...
Source: Journal of Molecular Medicine - June 27, 2022 Category: Molecular Biology Source Type: research
Retraction Note: Stabilization of the histone acetyltransferase Tip60 by deubiquitinating enzyme USP7 stimulates the release of pro-inflammatory mediators in acute lung injury
(Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - June 23, 2022 Category: Molecular Biology Source Type: research
Identification of KANSL1 as a novel pathogenic gene for developmental dysplasia of the hip
In conclusion, our findings suggest thatKANSL1 is a novel pathogenic gene for DDH. The identification ofKANSL1 variants has great diagnostic value for identifying individuals with DDH.Key messagesDevelopmental dysplasia of the hip (DDH) is a common anomaly causing adult osteoarthritis. Environmental and genetic factors contribute to DDH, but its exact genetic mechanism is unclear.Using high-throughput whole exome sequencing, we found a novel variant inKANSL1 that was co-inherited by all severely affected individuals diagnosed with DDH from a three-generation family. Further analysis revealed that aKansl1 variant in mice re...
Source: Journal of Molecular Medicine - June 21, 2022 Category: Molecular Biology Source Type: research
MyD88 in hepatic stellate cells promotes the development of alcoholic fatty liver via the AKT pathway
AbstractMyeloid differentiation primary response gene 88 (MyD88), an adaptor protein in the Toll-like receptors (TLRs) signalling pathway, is expressed in various liver cells including hepatocytes, Kupffer cells and hepatic stellate cells (HSCs). And yet, the functional role of MyD88 in HSCs is poorly elucidated in alcoholic fatty liver (AFL). Here, to study the functional role of MyD88 in HSCs and the molecular mechanism related to the development of AFL, chronic-binge ethanol mouse models were established in mice with specific MyD88 knockout in quiescent (MyD88GFAP −KO) and activated HSCs (MyD88SMA −KO), respectively...
Source: Journal of Molecular Medicine - June 16, 2022 Category: Molecular Biology Source Type: research
