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PubMed Journal Database | Journal of molecular medicine (Berlin, Germany) RSS

04:15 EST 26th February 2020 | BioPortfolio

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Showing PubMed Articles 1–25 of 94 from Journal of molecular medicine (Berlin, Germany)

ASK1 inhibition: a therapeutic strategy with multi-system benefits.

p38 mitogen-activated protein kinases (P38α and β) and c-Jun N-terminal kinases (JNK1, 2, and 3) are key mediators of the cellular stress response. However, prolonged P38 and JNK signalling is associated with damaging inflammatory responses, reactive oxygen species-induced cell death, and fibrosis in multiple tissues, such as the kidney, liver, central nervous system, and cardiopulmonary systems. These responses are associated with many human diseases, including arthritis, dementia, and multiple organ dys...

AVE0991, a nonpeptide angiotensin-(1-7) mimic, inhibits angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E knockout mice.

AVE0991, a nonpeptide angiotensin-(1-7) mimic, has similar protective effects for cardiovascular system to Ang-(1-7). In this article, we aimed to explore the effects of AVE0991 and Ang-(1-7) on abdominal aortic aneurysm (AAA) induced by Ang II in apolipoprotein E knockout mice. The mice AAA model was established by Ang II infusion, and then mice received different treatment with saline, Ang II (1.44 mg/kg/day), different dose AVE0991 (0.58 or 1.16 μmol/kg/day), or Ang-(1-7) (400 ng/kg/min). The inciden...

RIG-I aggravates interstitial fibrosis via c-Myc-mediated fibroblast activation in UUO mice.

Progressive tubulointerstitial fibrosis is the common final outcome for all kidney diseases evolving into chronic kidney disease (CKD), whereas molecular mechanisms driving fibrogenesis remain elusive. Retinoic acid-inducible gene-I (RIG-I), an intracellular pattern recognition receptor, is originally identified participating in immune response by recognizing virus RNA. Here, we revealed for the first time that RIG-I was induced in unilateral ureteral obstruction (UUO) and folic acid (FA) renal fibrosis mod...

Exploring the role of high-mobility group box 1 (HMGB1) protein in the pathogenesis of Huntington's disease.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by an increased and unstable CAG DNA expansion in the Huntingtin (HTT) gene, resulting in an elongated polyglutamine tract in huntingtin protein. Despite its monogenic cause, HD pathogenesis remains elusive and without any approved disease-modifying therapy as yet. A growing body of evidence highlights the emerging role of high-mobility group box 1 (HMGB1) protein in HD pathology. HMGB1, being a nuclear protein, is primaril...

Altered molecular signatures during kidney development after intrauterine growth restriction of different origins.

This study was performed to identify transcriptional alterations in male intrauterine growth restricted (IUGR) rats during and at the end of nephrogenesis in order to generate hypotheses which molecular mechanisms contribute to adverse kidney programming. IUGR was induced by low protein (LP) diet throughout pregnancy, bilateral uterine vessel ligation (LIG), or intrauterine stress (IUS) by sham operation. Offspring of unimpaired dams served as controls. Significant acute kidney damage was ruled out by negat...

Correction to: Surface anchorage of superantigen SEA promotes induction of specific antitumor immune response by tumor-derived exosomes.

The corrected Fig. 1 image and caption is presented in this paper.

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.

The integrated stress response promotes B7H6 expression.

The B7 family member, B7H6, is a ligand for the natural killer cell receptor NKp30. B7H6 is hardly expressed on normal tissues, but undergoes upregulation on different types of tumors, implicating it as an attractive target for cancer immunotherapy. The molecular mechanisms that control B7H6 expression are poorly understood. We report that in contrast to other NK cell ligands, endoplasmic reticulum (ER) stress upregulates B7H6 mRNA levels and surface expression. B7H6 induction by ER stress requires protein ...

Gene-environment regulatory circuits of right ventricular pathology in tetralogy of fallot.

