Unraveling AURKB as a potential therapeutic target in pulmonary hypertension using integrated transcriptomic analysis and pre-clinical studies.

Despite advances in treatment, the prognosis for patients with pulmonary arterial hypertension (PAH) remains dismal, highlighting the need for further therapeutic advances. By using RNA sequencing on pulmonary artery smooth muscle cells (PASMCs), functional enrichment, and connectivity map analyses, we identify Aurora kinase B (AURKB) as a candidate therapeutic target. We show that AURKB inhibition blocks cell cycle progression and reverses the gene signature of PAH-PASMCs.

Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.

Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

Impact of pharmacist-led interventions in identifying and resolving drug related problems and potentially inappropriate prescriptions among rural patients: A pilot study.

Background: Drug-related problems are a major problem that can lead to increased morbidity, mortality, and healthcare costs due to heightened medical visits, hospital readmissions, or emergency room visits. In rural areas, new tools for clinical pharmacy services, such as medication review, could decrease this problem.

Objective: To analyze the prevalence of clinically relevant drug-related problems (DRPs) and potentially inappropriate prescriptions (PIPs) identified by new medication review software (Revisem®) in rural pharmacies.

[Analysis and categorization of pharmacotherapeutic queries received at a Valencia Drug Information Center].

Introduction: Drug Information Services (DIS) act as a source of technical and scientific information of drugs and medical devices, promoting their rational use.

Objective: To analyze and classify, according to standardized criteria, the pharmacotherapeutic queries, therapeutic groups, and drugs most frequently consulted at the DIS of the Muy Ilustre Colegio Oficial de Farmacéuticos de Valencia (MICOF).

Methodology: An ambispective and cross-sectional observational study was conducted from June 1, 2021, to June 1, 2022.

Freezing-Tolerant Supramolecular Adhesives from Tannic Acid-Based Low-Transition-Temperature Mixtures.

Natural polyphenols like tannic acid (TA) have recently emerged as multifunctional building blocks for designing advanced materials. Herein, we show the benefits of having TA in a dynamic liquid state using low-transition-temperature mixtures (LTTMs) for developing freezing-tolerant glues. TA was combined with betaine or choline chloride to create LTTMs, which direct the self-assembly of guanosine into supramolecular viscoelastic materials with high adhesion.

Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights from Comprehensive Multicenter Preclinical Studies.

Unlabelled: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PA) and progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Although several drugs are approved for the treatment of PAH, mortality remains high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression.

Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1β maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107-111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models.

Cyclosporin A-loaded dissolving microneedles for dermatitis therapy: Development, characterisation and efficacy in a delayed-type hypersensitivity in vivo model.

Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to systemic side effects from occurring. Cyclosporin A (CsA) has been used for this purpose; however, its high molecular weight (1202 Da) restricts the diffusion through the skin structure.

Adenosine A receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia.

Adenosine regulates multiple physiological processes through the activation of four receptor subtypes, of which the A adenosine receptor (AAR) has the lowest affinity for adenosine. Being the adenosine receptor subtype most prominently expressed in epidermis, we recently described the antiproliferative and anti-inflammatory effect of the selective AAR agonist BAY60-6583 (BAY) in human keratinocytes stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), so we sought to establish the effect of topical application of BAY in a model of murine epidermal hyperplasia. Topical application of BAY (1 or 10 μg/site) prevented the inflammatory reaction and skin lesions induced by TPA, minimizing hyperproliferation and acanthosis, as well as the expression of specific markers of proliferative keratinocytes.

Prognostic factors in young women with epithelial ovarian cancer: the Young Ovarian Cancer-Care (YOC-Care) study.

Objective: To determine oncological outcomes and to identify prognostic factors in women aged <45 years with epithelial ovarian cancer.

Methods: A multicenter retrospective study was performed of patients treated for epithelial ovarian cancer aged <45 years between January 2010 and December 2019.

Results: A total of 998 patients with epithelial ovarian cancer from 55 different institutions in Spain were collected.

Adipose Tissue Protects against Hepatic Steatosis in Male Rats Fed a High-Fat Diet plus Liquid Fructose: Sex-Related Differences.

Non-alcoholic fatty liver disease is a sexual dimorphic disease, with adipose tissue playing an essential role. Our previous work showed that female rats fed a high-fat high-fructose diet devoid of cholesterol (HFHFr) developed simple hepatic steatosis dissociated from obesity. This study assessed the impact of the HFHFr diet on the male rat metabolism compared with data obtained for female rats.

