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Article ; Online: Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-Analysis.

Clausen, Max / Christensen, Rune H B / da Re, Maria / Benros, Michael E

2024

Abstract: Background: A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with ...

Abstract	Background: A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking. Methods: Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included. Results: A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, -0.04 to 0.32). Conclusions: The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking.
Language	English
Publishing date	2024-01-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2023.11.029
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Article ; Online: Safety and Feasibility of Photodynamic Therapy for Percutaneous Image-guided Abdominopelvic Abscess Drainage: Phase 1 Trial.

Baran, Timothy M / Bass, David A / Christensen, Laurie / Longbine, Erica / Favella, Maria D / Foster, Thomas H / Sharma, Ashwani K

Radiology

2024 Volume 310, Issue 3, Page(s) e232667

Abstract: Background Standard-of-care abscess management includes image-guided percutaneous drainage and antibiotics; however, cure rates vary, and concern for antibiotic-resistant bacteria is growing. Photodynamic therapy (PDT), which uses light-activated dyes to ...

Abstract	Background Standard-of-care abscess management includes image-guided percutaneous drainage and antibiotics; however, cure rates vary, and concern for antibiotic-resistant bacteria is growing. Photodynamic therapy (PDT), which uses light-activated dyes to generate cytotoxic reactive oxygen species, could complement the standard of care by sterilizing the abscess at the time of drainage. Purpose To evaluate safety and feasibility of PDT with methylene blue (hereafter, MB-PDT) at the time of percutaneous abscess drainage. Materials and Methods This prospective, open-label, dose-escalation, first-in-humans, registered phase 1 clinical study of MB-PDT included participants who underwent percutaneous abdominal or pelvic abscess drainage with CT or US guidance from January 2015 to March 2020 and September 2022 to September 2023. Following drainage, MB-PDT was performed with laser illumination at a fluence rate of 20 mW/cm
MeSH term(s)	Female ; Humans ; Middle Aged ; Abscess/diagnostic imaging ; Abscess/drug therapy ; Anti-Bacterial Agents ; Drainage ; Feasibility Studies ; Photochemotherapy ; Prospective Studies ; Male ; Adult ; Aged
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	80324-8
ISSN	1527-1315 ; 0033-8419
ISSN (online)	1527-1315
ISSN	0033-8419
DOI	10.1148/radiol.232667
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Article ; Online: Pupillary dilation velocity is reduced in intensive care unit patients with septic shock.

Uhrenholt, Stine / Linér, Signe Maria / Stokholm, Jannik / Christensen, Thomas / Bestle, Morten H

Acta anaesthesiologica Scandinavica

2023 Volume 68, Issue 1, Page(s) 56–62

Abstract: Background: Septic shock is common in the intensive care unit (ICU). The pathophysiology is poorly understood but prolonged sympathetic activation leading to autonomic dysfunction may be involved. Pupillary light response (PLR) is a fast, inexpensive, ... ...

Abstract	Background: Septic shock is common in the intensive care unit (ICU). The pathophysiology is poorly understood but prolonged sympathetic activation leading to autonomic dysfunction may be involved. Pupillary light response (PLR) is a fast, inexpensive, noninvasive way to measure autonomic nervous system function. The aim of the study was to observe dilation velocity of the PLR (PLR Results: Ninety-one patients were enrolled and of these, 35 were in septic shock. Septic shock was associated with a slowed PLR Conclusions: Septic shock may be associated with changes in sympathetic autonomic tone which is supported by the findings from this study that septic shock was associated with a slower dilation velocity in the pupillary light reflex. Further studies should examine if the pupillary dilation velocity may serve as surrogate marker for changes in sympathetic autonomic nervous system activity in intensive care patients in septic shock. If so, future interventional studies should test if use of the pupillary dilation velocity may be used for earlier detection of septic shock, which could mean earlier institution of treatment measures for this condition.
MeSH term(s)	Adult ; Humans ; Shock, Septic/complications ; Prospective Studies ; Dilatation ; Critical Care ; Intensive Care Units
Language	English
Publishing date	2023-09-18
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	80002-8
ISSN	1399-6576 ; 0001-5172
ISSN (online)	1399-6576
ISSN	0001-5172
DOI	10.1111/aas.14327
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Article ; Online: Shared and Distinct Renal Transcriptome Signatures in 3 Standard Mouse Models of Chronic Kidney Disease.

Marstrand-Jørgensen, Adam B / Sembach, Frederikke Emilie / Bak, Stine Thorhauge / Ougaard, Maria / Christensen-Dalsgaard, Mikkel / Rønn Madsen, Martin / Jensen, Ditte Marie / Secher, Thomas / Heimbürger, Sebastian Møller Nguyen / Fink, Lisbeth N / Hansen, Ditte / Hansen, Henrik H / Østergaard, Mette Viberg / Christensen, Michael / Dalbøge, Louise S

Nephron

2024 , Page(s) 1–16

Abstract: Introduction: Several mouse models with diverse disease etiologies are used in preclinical research for chronic kidney disease (CKD). Here, we performed a head-to-head comparison of renal transcriptome signatures in standard mouse models of CKD to ... ...

Abstract	Introduction: Several mouse models with diverse disease etiologies are used in preclinical research for chronic kidney disease (CKD). Here, we performed a head-to-head comparison of renal transcriptome signatures in standard mouse models of CKD to assess shared and distinct molecular changes in three mouse models commonly employed in preclinical CKD research and drug discovery. Methods: All experiments were conducted on male C57BL/6J mice. Mice underwent sham, unilateral ureter obstruction (UUO), or unilateral ischemic-reperfusion injury (uIRI) surgery and were terminated two- and 6-weeks post-surgery, respectively. The adenine-supplemented diet-induced (ADI) model of CKD was established by feeding with adenine diet for 6 weeks and compared to control diet feeding. For all models, endpoints included plasma biochemistry, kidney histology, and RNA sequencing. Results: All models displayed increased macrophage infiltration (F4/80 IHC) and fibrosis (collagen 1a1 IHC). Compared to corresponding controls, all models were characterized by an extensive number of renal differentially expressed genes (≥11,000), with a notable overlap in transcriptomic signatures across models. Gene expression markers of fibrosis, inflammation, and kidney injury supported histological findings. Interestingly, model-specific transcriptome signatures included several genes representing current drug targets for CKD, emphasizing advantages and limitations of the three CKD models in preclinical target and drug discovery. Conclusion: The UUO, uIRI, and ADI mouse models of CKD have significant commonalities in their renal global transcriptome profile. Model-specific renal transcriptional signatures should be considered when selecting the specific model in preclinical target and drug discovery.
Language	English
Publishing date	2024-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000535918
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Article ; Online: Effect of Systemic Administration of CD4

Christensen, Pernille Kf / Hansen, Axel K / Skov, Søren / Larsen, Jesper / Høyer-Hansen, Maria H / Koch, Janne

Comparative medicine

2023 Volume 73, Issue 4, Page(s) 285–293

Abstract: Immunodeficient mice engrafted with psoriatic human skin are widely used for the preclinical evaluation of new drug candidates. However, the T-cell activity, including the IL23/IL17 pathway, declines in the graft over time after engraftment, which likely ...

Abstract	Immunodeficient mice engrafted with psoriatic human skin are widely used for the preclinical evaluation of new drug candidates. However, the T-cell activity, including the IL23/IL17 pathway, declines in the graft over time after engraftment, which likely affects the study data. Here, we investigated whether the T-cell activity could be sustained in xenografted psoriatic skin by local stimulation of T cells or systemic injection of autologous CD4 + T cells. We surgically transplanted human psoriatic skin from 5 untreated patients onto female NOG mice. Six days after surgery, mice received an intraperitoneal injection of autologous human CD4
MeSH term(s)	Humans ; Mice ; Female ; Animals ; T-Lymphocytes ; Heterografts ; Skin/pathology ; Psoriasis/drug therapy ; Psoriasis/pathology ; CD4-Positive T-Lymphocytes
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2006425-1
ISSN	2769-819X ; 0023-6764 ; 1532-0820
ISSN (online)	2769-819X
ISSN	0023-6764 ; 1532-0820
DOI	10.30802/AALAS-CM-23-000006
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Article ; Online: CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression.