The phenotypic spectrum of congenital heart defects (CHDs) is contributed by both genetic and environmental factors. Their interactions are profoundly heterogeneous but may operate on common pathways as in the case of hypoxia signaling during postnatal heart development in the context of CHDs. Tetralogy of Fallot (TOF) is the most common cyanotic (hypoxemic) CHD. However, how the hypoxic environment contributes to TOF pathogenesis after birth is poorly understood. We performed Genome-wide transcriptome ana...

Selective protection of murine cerebral G-proteins from inactivation by parenterally injected pertussis toxin.

Pertussis toxin (PTX) is a potent virulence factor in patients suffering from whooping cough, but in its detoxified version, it is applied for vaccination. It is thought to contribute to the pathology of the disease including various CNS malfunctions. Based on its enzymatic activity, PTX disrupts GPCR-dependent signaling by modifying the α-subunit of heterotrimeric G-proteins. It is also extensively used as a research tool to study neuronal functions in vivo and in vitro. However, data demonstrating the pe...

Heterologous prime-boost vaccination against tuberculosis with recombinant Sendai virus and DNA vaccines.

In an earlier study, a novel Sendai virus-vectored anti-tuberculosis vaccine encoding Ag85A and Ag85B (SeV85AB) was constructed and shown to elicit antigen-specific T cell responses and protection against Mycobacterium tuberculosis (Mtb) infection in a murine model. In this study, we evaluate whether the immune responses induced by this novel vaccine might be elevated by a recombinant DNA vaccine expressing the same antigen in a heterologous prime-boost vaccination strategy. The results showed that both SeV...

Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation.

MCPIP1 (Regnase-1, encoded by the ZC3H12A gene) regulates the mRNA stability of several inflammatory cytokines. Due to the critical role of this RNA endonuclease in the suppression of inflammation, Mcpip1 deficiency in mice leads to the development of postnatal multiorgan inflammation and premature death. Here, we generated mice with conditional deletion of Mcpip1 in the epidermis (Mcpip1). Mcpip1 loss in keratinocytes resulted in the upregulated expression of transcripts encoding factors related to inflamm...

Serum starvation enhances nonsense mutation readthrough.

Of all genetic mutations causing human disease, premature termination codons (PTCs) that result from splicing defaults, insertions, deletions, and point mutations comprise around 30%. From these mutations, around 11% are a substitution of a single nucleotide that change a codon into a premature termination codon. These types of mutations affect several million patients suffering from a large variety of genetic diseases, ranging from relatively common inheritable cancer syndromes to muscular dystrophy or ver...

Co-delivery of GOLPH3 siRNA and gefitinib by cationic lipid-PLGA nanoparticles improves EGFR-targeted therapy for glioma.

Glioblastoma 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)...

Autophagy plays a critical role in Klotho gene deficiency-induced arterial stiffening and hypertension.

Klotho is an anti-aging gene that shortens the life span when disrupted and extends the lifespan when overexpressed. This study investigated whether autophagy plays a role in Klotho gene deficiency-induced arterial stiffening and hypertension. Klotho mutant heterozygous (KL+/-) mice and age- and sex-matched wild-type (WT) mice were used. Arteries were examined for autophagy using Western blot assays. Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) increased signifi...

Clinical relevance of circadian melatonin release in relapsing-remitting multiple sclerosis.

A growing body of evidence indicates the role of melatonin (MT) in the pathogenesis of multiple sclerosis (MS): It modulates immune function, alleviates oxidative stress and it is linked to seasonality of MS relapse. This report addresses the potential clinical relevance of circadian MT rhythms in relapsing-remitting MS (RRMS) patients. The study sample comprised of fifty-five RRMS patients and fifty age- and sex-matched healthy control (HC) subjects. Circadian salivary MT was measured non-invasively at 12 ...

Adipose-derived stromal cell secretome disrupts autophagy in glioblastoma.

