A new family of luminescent [Pt(pbt)(CF)L] ( = 1, 0) complexes: synthesis, optical and cytotoxic studies.

Given the widely recognized bioactivity of 2-arylbenzothiazoles against tumor cells, we have designed a new family of luminescent heteroleptic pentafluorophenyl-bis(2-phenylbenzothiazolyl) Pt derivatives, -[Pt(pbt)(CF)L] ( = 1, 0) [L = 4-Mepy 1, 4-pyridylbenzothiazole (pybt) 2, 4,4'-bipyridine (4,4'-bpy) 3, 1,2-bis-(4-pyridyl)ethylene (bpe) 4 (/ ratio: 90/10), 1,4-bis-(pyridyl)butadiyne (bpyb) 5, trifluoroacetate (OCOCF) 6] and a dinuclear complex [{Pt(pbt)(CF)}(μ-bpyb)](PF)7, in which the ligand to the metalated C-(pbt) was varied to modify the optical properties and lipophilicity. Their photophysical properties were systematically studied through experimental and theoretical investigations, which were strongly dependent on the identity of the N-bonded ligand. Thus, complexes 1, 3 and 6 display, in different media, emission from the triplet excited states of primarily intraligand ILCT nature localized on the pbt ligand, while the emissions of 2, 5 and 7 were ascribed to a mixture of close IL'(N donor)/ILCT(pbt) excited states, as supported by lifetime measurements and theoretical calculations.

Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer.

Recent studies highlight the importance of baseline functional immunity for immune checkpoint blockade therapies. High-dimensional systemic immune profiling is performed in a cohort of non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders show high baseline myeloid phenotypic diversity in peripheral blood.

A new family of luminescent iridium complexes: synthesis, optical, and cytotoxic studies.

By using ,-dibutyl-2,2'-bipyridine-4,4'-dicarboxamide as a diimine () and distinctive cyclometalated groups, this work reports a new family of cationic phosphorescent Ir(III) cyclometalated [Ir(C^N)(N^N)]X compounds [C^N = difluorophenylpyridine (dfppy) a, 2,6-difluoro-3-(pyridin-2-yl)benzaldehyde (CHO-dfppy) b, and 2,6-difluoro-3-pyridin-2-yl-benzoic acid (COOH-dfppy) c; X = Cl2a,b,c-Cl; X = PF2b,c-PF6]. For comparative purposes, the related complex [Ir(dfppy)(Hdcbpy)] (3a-PF6) incorporating 3,3'-dicarboxy-2,2'-bipyridine as an auxiliary ligand (N^N = Hdcbpy) is also presented. All complexes have been fully characterized and their photophysical properties were investigated in detail.

IGF1R is a mediator of sex-specific metabolism in mice: Effects of age and high-fat diet.

Objective: We aimed to investigate the short and long-term metabolic consequences of IGF1R systemic gene deficiency in mice.

Methods: mutant mice were used to suppress IGF1R signaling in adult tissues by inducing postnatal generalized deletion with tamoxifen. Animals were analyzed at two different ages: ) 13-weeks old young mice, and ) 12-months old middle-aged mice.

IGF1R acts as a cancer-promoting factor in the tumor microenvironment facilitating lung metastasis implantation and progression.

Given the long-term ineffectiveness of current therapies and late-stage diagnoses, lung cancer is a leading cause of malignant diseases. Tumor progression is influenced by cancer cell interactions with the tumor microenvironment (TME). Insulin-like growth factor 1 receptor (IGF1R) was reported to affect the TME; however, the role of IGF1R in lung TME has not been investigated.

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

In the original article [...

IGF1R as a Potential Pharmacological Target in Allergic Asthma.

Background: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma.

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 N-pbt)(C F )}L] [L=Me N-pbtH 1, p-dpbH (4-(diphenylphosphino)benzoic acid) 2, o-dpbH (2-(diphenylphosphino)benzoic acid) 3), [Pt(Me N-pbt)(o-dpb)] 4, [{Pt(Me N-pbt)(C F )} (μ-PR P)] [PR P=O(CH CH OC(O)C H PPh ) 5, PR P=O{(CH CH O) C(O)C H PPh } 6] are presented. Complexes 1-6 display ILCT and metal-perturbed ILCT dual emissions. The ratio between both bands is excitation dependent, accomplishing warm-white emissions for 2, 5 and 6.