Cai, Huiqiang / Zhang, Bin / Ahrenfeldt, Johanne / Joseph, Justin V / Riedel, Maria / Gao, Zongliang / Thomsen, Sofie K / Christensen, Ditte S / Bak, Rasmus O / Hager, Henrik / Vendelbo, Mikkel H / Gao, Xin / Birkbak, Nicolai / Thomsen, Martin K

Nature communications

2024 Volume 15, Issue 1, Page(s) 2088

Abstract: Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching ... ...

Abstract	Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C. Depleting Odam and Cabs1 in this region prevents metastasis. Notably, the gene expression signatures, resulting from our study, predict progression-free and overall survival and distinguish primary and metastatic human prostate cancer. This study emphasizes positive genetic interactions between classical tumor suppressor genes and epigenetic modulators in metastatic PCa progression, offering insights into potential treatments.
MeSH term(s)	Male ; Humans ; Animals ; Mice ; CRISPR-Cas Systems/genetics ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Transcriptome ; Multigene Family
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46370-0
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Article: Photodynamic therapy is a safe and feasible adjunct to percutaneous drainage of deep tissue abscesses: Results of a first in humans Phase 1 clinical trial.

Baran, Timothy M / Bass, David A / Christensen, Laurie / Longbine, Erica / Favella, Maria D / Foster, Thomas H / Sharma, Ashwani K

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Standard of care for abscess management includes image-guided percutaneous drainage and antibiotics. However, cure rates vary between patients and there is growing concern for antibiotic-resistant bacteria. Photodynamic therapy (PDT), which ... ...

Abstract	Background: Standard of care for abscess management includes image-guided percutaneous drainage and antibiotics. However, cure rates vary between patients and there is growing concern for antibiotic-resistant bacteria. Photodynamic therapy (PDT), which utilizes light-activated dyes to generate cytotoxic reactive species, could complement the standard of care by sterilizing the abscess at time of drainage. Purpose: The goal of this study was to perform a first in humans Phase 1 clinical study evaluating safety and feasibility of PDT with methylene blue (MB) at the time of percutaneous abscess drainage. This was accomplished through an open-label dose escalation study, with duration of light delivery escalated from 5-30 minutes. Materials and methods: We performed MB-PDT in 18 subjects undergoing percutaneous abscess drainage. Following standard of care drainage, 1 mg/mL MB was delivered for 10 minutes. MB was aspirated, and 1% lipid emulsion infused to homogenize light dose at the cavity wall. An optical fiber was advanced to the approximate center of the abscess for 665 nm laser illumination at 20 mW/cm Results: MB-PDT at the time of abscess drainage was safe and feasible in all cases, with no evidence of fat embolism due to lipid emulsion or adverse reaction to MB observed. No study-related adverse or serious adverse events were encountered, and the procedure was well tolerated by all subjects. While the study was not designed or powered to determine efficacy, time to resolution of clinical symptoms was significantly decreased in subjects receiving higher fluences (p=0.028). Additionally, drainage catheter output post-procedure was decreased in subjects receiving higher fluences (ρ=-0.18), although this difference was not significant (p=0.43). Conclusion: MB-PDT is a safe and feasible adjunct to image-guided percutaneous abscess drainage. Clinical measures indicate a dose-dependent response to PDT, motivating future Phase 2 studies evaluating the efficacy of MB-PDT in this patient population.
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.16.23297086
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Article ; Online: Viral evasion of DNA-stimulated innate immune responses.

Christensen, Maria H / Paludan, Søren R

Cellular & molecular immunology

2016 Volume 14, Issue 1, Page(s) 4–13

Abstract: Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has ...

