Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19.

Background: There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified.

Transitions in cell potency during early mouse development are driven by Notch.

The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage.

Site-Specific Antibody Drug Conjugates Using Streamlined Expressed Protein Ligation.

Antibody-Drug Conjugates (ADCs) have been shown to produce clinical benefit in cancer patient thanks to their ability to target highly cytotoxic small molecules to tumor cells. However, the development of these complex molecules faces significant challenges due to the need to combine a large biologic drug with a small molecule drug to generate the desired bioconjugate. We describe here the use of a protein ligation methodology, based on the native chemical ligation reaction to generate site-specific Antibody-Drug Conjugates, which does not require the incorporation of unnatural modifications into the antibody.

Unraveling Surface Proteins Using Cell Shaving Proteomics.

is one of the main etiologic agents of bacterial vaginosis (BV). This infection is responsible for a wide range of public health costs and is associated with several adverse outcomes during pregnancy. Improving our understanding of protein cell surface will assist in BV diagnosis.

S100A7: from mechanism to cancer therapy.

Within the tumor, malignant and stromal cells support each other by secreting a wide variety of growth factors and cytokines, allowing tumor growth and disease progression. The identification and regulation of those key factors in this crosstalk has opened the opportunity to develop new therapeutic strategies that not only act on the tumor cells but also on the stroma. Among these factors, S100A7 protein has gained interest in the last years.

Late complications of percutaneous tracheostomy using the balloon dilation technique.

Objective: The purpose of this study was to determine the late complications in critically ill patients requiring percutaneous tracheostomy (PT) using the balloon dilation technique.

Design: A prospective, observational cohort study was carried out.

Scope: Two medical-surgical intensive care units (ICU).

RCAN 1 and 3 proteins regulate thymic positive selection.

Cooperation between calcineurin (CN)-NFATc and RAF-MEK-ERK signaling pathways is essential in thymocyte positive selection. It is known that the Regulators of Calcineurin (RCAN) proteins can act either facilitating or suppressing CN-dependent signaling events. Here, we show that RCAN genes are expressed in lymphoid tissues, and address the role of RCAN proteins in T cell development.

In vivo anticancer evaluation of the hyperthermic efficacy of anti-human epidermal growth factor receptor-targeted PEG-based nanocarrier containing magnetic nanoparticles.

Polymeric nanoparticles with targeting moieties containing magnetic nanoparticles as theranostic agents have considerable potential for the treatment of cancer. Here we report the chemical synthesis and characterization of a poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-based nanocarrier containing iron oxide nanoparticles and human epithelial growth factor receptor on the outer shell. The nanocarrier was also radiolabeled with (99m)Tc and tested as a theranostic nanomedicine, ie, it was investigated for both its diagnostic ability in vivo and its therapeutic hyperthermic effects in a standard A431 human tumor cell line.

S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer.

Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prognosis of all solid malignant tumors. Recent evidences suggest that the metastasis-promoting protein S100P stimulates pancreatic tumor proliferation, survival, invasion and metastasis progression through extracellular functions. Moreover, its expression is strongly correlated with poor prognosis in patients with several types of cancer although the entire molecular mechanism responsible for the diverse biological functions is not fully understood.

Tackling lipophilicity of peptide drugs: replacement of the backbone N-methyl group of cilengitide by N-oligoethylene glycol (N-OEG) chains.

Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was was developed as a highly active and selective ligand for the αvβ3 and αvβ5 integrin receptors. We describe the synthesis of three analogues of this peptide in which the N-Me group has been replaced by N-oligoethylene glycol (N-OEG) chains of increasing size: namely N-OEG2, N-OEG11, and N-OEG23, which are respectively composed of 2, 11, and 23 ethylene oxide monomer units. The different N-OEG cyclopeptides and the original peptide were compared with respect to lipophilicity and biological activity.

Micropattern of antibodies imaged by shear force microscopy: comparison between classical and jumping modes.

Quartz tuning fork devices are increasingly being used as nanosensors in Scanning Probe Microscopy. They offer some benefits with respect to standard microfabricated cantilevers in certain experimental setups including the study of biomolecules under physiological conditions. In this work, we compare three different working modes for imaging micropatterned antibodies with quartz tuning fork sensors: apart from the classical amplitude and frequency modulation strategies, for first time the jumping mode is implemented using tuning forks.

Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody.

S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model.

The backbone N-(4-azidobutyl) linker for the preparation of peptide chimera.

