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A new mouse model of radiation-induced liver disease reveals mitochondrial dysfunction as an underlying fibrotic stimulus

Melin, Nicolas ; Yarahmadov, Tural ; Sanchez-Taltavull, Daniel ; [et al.]

Elsevier BV ; 2022

In: JHEP Reports Vol. 4, No. 7 ( 2022-07), p. 100508-

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In: JHEP Reports, Elsevier BV, Vol. 4, No. 7 ( 2022-07), p. 100508-

Type of Medium: Online Resource

ISSN: 2589-5559

URL: Article

DOI: 10.1016/j.jhepr.2022.100508

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2972660-8

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Synergistic effect of the TLR5 agonist CBLB502 and its downstream effector IL-22 against liver injury

Melin, Nicolas ; Sánchez-Taltavull, Daniel ; Fahrner, René ; [et al.]

Springer Science and Business Media LLC ; 2021

In: Cell Death & Disease Vol. 12, No. 4 ( 2021-04-06)

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In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 12, No. 4 ( 2021-04-06)

Abstract: The toll-like receptor 5 (TLR5) agonist, CBLB502/Entolimod, is a peptide derived from bacterial flagellin and has been shown to protect against radiation-induced tissue damage in animal models. Here we investigated the protective mechanism of CBLB502 in the liver using models of ischemia-reperfusion injury and concanavalin A (ConA) induced immuno-hepatitis. We report that pretreatment of mice with CBLB502 provoked a concomitant activation of NF-κB and STAT3 signaling in the liver and reduced hepatic damage in both models. To understand the underlying mechanism, we screened for cytokines in the serum of CBLB502 treated animals and detected high levels of IL-22. There was no transcriptional upregulation of IL-22 in the liver, rather it was found in extrahepatic tissues, mainly the colon, mesenteric lymph nodes (MLN), and spleen. RNA-seq analysis on isolated hepatocytes demonstrated that the concomitant activation of NF-κB signaling by CBLB502 and STAT3 signaling by IL-22 produced a synergistic cytoprotective transcriptional signature. In IL-22 knockout mice, the loss of IL-22 resulted in a decrease of hepatic STAT3 activation, a reduction in the cytoprotective signature, and a loss of hepatoprotection following ischemia-reperfusion-induced liver injury. Taken together, these findings suggest that CBLB502 protects the liver by increasing hepatocyte resistance to acute liver injury through the cooperation of TLR5-NF-κB and IL-22-STAT3 signaling pathways.

Type of Medium: Online Resource

ISSN: 2041-4889

URL: Article

DOI: 10.1038/s41419-021-03654-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2541626-1

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ILC3s restrict the dissemination of intestinal bacteria to safeguard liver regeneration after surgery

Jakob, Manuel O. ; Spari, Daniel ; Sànchez Taltavull, Daniel ; [et al.]

Elsevier BV ; 2023

In: Cell Reports Vol. 42, No. 3 ( 2023-03), p. 112269-

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In: Cell Reports, Elsevier BV, Vol. 42, No. 3 ( 2023-03), p. 112269-

Type of Medium: Online Resource

ISSN: 2211-1247

URL: Article

DOI: 10.1016/j.celrep.2023.112269

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2649101-1

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Is it really advantageous to operate proximal femoral fractures within 48 h from diagnosis? – A multicentric retrospective study exploiting COVID pandemic-related delays in time to surgery

Giacomo, Placella ; Bettinelli, Giulia ; Alberto, Iacomella ; [et al.]

Scientific Scholar ; 2022

In: Journal of Musculoskeletal Surgery and Research Vol. 6 ( 2022-05-21), p. 154-159

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In: Journal of Musculoskeletal Surgery and Research, Scientific Scholar, Vol. 6 ( 2022-05-21), p. 154-159

Abstract: Hip fractures in the elderly are common injuries that need timely surgical management. Since the beginning of the pandemic, patients with a proximal femoral fracture (PFF) experienced a delay in time to surgery. The primary aim of this study was to evaluate a possible variation in mortality in patients with PFF when comparing COVID-19 negative versus positive. Methods: This is a multicentric and retrospective study including 3232 patients with PFF who underwent surgical management. The variables taken into account were age, gender, the time elapsed between arrival at the emergency room and intervention, pre-operative American Society of Anesthesiology score, pre-operative cardiovascular and respiratory disease, and 10-day/1-month/6-month mortality. For 2020, we had an additional column, “COVID-19 swab positivity.” Results: COVID-19 infection represents an independent mortality risk factor in patients with PFFs. Despite the delay in time-to-surgery occurring in 2020, no statistically significant variation in terms of mortality was detected. Within our sample, a statistically significant difference was not detected in terms of mortality at 6 months, in patients operated within and beyond 48 h, as well as no difference between those operated within or after 12/24/72 h. The mortality rate among subjects with PFF who tested positive for COVID-19 was statistically significantly higher than in patients with PFF who tested. COVID-19 positivity resulted in an independent factor for mortality after PFF. Conclusion: Despite the most recent literature recommending operating PFF patients as soon as possible, no significant difference in mortality was found among patients operated before or after 48 h from diagnosis.

