Correction: Alfaro-Arnedo et al. IGF1R as a Potential Pharmacological Target in Allergic Asthma. Biomedicines 2021, 9, 912

Correction to Biomedicines 2021, 9(8), 912.Depto. de FisiologíaFac. de MedicinaTRUEpu

IGF1R Deficiency Modulates Brain Signaling Pathways and Disturbs Mitochondria and Redox Homeostasis

Insulin-like growth factor 1 receptor (IGF1R)-mediated signaling pathways modulate important neurophysiological aspects in the central nervous system, including neurogenesis, synaptic plasticity and complex cognitive functions. In the present study, we intended to characterize the impact of IGF1R deficiency in the brain, focusing on PI3K/Akt and MAPK/ERK1/2 signaling pathways and mitochondria-related parameters. For this purpose, we used 13-week-old UBC-CreERT2; Igf1rfl/fl male mice in which Igf1r was conditionally deleted. IGF1R deficiency caused a decrease in brain weight as well as the activation of the IR/PI3K/Akt and inhibition of the MAPK/ERK1/2/CREB signaling pathways. Despite no alterations in the activity of caspases 3 and 9, a significant alteration in phosphorylated GSK3β and an increase in phosphorylated Tau protein levels were observed. In addition, significant disturbances in mitochondrial dynamics and content and altered activity of the mitochondrial respiratory chain complexes were noticed. An increase in oxidative stress, characterized by decreased nuclear factor E2-related factor 2 (NRF2) protein levels and aconitase activity and increased H2O2 levels were also found in the brain of IGF1R-deficient mice. Overall, our observations confirm the complexity of IGF1R in mediating brain signaling responses and suggest that its deficiency negatively impacts brain cells homeostasis and survival by affecting mitochondria and redox homeostasis

Investigation on Optical and Biological Properties of 2-(4-Dimethylaminophenyl)benzothiazole Based Cycloplatinated Complexes

The optical and biological properties of 2‐(4‐dimethylaminophenyl)benzothiazole cycloplatinated complexes featuring bioactive ligands ([{Pt(Me(2)N‐pbt)(C(6)F(5))}L] [L=Me(2)N‐pbtH 1, p‐dpbH (4‐(diphenylphosphino)benzoic acid) 2, o‐dpbH (2‐(diphenylphosphino)benzoic acid) 3), [Pt(Me(2)N‐pbt)(o‐dpb)] 4, [{Pt(Me(2)N‐pbt)(C(6)F(5))}(2)(μ‐PR( n )P)] [PR(4)P=O(CH(2)CH(2)OC(O)C(6)H(4)PPh(2))(2) 5, PR(12)P=O{(CH(2)CH(2)O)(3)C(O)C(6)H(4)PPh(2)}(2) 6] are presented. Complexes 1–6 display (1)ILCT and metal‐perturbed (3)ILCT dual emissions. The ratio between both bands is excitation dependent, accomplishing warm‐white emissions for 2, 5 and 6. The phosphorescent emission is lost in aerated solutions owing to photoinduced electron transfer to (3)O(2) and the formation of (1)O(2), as confirmed in complexes 2 and 4. They also exhibit photoinduced phosphorescence enhancement in non‐degassed DMSO due to local oxidation of DMSO by sensitized (1)O(2), which causes a local degassing. Me(2)N‐pbtH and the complexes specifically accumulate in the Golgi apparatus, although only 2, 3 and 6 were active against A549 and HeLa cancer cell lines, 6 being highly selective in respect to nontumoral cells. The potential photodynamic property of these complexes was demonstrated with complex 4

Correction: Alfaro-Arnedo et al. IGF1R as a Potential Pharmacological Target in Allergic Asthma. Biomedicines 2021, 9, 912

In the original article [...

Characterization of the acute inflammatory profile and resolution of airway inflammation after Igf1r-gene targeting in a murine model of HDM-induced asthma.

