Expression of Mitochondrial Long Non-Coding RNAs, MDL1 and MDL1AS, Are Good Prognostic and/or Diagnostic Biomarkers for Several Cancers, Including Colorectal Cancer.

Non-coding RNAs provide new opportunities to identify biomarkers that properly classify cancer patients. Here, we study the biomarker status of the mitochondrial long non-coding RNAs, MDL1 and MDL1AS. Expression of these genes was studied in public transcriptomic databases.

MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study.

Background And Purpose: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications.

Targeting 7KCh-Induced Cell Death Response Mediated by p38, P2X7 and GSDME in Retinal Pigment Epithelium Cells with Sterculic Acid.

Age-related macular degeneration (AMD) is the main cause of blindness in developed countries. AMD is characterized by the formation of drusen, which are lipidic deposits, between retinal pigment epithelium (RPE) and the choroid. One of the main molecules accumulated in drusen is 7-Ketocholesterol (7KCh), an oxidized-cholesterol derivative.

A hypothermia mimetic molecule (zr17-2) reduces ganglion cell death, gliosis, and electroretinogram distortion in male rats subjected to perinatal asphyxia.

Perinatal asphyxia (PA) represents a major problem in perinatology and may cause visual losses, including blindness. We, and others, have shown that hypothermia prevents retinal symptoms associated to PA. In the present work, we evaluate whether a hypothermia mimetic small molecule, zr17-2, has similar effects in the context of PA.

Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy.

Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-approved anti-anginal drug ranolazine (RANO) delays tumour recurrence with acquired BRAFi resistance.

Identification of 7-Ketocholesterol-Modulated Pathways and Sterculic Acid Protective Effect in Retinal Pigmented Epithelium Cells by Using Genome-Wide Transcriptomic Analysis.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. AMD is characterized by the formation of lipidic deposits between the retinal pigment epithelium (RPE) and the choroid called drusen. 7-Ketocholesterol (7KCh), an oxidized-cholesterol derivative, is closely related to AMD as it is one of the main molecules accumulated in drusen.

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.

A hypothermia mimetic molecule (zr17-2) reduces ganglion cell death and electroretinogram distortion in a rat model of intraorbital optic nerve crush (IONC).

Ocular and periocular traumatisms may result in loss of vision. Our previous work showed that therapeutic hypothermia prevents retinal damage caused by traumatic neuropathy. We also generated and characterized small molecules that elicit the beneficial effects of hypothermia at normal body temperature.

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (CRT) is one of the standards of care in locally advanced rectal cancer (LARC). This retrospective study examines clinical, analytical, and pathological parameters collected from 77 patients with locally advanced (cT3-4 or cN+) rectal carcinoma diagnosed between 2007 and 2017 at our institution that were treated with preoperative CRT and surgery. In the prognosis analysis, lower hemoglobin levels ( = 0.

CB1 Cannabinoid Receptor is a Target for Neuroprotection in Light Induced Retinal Degeneration.

In the last few years, an increasing interest in the neuroprotective effect of cannabinoids has taken place. The aim of the present work was to study the effects of modulating cannabinoid receptor 1 (CB1) in the context of light induced retinal degeneration (LIRD), using an animal model that resembles many characteristics of human age-related macular degeneration (AMD) and other degenerative diseases of the outer retina. Sprague Dawley rats ( = 28) were intravitreally injected in the right eye with either a CB1 agonist (ACEA), or an antagonist (AM251).

The Regulators of Peroxisomal Acyl-Carnitine Shuttle CROT and CRAT Promote Metastasis in Melanoma.

Circulating tumor cells are the key link between a primary tumor and distant metastases, but once in the bloodstream, loss of adhesion induces cell death. To identify the mechanisms relevant for melanoma circulating tumor cell survival, we performed RNA sequencing and discovered that detached melanoma cells and isolated melanoma circulating tumor cells rewire lipid metabolism by upregulating fatty acid (FA) transport and FA beta-oxidation‒related genes. In patients with melanoma, high expression of FA transporters and FA beta-oxidation enzymes significantly correlates with reduced progression-free and overall survival.

Biomarkers as Predictive Factors of Anti-VEGF Response.

Age-related macular degeneration is the main cause of irreversible vision in developed countries, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the current gold standard treatment today. Although anti-VEGF treatment results in important improvements in the course of this disease, there is a considerable number of patients not responding to the standardized protocols. The knowledge of how a patient will respond or how frequently retreatment might be required would be vital in planning treatment schedules, saving both resource utilization and financial costs, but today, there is not an ideal biomarker to use as a predictive response to ranibizumab therapy.