Type of Medium: Online Resource

ISSN: 2589-1227 , 2589-1219

URL: Journal

URL: Article

DOI: 10.25259/JMSR

DOI: 10.25259/JMSR_36_2022

Language: English

Publisher: Scientific Scholar

Publication Date: 2022

detail.hit.zdb_id: 3043230-3

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Macrophage regulation of PKM2 during liver regeneration process

Melin, Nicolas ; Joel, Zindel ; Loforese, Giulio ; [et al.]

Elsevier BV ; 2020

In: Journal of Hepatology Vol. 73 ( 2020-08), p. S246-S247

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In: Journal of Hepatology, Elsevier BV, Vol. 73 ( 2020-08), p. S246-S247

Type of Medium: Online Resource

ISSN: 0168-8278

URL: Article

DOI: 10.1016/S0168-8278(20)30997-1

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2027112-8

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The LIM Protein Ajuba Augments Tumor Metastasis in Colon Cancer

Dommann, Noëlle ; Sánchez-Taltavull, Daniel ; Eggs, Linda ; [et al.]

MDPI AG ; 2020

In: Cancers Vol. 12, No. 7 ( 2020-07-15), p. 1913-

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In: Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-07-15), p. 1913-

Abstract: Colorectal cancer, along with its high potential for recurrence and metastasis, is a major health burden. Uncovering proteins and pathways required for tumor cell growth is necessary for the development of novel targeted therapies. Ajuba is a member of the LIM domain family of proteins whose expression is positively associated with numerous cancers. Our data shows that Ajuba is highly expressed in human colon cancer tissue and cell lines. Publicly available data from The Cancer Genome Atlas shows a negative correlation between survival and Ajuba expression in patients with colon cancer. To investigate its function, we transduced SW480 human colon cancer cells, with lentiviral constructs to knockdown or overexpress Ajuba protein. The transcriptome of the modified cell lines was analyzed by RNA sequencing. Among the pathways enriched in the differentially expressed genes, were cell proliferation, migration and differentiation. We confirmed our sequencing data with biological assays; cells depleted of Ajuba were less proliferative, more sensitive to irradiation, migrated less and were less efficient in colony formation. In addition, loss of Ajuba expression decreased the tumor burden in a murine model of colorectal metastasis to the liver. Taken together, our data supports that Ajuba promotes colon cancer growth, migration and metastasis and therefore is a potential candidate for targeted therapy.

Type of Medium: Online Resource

ISSN: 2072-6694

URL: Article

DOI: 10.3390/cancers12071913

Language: English

Publisher: MDPI AG

Publication Date: 2020

detail.hit.zdb_id: 2527080-1

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Regular testing of asymptomatic healthcare workers identifies cost-efficient SARS-CoV-2 preventive measures

Sanchez-Taltavull, Daniel ; Castelo-Szekely, Violeta ; Murugan, Shaira ; [et al.]

Public Library of Science (PLoS) ; 2021

In: PLOS ONE Vol. 16, No. 11 ( 2021-11-5), p. e0258700-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 11 ( 2021-11-5), p. e0258700-

Abstract: Protecting healthcare professionals is crucial in maintaining a functioning healthcare system. The risk of infection and optimal preventive strategies for healthcare workers during the COVID-19 pandemic remain poorly understood. Here we report the results of a cohort study that included pre- and asymptomatic healthcare workers. A weekly testing regime has been performed in this cohort since the beginning of the COVID-19 pandemic to identify infected healthcare workers. Based on these observations we have developed a mathematical model of SARS-CoV-2 transmission that integrates the sources of infection from inside and outside the hospital. The data were used to study how regular testing and a desynchronisation protocol are effective in preventing transmission of COVID-19 infection at work, and compared both strategies in terms of workforce availability and cost-effectiveness. We showed that case incidence among healthcare workers is higher than would be explained solely by community infection. Furthermore, while testing and desynchronisation protocols are both effective in preventing nosocomial transmission, regular testing maintains work productivity with implementation costs.

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0258700

DOI: 10.1371/journal.pone.0258700.g001

DOI: 10.1371/journal.pone.0258700.g002

DOI: 10.1371/journal.pone.0258700.g003

DOI: 10.1371/journal.pone.0258700.g004

DOI: 10.1371/journal.pone.0258700.t001

DOI: 10.1371/journal.pone.0258700.t002

DOI: 10.1371/journal.pone.0258700.s001

DOI: 10.1371/journal.pone.0258700.s002

DOI: 10.1371/journal.pone.0258700.s003

DOI: 10.1371/journal.pone.0258700.s004

DOI: 10.1371/journal.pone.0258700.s005

DOI: 10.1371/journal.pone.0258700.s006

DOI: 10.1371/journal.pone.0258700.r001

DOI: 10.1371/journal.pone.0258700.r002

DOI: 10.1371/journal.pone.0258700.r003

DOI: 10.1371/journal.pone.0258700.r004

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2021

detail.hit.zdb_id: 2267670-3

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Dosch, Michel ; Zindel, Joël ; Jebbawi, Fadi ; [et al.]

eLife Sciences Publications, Ltd ; 2019

In: eLife Vol. 8 ( 2019-02-08)

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In: eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-02-08)

Abstract: Bacterial spillage into a sterile environment following intestinal hollow-organ perforation leads to peritonitis and fulminant sepsis. Outcome of sepsis critically depends on macrophage activation by extracellular ATP-release and associated autocrine signalling via purinergic receptors. ATP-release mechanisms, however, are poorly understood. Here, we show that TLR-2 and −4 agonists trigger ATP-release via Connexin-43 hemichannels in macrophages leading to poor sepsis survival. In humans, Connexin-43 was upregulated on macrophages isolated from the peritoneal cavity in patients with peritonitis but not in healthy controls. Using a murine peritonitis/sepsis model, we identified increased Connexin-43 expression in peritoneal and hepatic macrophages. Conditional Lyz2cre/creGja1flox/flox mice were developed to specifically assess Connexin-43 impact in macrophages. Both macrophage-specific Connexin-43 deletion and pharmacological Connexin-43 blockade were associated with reduced cytokine secretion by macrophages in response to LPS and CLP, ultimately resulting in increased survival. In conclusion, inhibition of autocrine Connexin-43-dependent ATP signalling on macrophages improves sepsis outcome.

Type of Medium: Online Resource

ISSN: 2050-084X

URL: Article

DOI: 10.7554/eLife.42670

DOI: 10.7554/eLife.42670.001

DOI: 10.7554/eLife.42670.002

DOI: 10.7554/eLife.42670.003

DOI: 10.7554/eLife.42670.004

DOI: 10.7554/eLife.42670.005

DOI: 10.7554/eLife.42670.006

DOI: 10.7554/eLife.42670.007

DOI: 10.7554/eLife.42670.008

DOI: 10.7554/eLife.42670.009

DOI: 10.7554/eLife.42670.010

DOI: 10.7554/eLife.42670.011

DOI: 10.7554/eLife.42670.012

DOI: 10.7554/eLife.42670.013

DOI: 10.7554/eLife.42670.014

DOI: 10.7554/eLife.42670.015

DOI: 10.7554/eLife.42670.016

DOI: 10.7554/eLife.42670.017

DOI: 10.7554/eLife.42670.018

DOI: 10.7554/eLife.42670.019

DOI: 10.7554/eLife.42670.020

DOI: 10.7554/eLife.42670.022

DOI: 10.7554/eLife.42670.023

Language: English

Publisher: eLife Sciences Publications, Ltd

Publication Date: 2019

detail.hit.zdb_id: 2687154-3

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Primed liver regeneration in protein convertase subtilisin/kexin type 9 knockout mice is associated with increased lipids uptake and hypercholesterolemia

Gavini, Jacopo ; Leuenberger, Dana ; Sanchez-Taltavull, Daniel ; [et al.]

Elsevier BV ; 2020

In: Journal of Hepatology Vol. 73 ( 2020-08), p. S243-S244

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In: Journal of Hepatology, Elsevier BV, Vol. 73 ( 2020-08), p. S243-S244

Type of Medium: Online Resource

ISSN: 0168-8278

URL: Article

DOI: 10.1016/S0168-8278(20)30991-0

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2027112-8

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Optimal liver metabolism and proliferation require the tight junction protein claudin-3

Baier, Felix Alexander ; Sanchez-Taltavull, Daniel ; Jebbawi, Fadi ; [et al.]

Elsevier BV ; 2020

In: Journal of Hepatology Vol. 73 ( 2020-08), p. S245-S246

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In: Journal of Hepatology, Elsevier BV, Vol. 73 ( 2020-08), p. S245-S246

Type of Medium: Online Resource

ISSN: 0168-8278

URL: Article

DOI: 10.1016/S0168-8278(20)30995-8

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2027112-8

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