Evaluation of Control Strategies for in the Balearic Islands.

The emergence of (Xf) in the Balearic Islands in October 2016 was a major phytosanitary challenge with international implications. Immediately after its detection, eradication and containment measures included in Decision 2015/789 were implemented. Surveys intensified during 2017, which soon revealed that the pathogen was widely distributed on the islands and eradication measures were no longer feasible.

Global predictions for the risk of establishment of Pierce's disease of grapevines.

The vector-borne bacterium Xylella fastidiosa is responsible for Pierce's disease (PD), a lethal grapevine disease that originated in the Americas. The international plant trade is expanding the geographic range of this pathogen, posing a new threat to viticulture worldwide. To assess the potential incidence of PD, we have built a dynamic epidemiological model based on the response of 36 grapevine varieties to the pathogen in inoculation assays and on the vectors' distribution when this information is available.

Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques.

Administration of a novel and selective small molecule integrin αvβ6 inhibitor, MORF-627, to young cynomolgus monkeys for 28 days resulted in the rapid induction of epithelial proliferative changes in the urinary bladder of 2 animals, in the absence of test agent genotoxicity. Microscopic findings included suburothelial infiltration by irregular nests and/or trabeculae of epithelial cells, variable cytologic atypia, and high mitotic rate, without invasion into the tunica muscularis. Morphologic features and patterns of tumor growth were consistent with a diagnosis of early-stage invasive urothelial carcinoma.

Proteomic characterization of spinal cord synaptoneurosomes from Tg-SOD1/G93A mice supports a role for MNK1 and local translation in the early stages of amyotrophic lateral sclerosis.

The isolation of synaptoneurosomes (SNs) represents a useful means to study synaptic events. However, the size and density of synapses varies in different regions of the central nervous system (CNS), and this also depends on the experimental species studied, making it difficult to define a generic protocol for SNs preparation. To characterize synaptic failure in the spinal cord (SC) in the Tg-SOD1/G93A mouse model of amyotrophic lateral sclerosis (ALS), we applied a method we originally designed to isolate cortical and hippocampal SNs to SC tissue.

Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling.

Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events.

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO.

Background: To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).

Methods: The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years).

Single-Cell Transcriptomics Reveal Disrupted Kidney Filter Cell-Cell Interactions after Early and Selective Podocyte Injury.

The health of the kidney filtration barrier requires communication among podocytes, endothelial cells, and mesangial cells. Disruption of these cell-cell interactions is thought to contribute to disease progression in chronic kidney diseases (CKDs). Podocyte ablation via doxycycline-inducible deletion of an essential endogenous molecule, CTCF [inducible podocyte-specific CTCF deletion (iCTCF)], is sufficient to drive progressive CKD.

Activation of the Constitutive Androstane Receptor Inhibits Leukocyte Adhesiveness to Dysfunctional Endothelium.

Leukocyte cell recruitment into the vascular subendothelium constitutes an early event in the atherogenic process. As the effect of the constitutive androstane receptor (CAR) on leukocyte recruitment and endothelial dysfunction is poorly understood, this study investigated whether the role of CAR activation can affect this response and the underlying mechanisms involved. Under physiological flow conditions, TNFα-induced endothelial adhesion of human leukocyte cells was concentration-dependently inhibited by preincubation of human umbilical arterial endothelial cells with the selective human CAR ligand CITCO.

[Value of the intraoperative pathology in thyroid surgery. Comparison with preoperative aspiration puncture and deferred pathology].

To evaluate the usefulness of intraoperative pathology (IP) in thyroid surgery, a retrospective review of its results in 350 patients was performed in comparison with the results of the preoperative fine-needle biopsy (FNB) and the surgical pathology report (SPR). The FNB was reported according to the Bethesda system as type II in 91 cases (26.0%), type III in 21 (6.

Smart material based on boron crosslinked polymers with potential applications in cancer radiation therapy.

Organoboron compounds have been playing an increasingly important role in analytical chemistry, material science, health applications, and particularly as functional polymers like boron carriers for cancer therapy. There are two main applications of boron isotopes in radiation cancer therapy, Boron Neutron Capture Therapy and Proton Boron Fusion Therapy. In this study, a novel and original material consisting of a three-dimensional polymer network crosslinked with [Formula: see text]B enriched boric acid molecules is proposed and synthesized.

Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD).