Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/ Cxcr7 axis

The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor ¡1) increased migration of stem cells and their fusion with myoblasts in vitro. Importantly, we identified that Sdf-1 caused an increase in the expression of tetraspanin CD9 - adhesion protein involved in myoblasts fusion. In the current study we aimed to uncover the details of molecular mechanism of Sdf-1 action. We focused at the Sdf-1 receptors - Cxcr4 and Cxcr7, as well as signaling pathways induced by these molecules in primary myoblasts, as well as various stem cells - mesenchymal stem cells and embryonic stem cells, i.e. the cells of different migration and myogenic potential. We showed that Sdf-1 altered actin organization via FAK (focal adhesion kinase), Cdc42 (cell division control protein 42), and Rac-1 (Ras- Related C3 Botulinum Toxin Substrate 1). Moreover, we showed that Sdf-1 modified the transcription profile of genes encoding factors engaged in cells adhesion and migration. As the result, cells such as primary myoblasts or embryonic stem cells, became characterized by more effective migration when transplanted into regenerating muscle

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans : joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios

Interprofessionelle Kommunikation in der Primärversorgung - Fördernde und hemmende Aspekte. Ein narratives Review

Neugebauer T, Brzoska P, Wrona KJ, Yilmaz-Aslan Y, Hämel K. Interprofessionelle Kommunikation in der Primärversorgung - Fördernde und hemmende Aspekte. Ein narratives Review. Pflegewissenschaft. 2022;24(4):241-249

Wahrnehmung von interprofessioneller Kommunikation aus Sicht beteiligter Professionen in der Primärversorgung: Ergebnisse eines narrativen Reviews

Neugebauer T, Brzoska P, Wrona KJ, Yilmaz-Aslan Y, Hämel K. Wahrnehmung von interprofessioneller Kommunikation aus Sicht beteiligter Professionen in der Primärversorgung: Ergebnisse eines narrativen Reviews. Presented at the 20. Deutscher Kongress für Versorgungsforschung.Hintergrund und Stand (inter)nationaler Forschung: Multi-/interprofessionelle Zusammenarbeit gewinnt in der Primärversorgung zunehmend an Aufmerksamkeit, um Versorgungskontinuität zu ermöglichen. Grundlage für eine von den Beteiligten wahrgenommene „gute“ Zusammenarbeit ist eine gelingende Kommunikation zwischen den Professionen. Fragestellung und Zielsetzung: Das Ziel der vorliegenden Arbeit bestand darin, die subjektiven Sichtweisen von in der Primärversorgung tätigen Fachkräften auf fördernde und hemmende Faktoren der professionsübergreifenden Kommunikation in der Primärversorgung sowie im Kontakt zu weiteren Versorgungsanbietern zu analysieren. Methode oder Hypothese: In einem explorativen, narrativen Review wurden 19 internationale, qualitative Studien ausgewertet. Dies erfolgte mittels strukturierten Leitfragen, wodurch die Ergebnisse in Wahrnehmungen, Unterschiede in den Wahrnehmungen und die Beeinflussung dieser differenziert wurden. Ergebnisse: Professionen nehmen in der Kollaboration verschiedene Kommunikationsformen wahr. Als besonders positiv sehen sie dabei die Verbindung von formeller und informeller Kommunikation, bei der neben explizit auf die Versorgung bezogene, fachliche Kommunikation auch stark vertrauensbasierte Kommunikation stattfinden kann. Hierbei wird durch die Entwicklung von gemeinsamen Erfahrens- und Vorgehensweisen eine Verbesserung der Beziehungsebene wahrgenommen. Die Erfahrungen der Professionen zeigen, dass diese essenziell für die Versorgung ist. Die Beziehungsebene wird allerdings von Hierarchien zwischen den Gesundheitsprofessionen beeinflusst, was sich in der interprofessionellen Kommunikation widerspiegelt. Nicht ärztliche Professionen teilen dabei die Erfahrung, dass vertraute Kommunikation mit ärztlichen Professionen wegen zu hoher Erwartungen an sie und Frustrationen durch unklare Rollenverteilung weniger häufig stattfindet. Ein aktiver Austausch von für die Versorgung wichtigen Informationen wird daher oft nicht realisiert. Diskussion: Durch die Verbindung von verschiedenen Kommunikationsformen, die Raum für strukturiert-formell und eher spontan-informell ausgerichtete Kommunikation schaffen, können Beziehungen zwischen den Professionen aufgebaut werden, die ihnen den Austausch erleichtern. Daraus resultiert die Chance, unterschiedliches Wissen und Fähigkeiten miteinander zu verknüpfen und auf die Versorgungssituation anzupassen. Die subjektiven Sichtweisen helfen dabei, hemmende Faktoren der interprofessionellen Kommunikation zu überwinden und zukünftigen Herausforderungen in der Gesundheitsversorgung sowie im Umgang zwischen den Professionen zu adressieren. Praktische Implikationen: Ein Schlüssel für gute interprofessionelle Zusammenarbeit liegt in der Auseinandersetzung mit Kommunikation und dem Verständnis für die „andere“ Profession. Diese müssen demnach erfahrbar gemacht und trainiert werden, um Kommunikation zu stärken. Appell für die Praxis (Wissenschaft und/oder Versorgung) in einem Satz: Um die Zusammenarbeit verschiedener Professionen in der Primärversorgung zu fördern und zu stärken, sollte ein starker Fokus auf die Kommunikationsprozesse gelegt werden