Mesenchymal stromal cells (MSCs) are frequently recruited to tumor sites to play a part in the tumor microenvironment (TME). However, their real impact on cancer cell behavior remains obscure. Here we investigated the effects of human adipose-derived stromal cell (hADSC) secretome in autophagy of glioblastoma (GBM), as a way to better comprehend how hADSCs influence the TME. GBM U-87 MG cells were treated with conditioned medium (CM) from hADSCs and autophagic flux was evaluated. hADSC CM treatment blocked ...

Correction to: PRSS21/testisin inhibits ovarian tumor metastasis and antagonizes proangiogenic angiopoietins ANG2 and ANGPTL4.

The affiliation of Erik W. Martin is corrected in this paper.

Delayed endometrial decidualisation in polycystic ovary syndrome; the role of AR-MAGEA11.

Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, with a prevalence of up to 12% of women of reproductive age, and is in part characterised by elevated circulating androgens and aberrant expression of androgen receptor (AR) in the endometrium. A high percentage of PCOS patients suffer from infertility, a condition that appears to be linked to mistimed and incomplete decidualisation critically affecting events surrounding embryo implantation. The aim of this study was to examine the invol...

Critical regulation of atherosclerosis by the KCa3.1 channel and the retargeting of this therapeutic target in in-stent neoatherosclerosis.

Coronary heart disease is a serious cardiovascular illness. Percutaneous coronary artery stent implantation has become a routine way to treat coronary heart disease. Although studies have shown how a drug-eluting stent could improve the efficacy of clinical treatment, 10~20% of in-stent restenosis is still an important outcome that restricts the clinical efficacy of drug-eluting stent implantations and causes cardiovascular events such as angina pectoris, acute myocardial infarction, and sudden death. The K...

A non-beta-lactam antibiotic inhibitor for enterohemorrhagic Escherichia coli O104:H4.

The overuse of antibiotics has caused an increased prevalence of drug-resistant bacteria. Bacterial resistance in E. coli is regulated via production of β-lactam-hydrolyzing β-lactamases enzymes. Escherichia coli O104: H4 is a multi-drug resistant strain known to resist β-lactam as well as several other antibiotics. Here, we report a molecular dynamic simulation-combined docking approach to identify, screen, and verify active pharmacophores against enterohemorrhagic Escherichia coli (EHEC). Experimental ...

Relevance of VEGFA in rat livers subjected to partial hepatectomy under ischemia-reperfusion.

We examined the effects of VEGFA on damage and regeneration in steatotic and non-steatotic livers of rats submitted to PH under I/R, and characterized the underlying mechanisms involved. Our results indicated that VEGFA levels were decreased in both steatotic and non-steatotic livers after surgery. The administration of VEGFA increased VEGFA levels in non-steatotic livers, reducing the incidence of post-operative complications following surgery through the VEGFR2-Wnt2 pathway, independently of Id1. Unexpect...

Preclinical studies of a death receptor 5 fusion protein that ameliorates acute liver failure.

Acute liver failure (ALF) is a life-threatening disease with a high mortality rate. There is an urgent need to develop new drugs with high efficacy and low toxicity. In this study, we produced a pharmaceutical-grade soluble death receptor 5 (sDR5)-Fc fusion protein for treating ALF and evaluated the pharmacology, safety, pharmacokinetics, efficacy, and mechanisms of sDR5-Fc in mice, rats, and cynomolgus monkeys. sDR5-Fc bound with high affinity to both human and monkey tumor necrosis factor-related apoptosi...

Correction to: Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis.

In Figure 7f the panel for c-myc of MDA-MB-468 was erroneously duplicated. The corrected version of the figure is shown in this paper. This correction does not influence the conclusion of the study and we sincerely apologize for this oversight.

Combination of PARP inhibitor and temozolomide to suppress chordoma progression.

Chordoma, a malignant bone cancer, is highly resistant to conventional therapeutic approaches; this greatly limits radio- and chemotherapeutic options and disease management. In the present study, we investigated three patient-derived chordoma cell lines to elucidate the molecular mechanism of resistance to therapeutics. An in vitro high-throughput chemical screening assay and an in vivo xenograft model were used to identify novel chemosensitizers for chordoma. We found that patient-derived chordoma cell li...


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