Abstract	Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.
MeSH term(s)	Animals ; DNA/immunology ; Humans ; Immune Evasion/immunology ; Immunity, Innate ; Models, Biological ; Signal Transduction ; Viruses/immunology
Chemical Substances	DNA (9007-49-2)
Keywords	covid19
Language	English
Publishing date	2016-03-14
Publishing country	China
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/cmi.2016.06
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Article ; Online: Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection.

Albarnaz, Jonas D / Kite, Joanne / Oliveira, Marisa / Li, Hanqi / Di, Ying / Christensen, Maria H / Paulo, Joao A / Antrobus, Robin / Gygi, Steven P / Schmidt, Florian I / Huttlin, Edward L / Smith, Geoffrey L / Weekes, Michael P

Nature communications

2023 Volume 14, Issue 1, Page(s) 8134

Abstract: Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral proteins throughout ... ...

Abstract	Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral proteins throughout MVA infection of human fibroblasts and macrophages. >690 human proteins are down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets are not shared with replication-competent vaccinia. Viral intermediate/late gene expression is necessary for MVA antagonism of innate immunity, and suppression of interferon effectors such as ISG20 potentiates virus gene expression. Proteomic changes specific to infection of macrophages indicate modulation of the inflammatory response, including inflammasome activation. Our approach thus provides a global view of the impact of MVA on the human proteome and identifies mechanisms that may underpin its abortive infection. These discoveries will prove vital to design future generations of vaccines.
MeSH term(s)	Humans ; Vaccinia ; Proteome ; Proteomics ; Vaccinia virus/genetics ; Cell Death ; Antiviral Agents
Chemical Substances	Proteome ; Antiviral Agents
Language	English
Publishing date	2023-12-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43299-8
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Article ; Online: Carriers of COL3A1 pathogenic variants in Denmark: Interfamilial variability in severity and outcome of elective surgical procedures.

Sølyst, Sofus / Oksjoki, Riina / Farholt, Stense / Nielsen, Dorte Guldbrand / Christensen, Alex H / Fagerberg, Christina R / Risom, Lotte / Gregersen, Pernille Axél / Christensen, Maria Bejerholm / Rasmussen, Torsten Bloch / Diness, Birgitte Rode

Clinical genetics

2022 Volume 102, Issue 3, Page(s) 191–200

Abstract: The study describes all patients in Denmark with vascular Ehlers-Danlos syndrome (vEDS). Carriers of pathogenic or likely pathogenic COL3A1 variants were retrospectively identified through registries and specialized clinics. Medical records were reviewed ...

Abstract	The study describes all patients in Denmark with vascular Ehlers-Danlos syndrome (vEDS). Carriers of pathogenic or likely pathogenic COL3A1 variants were retrospectively identified through registries and specialized clinics. Medical records were reviewed for vascular- or organ ruptures and invasive procedures performed. Identified families were divided by variant type (null, splice, and missense) and familial phenotypes (severe or attenuated). Families in which at least one carrier has suffered a major event before the age of 30 were classified as severe, whereas families in which at least three carriers had reached the age of 40 without a major event were classified as attenuated. Eighty-seven persons (59 still alive) from 25 families were included with a mean observation time of 44 years. Sixty-seven percent of patients could be subclassified in a familial phenotype. Thirty-one major events were observed. Eleven complications in 172 invasive procedures were recorded. No fatal complications to elective surgery were observed. The type of COL3A1 variant did not reliably predict phenotype, but a pattern of intrafamilial consistency emerged with some families showing an attenuated form of vEDS. Elective medical procedures appear to be safer than previously thought, although data only allow for conclusions regarding individuals from families with the attenuated form of vEDS.
MeSH term(s)	Collagen Type III/genetics ; Denmark/epidemiology ; Ehlers-Danlos Syndrome/genetics ; Elective Surgical Procedures ; Humans ; Retrospective Studies
Chemical Substances	COL3A1 protein, human ; Collagen Type III
Language	English
Publishing date	2022-07-04
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	221209-2
ISSN	1399-0004 ; 0009-9163
ISSN (online)	1399-0004
ISSN	0009-9163
DOI	10.1111/cge.14176
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