Luminescent cyclometalated platinum(ii) complexes with acyclic diaminocarbene ligands: structural, photophysical and biological properties.

Four new cyclometalated Pt(ii) complexes bearing acyclic diaminocarbene (ADC) ligands, [Pt(C^N)Cl{C(NHXyl)(NHR)}] [C^N = 2,6-difluorophenylpyridine (dfppy), phenylquinoline (pq); R = Pr 3a, 4a, CHPh 3b, 4b], were prepared by the nucleophilic attack on the isocyanide [Pt(C^N)Cl(CNXyl)] (C^N = dfppy 1, pq 2) by the corresponding amine RNH (R = Pr, CHPh). Complexes 3 show in their H NMR spectra in CDCl a notable concentration dependence, with a clear variation of the δ (NHXyl) signal, suggesting an assembling process implying donor-acceptor NHCl bonding, also supported by 1D-PGSE (Pulse Field Gradient Spin Echo) and 2D-DOSY (Diffusion Ordered Spectroscopy) NMR experiments in solution and X-ray diffraction studies. The intermolecular interactions in compounds 3a and 3b were studied by using Hirshfeld surface analysis and Non-Covalent Interaction (NCI) methods on their X-ray structures.

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 ; male mice in which was conditionally deleted.

Cigarette Smoke Directly Promotes Pulmonary Arterial Remodeling and Kv7.4 Channel Dysfunction.

Cigarette smoke is considered the chief leading cause of chronic obstructive pulmonary disease (COPD). Its impact on the progressive deterioration of airways has been extensively studied, but its direct effects on the pulmonary vasculature are less known. To prove that pulmonary arterial remodeling in patients with COPD is not just a consequence of alveolar hypoxia but also due to the direct effects of cigarette smoke on the pulmonary vascular bed.

Luminescent Cycloplatinated Complexes with Biologically Relevant Phosphine Ligands: Optical and Cytotoxic Properties.

Two series of neutral luminescent pentafluorophenyl cycloplatinated(II) complexes [Pt(C^N)(CF)L] [C^N = C-deprotonated 2-phenylpyridine (ppy; a), 2-(2,4-difluorophenylpyridine (dfppy; b)] incorporating dimethyl sulfoxide [L = DMSO for 1 (1a reported by us in ref (14) )] or biocompatible phosphine [L = PPhCHCOOH (dpbH; 2), PPhCHCONHCHCOOMe (dpbGlyOMe; 3), P(CHSONa) (TPPTS; 4)] ligands have been prepared and characterized and their optical properties studied. Their cytotoxic activities against tumor A549 (lung carcinoma), HeLa (cervix carcinoma), and nontumor NL-20 (lung epithelium) cell lines, as well as the ability to interact with DNA (plasmid pBR322), were evaluated. Complexes 2 exhibit higher cytotoxicity (IC 3.

Prominent release of lipoxygenase generated mediators in a murine house dust mite-induced asthma model.

The profile of activation of lipid mediator (LM) pathways in asthmatic airway inflammation remains unclear. This experimental study quantified metabolite levels of ω3-, ω6- and ω9-derived polyunsaturated fatty acids in bronchoalveolar lavage fluid (BALF) after 4-weeks of repeated house dust mite (HDM) exposure in a murine (C57BL/6) asthma model. The challenge induced airway hyperresponsiveness, pulmonary eosinophil infiltration, but with low and unchanged mast cell numbers.

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.

Benzothiazole-Based Cycloplatinated Chromophores: Synthetic, Optical, and Biological Studies.