Induction of bone marrow-derived cells myogenic identity by their interactions with the satellite cell niche

Abstract Background Skeletal muscle regeneration is possible thanks to unipotent stem cells, which are satellite cells connected to the myofibers. Populations of stem cells other than muscle-specific satellite cells are considered as sources of cells able to support skeletal muscle reconstruction. Among these are bone marrow-derived mesenchymal stem cells (BM-MSCs), which are multipotent, self-renewing stem cells present in the bone marrow stroma. Available data documenting the ability of BM-MSCs to undergo myogenic differentiation are not definitive. In the current work, we aimed to check if the satellite cell niche could impact the ability of bone marrow-derived cells to follow a myogenic program. Methods We established a new in-vitro method for the coculture of bone marrow-derived cells (BMCs) that express CXCR4 (CXCR4+BMCs; the stromal-derived factor-1 (Sdf-1) receptor) with myofibers. Using various tests, we analyzed the myogenic identity of BMCs and their ability to fuse with myoblasts in vitro and in vivo. Results We showed that Sdf-1 treatment increased the number of CXCR4+BMCs able to bind the myofiber and occupy the satellite cell niche. Moreover, interaction with myofibers induced the expression of myogenic regulatory factors (MRFs) in CXCR4+BMCs. CXCR4+BMCs, pretreated by the coculture with myofibers and Sdf-1, participated in myotube formation in vitro and also myofiber reconstruction in vivo. We also showed that Sdf-1 overexpression in vivo (in injured and regenerating muscles) supported the participation of CXCR4+BMCs in new myofiber formation. Conclusion We showed that CXCR4+BMC interaction with myofibers (that is, within the satellite cell niche) induced CXCR4+BMC myogenic commitment. CXCR4+BMCs, pretreated using such a method of culture, were able to participate in skeletal muscle regeneration

Transient vasodilation in mouse 4T1 tumors after intragastric and intravenous administration of gold nanoparticles

Gold nanoparticles (AuNPs) are foreseen as a promising tool in nanomedicine, both as drug carriers and radiosensitizers. They have been also proposed as a potential anticancer drug due to the anti-angiogenic effect in tumor tissue. In this work we investigated the effect of citrate-coated AuNPs of nominal diameter 20 nm on the growth and metastatic potential of 4T1 cells originated from a mouse mammary gland tumor inoculated into the mammary fat pad of Balb/ccmdb mice. To evaluate whether AuNPs can prevent the tumor growth, one group of inoculated mice was intragastrically (i.g.) administered with 1 mg/kg of AuNPs daily from day 1 to day 14 after cancer cell implantation. To evaluate whether AuNPs can attenuate the tumor growth, the second group was intravenously (i.v.) administered with 1 or 5 mg/kg of AuNPs, twice on day 5 and day 14 after inoculation. We did not observe any anticancer activity of i.v. nor i.g. administered AuNPs, as they did not affect neither the primary tumor growth rate nor the number of lung metastases. Unexpectedly, both AuNP treatment regimens caused a marked vasodilating effect in the tumor tissue. As no change of potential angiogenic genes (Fgf2, Vegfa) nor inducible nitric oxygenase (Nos2) was observed, we proposed that the vasodilation was caused by AuNP-dependent decomposition of nitrosothiols and direct release of nitric oxide in the tumor tissue