A robust synthetic strategy for the introduction of the N-(4-azidobutyl) linker into peptides using standard SPPS techniques is described. Based on the example of Cilengitide it is shown that the N-(4-azidobutyl) group exerts similar conformational restraints as a backbone N-Me group and allows conjugation of a desired molecule either via click chemistry or-after azide reduction-via acylation or reductive alkylation.

Dual effects of β3 integrin subunit expression on human pancreatic cancer models.

Background: Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.

Methods: In view of these findings, we examined the role of β(3) in pancreatic cancer by generating two stable β(3)-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.

Dual effects of β3 integrin subunit expression on human pancreatic cancer models.

Background: pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.

Methods: in view of these findings, we examined the role of β3 in pancreatic cancer by generating two stable β3-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.

Overexpression of S100A4 in human cancer cell lines resistant to methotrexate.

Background: Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance.

[Applicability of the ICF in measuring functioning and disability in unipolar depression in Primary Care settings].

Introduction: We use the biopsychosocial model of the International Classification of Functioning, Disability, and Health (ICF): a) to analyze functioning and disability patterns in unipolar depression cases attended in primary care settings; b) to study predictive and mediator variables related to disability in depression, and c) to determine the impact of traditional interventions in depression cases using functional remission as outcome measure.

Design: Naturalistic, prospective, longitudinal.

Setting: Multicenter study in primary care.

Anti-migratory and anti-angiogenic effect of p16: a novel localization at membrane ruffles and lamellipodia in endothelial cells.

Recent evidence has established different functions for the tumor suppressor protein, p16(INK4A) aside from controlling the cell cycle. Here we report that cdk4/6 inhibition blocked both human umbilical vein endothelial cells (HUVEC) spreading on a vitronectin matrix and HUVEC migration on vitronectin. p16 can also act as an anti-angiogenic molecule in vitro since HUVEC and HMEC cells transfected with Ad-p16 or treated with Antennapedia p16 peptides are unable to differentiate on a Matrigel matrix.

[Vagus nerve stimulation and psychosis. A single case report].

The appearance of behavioral disorders in the context of a decrease in the number of seizures in epileptic patients is a fact that was already described in Landolt's theory of forced normalization in the middle of the XX century. Through this clinical case, we propose several mechanisms that aim to give a general explanation to the physiopathology of this condition. Among them, the theory which suggests increased alertness as a result of inhibitory mechanisms secondary to a long lasting epileptic condition stands out.

Use of siRNAs and antisense oligonucleotides against survivin RNA to inhibit steps leading to tumor angiogenesis.

The antiapoptotic protein survivin is an attractive target in cancer therapy because it is expressed differently in tumors and normal tissues and it is potentially required for cancer cells to remain viable. Given that survivin is also overexpressed in endothelial cells (ECs) of newly formed blood vessels found in tumors, its RNA targeting might compromise EC viability and interfere with tumor angiogenesis. We used two antisense strategies against survivin expression, antisense oligonucleotides (aODN) and small interfering RNA (siRNA), to study in ECs the contribution of survivin in various steps leading to tumor angiogenesis.

Serum amino acid levels after permanent middle cerebral artery occlusion in the rat.

Background And Purpose: High levels of glutamate in plasma and cerebrospinal fluid (CSF) have been demonstrated in patients with acute ischemic stroke. Whereas this glutamate increase in CSF is only evidenced during the first 6 h in stable ischemic stroke, it is sustained for 24 h in progressing stroke. The aim of this investigation was to study the evolution of serum glutamate levels after stroke in a rat model of permanent cerebral artery occlusion.

Pharmacokinetics of oligodeoxynucleotides encapsulated in liposomes: effect of lipid composition and preparation method.

1. The effect of the method employed to prepare liposomes and their lipid composition were evaluated in terms of the encapsulation efficiency and pharmacokinetic features of two oligodeoxynucleotides of a 21 mer: the normal (N-Odn) and the phosphorothioate (S-Odn) oligodeoxynucleotide. 2.

In vitro and in vivo protective effect of orphenadrine on glutamate neurotoxicity.

The anticholinergic drug orphenadrine is used in the treatment of Parkinson's disease. In this study we evaluate the neuroprotective effects of orphenadrine on excitotoxicity in vivo and in vitro. Orphenadrine prevented the mitochondrial and the cytoplasmic membrane potential decrease evoked by NMDA (100 microM) in rat dissociated cerebellar granule cells showing an IC50 value of 11.