Cycloplatinated complexes based on 2-(4-substituted)benzothiazole ligands of type [Pt(R-PBT-κC,N)Cl(L)] (PBT=2-phenylbenzothiazole; R=Br (1), Me N (2); L=dimethyl sulfoxide (DMSO; a), 1,3,5- triaza-7-phosphaadamantane (PTA; b), triphenylphosphine 3,3',3''-trisulfonate (TPPTS; c)) and [Pt(Br-PBT-κC)Cl(PTA) ] (3) are presented. On the basis of the photophysical data and time-dependent (TD)-DFT calculations (1 a and 2 a), the low-lying transitions (absorption and emission) were associated with ligand-center (LC) charge transfer, with minor metal-to-ligand charge transfer (MLCT), and intraligand charge transfer (ILCT) [Me N-PBT→PBT] excited states, respectively. Simultaneous fluorescence/phosphorescence bands were found in fluid solutions (and also in the solid state for 2 a), which become dominated by triplet emission bands in rigid media at 77 K.

IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model.

IGF1R (Insulin-like Growth Factor 1 Receptor) is a tyrosine kinase with pleiotropic cellular functions. IGF activity maintains human lung homeostasis and is implicated in pulmonary diseases such as cancer, ARDS, COPD, asthma and fibrosis. Here we report that lung transcriptome analysis in mice with a postnatally-induced Igf1r gene deletion showed differentially expressed genes with potentially protective roles related to epigenetics, redox and oxidative stress.

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

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.

Maraviroc ameliorates the increased adipose tissue macrophage recruitment induced by a high-fat diet in a mouse model of obesity.

Background: Any strategy designed to decrease the macrophage content in adipose tissue (AT) is of great value as a way to decrease inflammation in this fat depot and also as a way to prevent or treat obesity and associated disorders. Maraviroc (MVC), a CCR5 antagonist approved for the treatment of HIV-infected patients, has beneficial effects on metabolism. The objective of this study was to investigate the effects of MVC on AT macrophage recruitment in a mouse model of obesity.

Differential organ phenotypes after postnatal Igf1r gene conditional deletion induced by tamoxifen in UBC-CreERT2; Igf1r fl/fl double transgenic mice.

Insulin-like growth factor type 1 receptor (IGF1R) is a ubiquitously expressed tyrosine kinase that regulates cell proliferation, differentiation and survival. It controls body growth and organ homeostasis, but with specific functions depending on developmental time and cell type. Human deficiency in IGF1R is involved in growth failure, microcephaly, mental retardation and deafness, and its overactivation is implicated in oncogenesis.

Transcriptome analysis in prenatal IGF1-deficient mice identifies molecular pathways and target genes involved in distal lung differentiation.

Background: Insulin-like Growth Factor 1 (IGF1) is a multifunctional regulator of somatic growth and development throughout evolution. IGF1 signaling through IGF type 1 receptor (IGF1R) controls cell proliferation, survival and differentiation in multiple cell types. IGF1 deficiency in mice disrupts lung morphogenesis, causing altered prenatal pulmonary alveologenesis.

RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors.

Background: Insulin-like growth factor-I (IGF-I) provides pivotal cell survival and differentiation signals during inner ear development throughout evolution. Homozygous mutations of human IGF1 cause syndromic sensorineural deafness, decreased intrauterine and postnatal growth rates, and mental retardation. In the mouse, deficits in IGF-I result in profound hearing loss associated with reduced survival, differentiation and maturation of auditory neurons.

Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF-I double deficient embryos.

Previous studies on double deficient mice for leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) reported that they died of respiratory failure, with abnormal lung histology and altered expression of pulmonary markers. Here we analyzed prenatal Lif/Igf-I double mutant mouse embryos to characterize LIF and IGF-I cooperative roles in distal lung epithelium and vascular maturation. Lungs of IGF-I-deficient embryos displayed a higher proportion of type II pneumocytes, less differentiated type I pneumocytes, and failure in alveolar capillary remodeling compared to wild type and LIF-deficient mice.

Mice lacking IGF-I and LIF have motoneuron deficits in brain stem nuclei.

We analyzed the neural embryonic phenotype of single and double-mutant mice for insulin-like growth factor-I (IGF-I) and leukemia inhibitory factor (LIF). The anatomical structure of the hippocampus, the cerebellum, and the olfactory epithelium, regions showing expression of both factors and their receptors, appeared largely normal in all mutant mice. In the fimbria and the spinal cord, similar patterns of glial fibrillary acidic protein (GFAP)-expressing astrocytes were found in wild-type and mutant mice.