Asthma is a chronic inflammatory disease characterized by bronchial hyperresponsiveness, mucus overproduction and airway remodeling. Notably, we have recently demonstrated that insulin-like growth factor 1 receptor (IGF1R) deficiency in mice attenuates airway hyperresponsiveness and mucus secretion after chronic house dust mite (HDM) exposure. On this basis, inbred C57BL/6 and Igf1r-deficient mice were given HDM extract to study the acute inflammatory profile and implication of Igf1r in acute asthma pathobiology. Additionally, Igf1r-deficiency was therapeutically induced in mice to evaluate the resolution of HDM-induced inflammation. Acute HDM exposure in inbred C57BL/6 mice led to a progressive increase in inflammation, airway remodeling and associated molecular indicators. Preventively-induced Igf1r-deficiency showed reduced neutrophil and eosinophil numbers in BALF and bone marrow, a significant reduction of airway remodeling and decreased levels of related markers. In addition, therapeutic targeting of Igf1r promoted the resolution of HDM-induced-inflammation. Our results demonstrate for the first time that Igf1r is important in acute asthma pathobiology and resolution of HDM-induced inflammation. Thus, IGF1R is suggested to be a promising candidate for future therapeutic approaches for the treatment and prevention of asthma

Involvement of Igf1r in Bronchiolar Epithelial Regeneration: Role during Repair Kinetics after Selective Club Cell Ablation

<div><p>Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific <i>Igf1r</i> mutant mice were generated and studied. The lack of <i>Igf1r</i> disturbed airway epithelial differentiation in adult mice, and revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in <i>Igf1r</i> mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of <i>Igf1r</i> deficient mice showed increased levels of <i>Igf1</i>, <i>Insr</i>, <i>Igfbp3</i> and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury.</p></div

Cytolocalyzation and cytotoxicity of new luminescent cyclometalated platinum(II) complexes: use as organelle biomarkers and antitumoral drugs with potential in photodynamic therapy

Two series of luminescent cyclometalated Pt(II) com-plexes were synthesized a nd their biological activitywas assessed. One was based on the deprotonated do-nor-acceptor 2-(4-dimethylaminephenyl)benzothiazoleligand (NMe 2 -pbt) and includes four mononuclear com-plexes [Pt(Me2N-pbt)(C6F5 )L] (L = Me2N-pbtH) 1, p-dpbH(4-diphenylphosphino)benzoic acid) 2, o-dpbH (2-diphe-nylphosphino)benzoic acid) [Pt(Me2N-pbt)(C6F5 )(o-dpbH)]3 (unstable), and [Pt(Me2N-pbt)(o-dpb)] 4, as well as oftwo binuclear derivatives [{Pt(Me2N-pbt)(C6F5 )}2(m-PRnP)][PR4 P = O(CH2CH2OC(O)C6H 4PPh 2)2 5; PR12P = O{(CH-2CH2O)3C(O)C6H 4PPh 2}2 6]. The second includes 2,6-di-fluorophenylpyridine (dfppy) and phenylquinoline (pq) aschromophores and acyclic diaminocarbene (ADC) ligandsas auxiliary ligands [Pt(C^N)Cl{C(NHXyl)(NHR)}] [C^N =dfppy (a), pq (b); R = Pr 7a, 8a, CH2 Ph 7b, 8b]. In theNMe2-pbt based complexes the phosphorescent emissionis lost in aerated solutions, owing to photoinduced electrontransfer to 3 O2 and formation 1 O2 singlet, as confirmed incomplexes 2 and 4. Here we report some of their biological activity. Cytotoxicity studies in the human cancer celllines A549 (lung carcinoma) and HeLa (cervix carcinoma)showed good activity for the ADC complexes 7 and 8. Tothe best of our knowledge, these compounds representthe first examples of cycloplatinated complexes bearingacyclic diamino carbenes with antiproliferative properties(Ref.). Accordingly, 7a, 7b and 8a altered DNA electropho-retic mobility pointing as a possible cytotoxic mechanism.NMe2-pbt complexes 2, 3 and 6 were also active againstA549 and HeLa cancer cells, with higher efficiency in A549,in contrast to 1, 4, and 5. Cytolocalization studies revealedthat the no cytotoxic ligand Me 2 N-pbtH and their deriva-tive complexes 1-6 exhibit specific accumulation in theGolgi apparatus. Furthermore, the potential photodynamicproperty of this type of complexes was demonstrated withthe non-cytotoxic complex 4, which demonstrated efficientphotoinduced cytotoxicity after irradiation