Cu,Zn-superoxide dismutase deficiency in mice leads to organ-specific increase in oxidatively damaged DNA and NF-κB1 protein activity

Earlier experimental studies have demonstrated that: i) Cu,Zn-superoxide dismutase deficiency leads to oxidative stress and carcinogenesis; ii) dysregulation of NF-κB pathway can mediate a wide variety of diseases, including cancer. Therefore, we decided, for the first time, to examine the level of oxidative DNA damage and the DNA binding activity of NF-κB proteins in SOD1 knockout, heterozygous and wild-type mice. Two kinds of biomarkers of oxidatively damaged DNA: urinary excretion of 8-oxodG and 8-oxoGua, and the level of oxidatively damaged DNA were analysed using HPLC-GC-MS and HPLC-EC. The DNA binding activity of p50 and p65 proteins in a nuclear extracts was assessed using NF-κB p50/p65 EZ-TFA transcription factor assay. These parameters were determined in the brain, liver, kidney and urine of SOD1 knockout, heterozygous and wild-type mice. The level of 8-oxodG in DNA was higher in the liver and kidney of knockout mice than in wild type. No differences were found in urinary excretion of 8-oxoGua and 8-oxodG between wild type and the SOD1-deficient animals. The activity of the p50 protein was higher in the kidneys, but surprisingly not in the livers of SOD1-deficient mice, whereas p65 activity did not show any variability. Our results indicate that in Cu,Zn-SOD-deficient animals the level of oxidative DNA damage and NF-κB1 activity are elevated in certain organs only, which may provide some explanation for organ-specific ROS-induced carcinogenesis

SDF-1 and NOTCH signaling in myogenic cell differentiation: the role of miRNA10a, 425, and 5100

Abstract Background Skeletal muscle regeneration is a complex process regulated by many cytokines and growth factors. Among the important signaling pathways regulating the myogenic cell identity are these involving SDF-1 and NOTCH. SDF-1 participates in cell mobilization and acts as an important chemoattractant. NOTCH, on the other hand, controls cell activation and myogenic determination of satellite cells. Knowledge about the interaction between SDF-1 and NOTCH signaling is limited. Methods We analyzed two populations of myogenic cells isolated from mouse skeletal muscle, that is, myoblasts derived from satellite cells (SCs) and muscle interstitial progenitor cells (MIPCs). First, microRNA level changes in response to SDF-1 treatment were analyzed with next-generation sequencing (NGS). Second, myogenic cells, i.e., SC-derived myoblasts and MIPCs were transfected with miRNA mimics, selected on the basis of NGS results, or their inhibitors. Transcriptional changes, as well as proliferation, migration, and differentiation abilities of SC-derived myoblasts and MIPCs, were analyzed in vitro. Naive myogenic potential was assessed in vivo, using subcutaneous engrafts and analysis of cell contribution to regeneration of the skeletal muscles. Results SDF-1 treatment led to down-regulation of miR10a, miR151, miR425, and miR5100 in myoblasts. Interestingly, miR10a, miR425, and miR5100 regulated the expression of factors involved in the NOTCH signaling pathway, including Dll1, Jag2, and NICD. Furthermore, miR10a, miR425, and miR5100 down-regulated the expression of factors involved in cell migration: Acta1, MMP12, and FAK, myogenic differentiation: Pax7, Myf5, Myod, Mef2c, Myog, Musk, and Myh3. However, these changes did not significantly affect myogenic cell migration or fusion either in vitro or in vivo, except when miR425 was overexpressed, or miR5100 inhibitor was used. These two molecules increased the fusion of MIPCs and myoblasts, respectively. Furthermore, miR425-transfected MIPC transplantation into injured skeletal muscle resulted in more efficient regeneration, compared to control cell transplantation. However, skeletal muscles that were injected with miR10a transfected myoblasts regenerated less efficiently. Conclusions SDF-1 down-regulates miR10a, miR425, and miR5100, what could affect NOTCH signaling, differentiation of myogenic cells, and their participation in skeletal muscle regeneration