Adenosine A2A Receptor: A New Neuroprotective Target in Light-Induced Retinal Degeneration.

Continuous illumination induces the degeneration of photoreceptors. This animal model of light-induced retinal degeneration resembles many characteristics of human degenerative diseases of the outer retina, such as age-related macular degeneration. This work aimed to evaluate the potential neuroprotective effect of the modulation of adenosine A2A receptor in the model of light-induced retinal degeneration.

Predictive Biomarkers of Age-Related Macular Degeneration Response to Anti-VEGF Treatment.

Age-related macular degeneration (AMD) is an incurable disease associated with aging that destroys sharp and central vision. Increasing evidence implicates both systemic and local inflammation in the pathogenesis of AMD. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is currently the first-line therapy for choroidal neovascularization in AMD patients.

Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells.

Sterculic acid (SA) is a cyclopropenoid fatty acid isolated from seeds. This molecule is a well-known inhibitor of SCD1 enzyme, also known as ∆9-desaturase, which main function is related to lipid metabolism. However, recent studies have demonstrated that it also modifies many other pathways and the underlying gene expression.

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.

Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats.

Perinatal asphyxia (PA) can cause retinopathy and different degrees of visual loss, including total blindness. In a rat model of PA, we have previously shown a protective effect of hypothermia on the retina when applied simultaneously with the hypoxic insult. In the present work, we evaluated the possible protective effect of hypothermia on the retina of PA rats when applied immediately after delivery.

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.

Neuroprotective Effect of Apolipoprotein D in Cuprizone-Induced Cell Line Models: A Potential Therapeutic Approach for Multiple Sclerosis and Demyelinating Diseases.

Apolipoprotein D (Apo D) overexpression is a general finding across neurodegenerative conditions so the role of this apolipoprotein in various neuropathologies such as multiple sclerosis (MS) has aroused a great interest in last years. However, its mode of action, as a promising compound for the development of neuroprotective drugs, is unknown. The aim of this work was to address the potential of Apo D to prevent the action of cuprizone (CPZ), a toxin widely used for developing MS models, in oligodendroglial and neuroblastoma cell lines.

Methylene Blue Prevents Retinal Damage Caused by Perinatal Asphyxia in the Rat.

Perinatal asphyxia (PA) is responsible for a large proportion of neonatal deaths and numerous neurological sequelae, including visual dysfunction and blindness. In PA, the retina is exposed to ischemia/reoxygenation, which results in nitric oxide (NO) overproduction and neurotoxicity. We hypothesized that methylene blue (MB), a guanylyl cyclase inhibitor, and free-radical scavenger currently used in the clinic, may block this pathway and prevent PA-induced retinal degeneration.

Genome-Wide Transcriptomic Analysis Identifies Pathways Regulated by Sterculic Acid in Retinal Pigmented Epithelium Cells.

In addition to its predominant role in lipid metabolism and body weight control, has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is a cyclopropene fatty acid with numerous biological activities, generally attributed to its Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently of SCD inhibition, may be mediating anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD), but the mechanisms involved are poorly understood.

Sterculic Acid: The Mechanisms of Action beyond Stearoyl-CoA Desaturase Inhibition and Therapeutic Opportunities in Human Diseases.

In many tissues, stearoyl-CoA desaturase 1 (SCD1) catalyzes the biosynthesis of monounsaturated fatty acids (MUFAS),(i.e., palmitoleate and oleate) from their saturated fatty acid (SFA) precursors (i.

Inflammatory and cell death mechanisms induced by 7-ketocholesterol in the retina. Implications for age-related macular degeneration.

This review will focus on the inflammatory and toxic mechanism of action of 7-ketocholesterol (7KCh) and the potential implications of its accumulation, especially in the retina. 7KCh is a pro-inflammatory oxysterol usually associated with oxidized lipoprotein deposits present in aged retinas. High amounts of 7KCh can be generated in situ in these lipoprotein deposits possibly through a free radical-mediated mechanism catalyzed by iron.

Integrins: Moonlighting Proteins in Invadosome Formation.

Invadopodia are actin-rich protrusions developed by transformed cells in 2D/3D environments that are implicated in extracellular matrix (ECM) remodeling and degradation. These structures have an undoubted association with cancer invasion and metastasis because invadopodium formation in vivo is a key step for intra/extravasation of tumor cells. Invadopodia are closely related to other actin-rich structures known as podosomes, which are typical structures of normal cells necessary for different physiological processes during development and organogenesis.