Institutt for medisinsk biologi: Nye registreringer
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Antibiotikaresistens - globalt, lokalt, i dag och i morgon
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-09)Antibiotikaresistensen ökar kraftigt, och i dag pågår ett internationellt samarbete för att motverka detta. Antibiotikaförskrivningen i tandvården i de nordiska länderna är ur ett internationellt perspektiv låg. Det finns dock en del indikationer på att denna kan reduceras ytterligare. -
Tandvårdsturism - ökad risk för folkhälsan
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-09)Så kallad medicinsk turism, att kombinera elektiv vård utomlands med semester, ökar kraftigt. Medicinsk turism kan skapa såväl kulturella, ekonomiska, etiska, legala och medicinska problem genom import av smittsamma sjukdomar till hemlandet. Patienter som väljer att söka vård utomlands bör vara införstådda med att det kan medföra en ökad risk att bli infekterad av antibiotikaresistenta bakterier. -
Tumor lysis with LTX-401 creates anticancer immunity
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-13)Local immunotherapies such as the intratumoral injection of oncolytic compounds aim at reinstating and enhancing systemic anticancer immune responses. LTX-315 is a first-in-class, clinically evaluated oncolytic peptide-based local immunotherapy that meets these criteria. Here, we show that LTX-401, yet another oncolytic compound designed for local immunotherapy, depicts a similar safety profile and ... -
NIMA-related kinase 9–mediated phosphorylation of the microtubule-associated LC3B protein at Thr-50 suppresses selective autophagy of p62/sequestosome 1
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-19)Human ATG8 family proteins (ATG8s) are active in all steps of the macroautophagy pathway, and their lipidation is essential for autophagosome formation. Lipidated ATG8s anchored to the outer surface of the phagophore serve as scaffolds for binding of other core autophagy proteins and various effector proteins involved in trafficking or fusion events, whereas those at the inner surface are needed for ... -
Detection of tissue factor in platelets: why is it so troublesome?
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-05-30)Tissue factor (TF) is the most important trigger for the extrinsic coagulation pathway. TF, earlier denoted as thromboplastin, has always been a mystery since its discovery due to its abundant presence in most human tissues but not blood. The latter has been extensively studied in a vast quest for possible sources of blood-borne TF yielding many conflicting findings and confusing conclusions regarding ... -
LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-14)LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug’s mode of action in vivo. We report LTX-315 mediates profound ... -
Murine models for studying treatment, prevention and pathogenesis of FNAIT
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-31)Maternal alloimmunization to paternally inherited antigens on fetal/neonatal platelets can cause fetal/neonatal alloimmune thrombocytopenia (FNAIT) after antibody-mediated removal of platelets from the fetal circulation. The complications vary from mild bleeding symptoms to severe intracranial hemorrhage and subsequent neurological impairment or death. Studies on <i>in vivo</i> mechanisms are ... -
Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-23)Pivmecillinam, a pro-drug of mecillinam, has been used extensively in Scandinavia for the treatment of acute lower urinary tract infections (UTIs) caused by Enterobacterales. It is still an attractive first-line drug for the empirical treatment of UTIs owing to the low prevalence of resistance as well as its favourable impact on the intestinal microbiota as a pro-drug and good in vitro efficacy ... -
Microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections caused by ESBL‐producing Escherichia coli
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-22)The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections (ca‐UTIs) caused by ESBL‐producing Escherichia coli. Eighty‐nine ESBL‐producing E. coli isolated from women suffering from ca‐UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was ... -
Inflammatory serum markers and risk and severity of prostate cancer: The PROCA‐life study
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-03)Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive‐CRP (hs‐CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA‐<i>life</i>), a prospective population‐based cohort study, 7,356 men were included. Prediagnostic WBC and hs‐CRP were assessed ... -
Altered mitochondrial metabolism in the insulin-resistant heart
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-16)Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function ... -
MCPyV Large T antigen induced atonal homolog 1 (ATOH1) is a lineage-dependency oncogene in Merkel cell carcinoma.
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-07)Despite the fact that the transcription factor ATOH1 is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependent oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, which is one of the most ... -
Liver sinusoidal endothelial cells contribute to the uptake and degradation of entero bacterial viruses
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-21)The liver is constantly exposed to dietary antigens, viruses, and bacterial products with inflammatory potential. For decades cellular uptake of virus has been studied in connection with infection, while the few studies designed to look into clearance mechanisms focused mainly on the role of macrophages. In recent years, attention has been directed towards the liver sinusoidal endothelial cells ... -
NIPSNAP1 and NIPSNAP2 Act as “Eat Me” Signals for Mitophagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-11)The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease. Our understanding of the mitochondrial signals that trigger their recognition and targeting by mitophagy is limited. Here, we show that the mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog ... -
Combined Therapy With Dobutamine and Omecamtiv Mecarbil in Pigs With Ischemic Acute Heart Failure Is Attributed to the Effect of Dobutamine
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-23)Inotropic support in ischemic acute heart failure (AHF) is controversial. We tested a therapeutic principle for AHF by combining a low dose of omecamtiv mecarbil (OM; 0.25 mg/kg bolus plus 0.25 mg/kg/h) with a low dose of dobutamine (Dobut; 1.25 µg/kg/min). In 10 pigs subjected to myocardial ischemia by left coronary microembolization, this cotreatment increased cardiac power (CP) from 0.48 ± 0.14 ... -
Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-23)Accumulating evidence suggests that constitutively active Nrf2 has a pivotal role in cancer as it induces pro-survival genes that promote cancer cell proliferation and chemoresistance. The mechanisms of Nrf2 dysregulation and functions in cancer have not been fully characterized. Here, we jointly analyzed the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Atlas (TCGA) ... -
TAK1 converts Sequestosome 1/p62 from an autophagy receptor to a signaling platform
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-25)The protein p62/Sequestosome 1 (p62) has been described as a selective autophagy receptor and independently as a platform for pro‐inflammatory and other intracellular signaling. How these seemingly disparate functional roles of p62 are coordinated has not been resolved. Here, we show that TAK1, a kinase involved in immune signaling, negatively regulates p62 action in autophagy. TAK1 reduces p62 ... -
Selective Autophagy: RNA Comes from the Vault to Regulate p62/SQSTM1
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-22)A new study shows that the oligomerization of p62/Sequestosome-1 (SQSTM1) — a selective autophagy receptor and signaling adapter — is regulated directly by vault RNA. This riboregulation negatively affects the aggregation state of p62 and thereby its autophagic degradation and its role as a selective autophagy receptor. -
Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-13)Selective autophagy relies on soluble or membrane-bound cargo receptors that recognize cargo and bring about autophagosome formation at the cargo. The cargo-bound receptors interact with lipidated ATG8 family proteins anchored in the membrane at the concave side of the forming autophagosome. The interaction is mediated by 15- to 20-amino-acid-long sequence motifs called LC3-interacting region (LIR) ... -
Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-18)Mammalian homologs of yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains ill‐defined. Syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was recently shown to bind mAtg8s. Here, we identified LC3‐interacting regions (LIRs) in several SNAREs that broaden the landscape of the mAtg8‐SNARE interactions. We found that Syntaxin 16 (Stx16) and its cognate ...