3 research outputs found
Laurus nobilis (laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice
Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat,
fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed
in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and
hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was
administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental
groups (n = 10) (group I: HPV16−/− without treatment, group II: treated HPV16−/−, group III: HPV16+/−
without treatment and group IV: treated HPV16+/−). Following the treatment period, animals were sacrificed
and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological
and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The
extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wildtype
animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no
changes concerning hematological, biochemical and hepatic oxidative stress markers.This work was supported by: Integrative Research in
Environment, Agro-Chains and Technology no. NORTE-01-
0145-FEDER-000017, in its line of research entitled ISAC, cofinanced
by the European Regional Development Fund (ERDF)
through NORTE 2020 (North Regional Operational Program
2014/2020). European Investment Funds by FEDER/COMPETE/
POCI– Operational Competitiveness and Internationalization
Programme, under Project POCI-01-0145-FEDER-006958 and
National Funds by FCT - Portuguese Foundation for Science
and Technology, under the project UID/AGR/04033/2013. This
study was also funded by Liga Portuguesa Contra o Cancro, by
the Research Center of the Portuguese Institute of Oncology of
Porto (CI-IPOP 37-2016), by project POCI-01-0145-
FEDER-006939 (Laboratory for Process Engineering,
Environment, Biotechnology and Energy – LEPABE), project
POCI-01-0145-FEDER-006958 and UID/AGR/04033/2013,
funded by FEDER funds through COMPETE2020 - Programa
Operacional Competitividade e Internacionalização (POCI) –
and by national funds through FCT – Fundação para a Ciência
e a Tecnologia; Rui M. Gil da Costa was funded by grant
number SFRH/BPD/85462/2012 from FCT, funded by the
Portuguese Government and the Social European Fund. The
authors are also grateful to FCT, Portugal and FEDER under
Programme PT2020 for financial support to CIMO (UID/AGR/
00690/2013), and to the Interreg España-Portugal for financial
support through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio
Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates
International audienceNo curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery. In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. Methods: The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia. We orally administrated GW2580, a CSF1R inhibitor that inhibits microglia proliferation. In mice and nonhuman primates, we then analyzed treatment outcomes on locomotor function and spinal cord pathology. Finally, we used cell-specific transcriptomic analysis to uncover GW2580-induced molecular changes in microglia. Results: First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissue preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity. Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves motor function recovery, and promotes tissue protection. Finally, GW2580-treatment in mice induced down-regulation of proliferation-associated transcripts and inflammatory associated genes in microglia that may account for reduced neuroinflammation and improved functional recovery following SCI. Conclusion: Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation
Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates
Abstract No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery. In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor. First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity. Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value. Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment. Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation