1,357,593 research outputs found
Jinghan Li (Alex)_SURF2025_Evaluation of CRISPR/Cas9-Based Gene Fragment Deletion in Primary Human Chondrocytes using the Pregnancy-Associated Plasma Protein A (PAPPA) Gene as Target
No full textOsteoarthritis (OA) is the most common joint disorder, impacting more than 500 million people worldwide, and has become increasingly prominent in the past two decades. It can lead to serious health and economic burden, while there is currently no curative treatment for OA because its disease development is complex. Genetic factors are the top contributing factors of OA, and it is imperative to understand the genetic basis of OA. Pregnancy-associated plasma protein A (PAPPA) is a novel gene identified to be involved in OA development with support of genome-wide association studies (GWAS), expression quantitative trait loci (eQTL), and high-throughput chromatin conformation capture (Hi-C) data. This study used primary human chondrocytes as the model system and employed ribonucleoprotein transfection-based CRISPR/Cas9 delivery to create two double-stranded breaks in the exon 2 of the PAPPA gene in these cells. Screening of the population following transfection showed that a significant number of cells have undergone a deletion in the exon 2 of PAPPA, which will putatively generate a knock-out (KO) of the PAPPA gene. Single colonies were then isolated and expanded from the transfected population, and multiple colonies of cells with homozygous deletion of a region in PAPPA exon 2 were identified. These colonies of cells are highly valuable for functional follow-up experiments on changes in gene expression and phenotypes of chondrocytes with PAPPA KO, which will be performed subsequently. In summary, this study further verified the feasibility of generating gene fragment deletions using CRISPR/Cas9 in chondrocytes and has laid the basis for the functional studies of PAPPA as a potential key mediator of OA.
Placental expression of PAPPA, PAPPA-2 and PLAC-1 in pregnacies is associated with FGR
No full textFetal growth restriction (FGR) is a gynecological disorder of varying etiology. In the present study, an expression analysis of pregnancy-associated plasma protein A (PAPPA), pregnancy-associated plasma protein A2 (PAPPA2) and placenta-specific-1 (PLAC-1) was conducted in pregnancies with FGR and control pregnancies. Placental tissues were collected from pregnancies with FGR (n=16) and control pregnancies (n=16) and the expression of the genes of interest was examined by qPCR. The mean expression levels of PAPPA and PAPPA2 were significantly lower (P<0.001) in placental tissues from FGR pregnancies compared with tissues from healthy subjects, whereas the opposite pattern was observed for PLAC-1 (P<0.001). PAPPA and PLAC-1 expression in FGR and control subjects correlated with birth weight (P<0.001). The findings suggest a possible pathophysiological link between the development of FGR and the expression of PAPPA, PAPPA2 and PLAC-1. © 2018 Spandidos Publications. All rights reserved
PAPPA knockdown in A549 cells lines.
No full text<p>A549 cells were transduced with lentiviral particles containing shRNAmir (#81 #82 and #83) to PAPPA and non-silencing shRNAmir (SC) and selected with puromycin. (A) PAPPA mRNA levels from these cell lines determined by real-time PCR quantification and depicted as relative level to non-silencing control. (B) IGF dependent protease activity in conditioned medium from PAPPA knockdown A549 cells lines. (C) Growth curve of PAPPA knockdown A549 cells line #82 and non-silencing control line.</p
PAPPA expression in HSCs and HCC tissues.
No full text<p>PAPPA protein levels in conditioned media, correlation of protein and mRNA levels, and correlation with collagen. A. PAPPA levels in conditioned media of HSCs from 15 different human donors. B. Correlation of PAPPA protein levels and mRNA levels in HSCs from 15 different human donors. C. Correlation of PAPPA and collagen I (COL1A1) mRNA expression in 51 human HCC tissues.</p
PAPPA Expression in Indeterminate Thyroid Nodules as Screening Test to Select Patients for Molecular Testing
No full textPregnancy-associated plasma protein A (PAPPA) acts as an oncogene, and its expression is increased in multiple malignancies, including thyroid cancer. Molecular tests represent a useful tool in the management of indeterminate thyroid nodules; however, they are not conducted in all centers, and they contribute to increase the per-patient cost of nodule evaluation. In this study, we examined whether PAPPA expression could represent a promising new screening test in the management of indeterminate thyroid nodules. Toward this aim, PAPPA expression was evaluated in 107 fine needle aspiration cytologies (FNAC) belonging to Bethesda III–IV categories that had been sent to molecular biology to discriminate the nature of the nodules. We found that the PAPPA expression increased and showed an elevated sensitivity (97.14%) and negative predictive value (98%) in indeterminate cytological samples positive for mutations. The enhanced expression was not linked to a specific oncogene. Our findings demonstrated that assessing the PAPPA expression in indeterminate thyroid cytologies could represent a useful screening tool to select all patients that effectively need to be sent to molecular testing, thereby, leading to a potential cost reduction in the management of patients
Paa sinä pappa (2/4 a)
No full textLaulun sanat: Paa, sinä pappa, se pikku musta terävään rengaskenkään, hei, allan tulatula, allan lei, terävään rengaskenkään
The “Pappa di Parma” integrated approach against moderate acute malnutrition
No full textThe use of Ready-to-Use Therapeutic Foods (RUTFs) is not a sustainable strategy to treat child moderate acute malnutrition due to its high cost and unfamiliarity. An integrated multidisciplinary approach called “Pappa di Parma” was used to develop, characterize and introduce alternative sustainable and energy-dense meals against malnutrition. Six formulations were developed by using basic accessible technologies and locally available ingredients (Tanzania), a daily portion of which meets RUTFs macronutrient requirements and most micronutrients RNI. Quality characterization, rheological properties and shelf-stability of formulae were assessed under different storage conditions disclosing the suitability and stability of no-water formulae in all tested storage conditions for almost under three months. Moreover, the cultural acceptance and the economical sustainability through the implementation in Tanzania were also evaluated. Overall, this study confirmed the “Pappa di Parma” approach as a valid starting point to sustainable alternatives to RUTFs, tailored to specific agricultural and socio-economic contexts
Correction to: The role of intra-articular administration of Fetuin-A in post-traumatic knee osteoarthritis: an experimental study in a rat model (Journal of Experimental Orthopaedics, (2019), 6, 1, (25), 10.1186/s40634-019-0194-4)
No full textFollowing publication of the original article (Pappa et al. 2019), the authors opted to correct the middle initial of co-author Despina N. Perrea from S to N. The original article has been corrected. © 2019, The Author(s)
Studio preliminare sulla pappa reale: aspetti inerenti l'azione antimicrobica
No full textAl fine di verificare se anche la pappa reale, analogamente al miele, sia dotata di attività antimicrobica, sono stati analizzati diversi campioni di pappa reale provenienti dall’Emilia Romagna valutandone la capacità di inibire la crescita sia di lieviti (Saccharomyces cerevisiae, Yarrowia lipolytica e Debaryomyces hansenii), che di diversi ceppi della specie Aspergillus niger. Tale prodotto dell’alveare non ha mostrato alcun effetto sui lieviti. Un aspetto molto interessante che è stato invece osservato per tutti i ceppi di Aspergillus niger analizzati è stata la comparsa di una colorazione nera nella zona immediatamente circostante quella di deposizione della pappa reale probabilmente dovuta alla produzione di melanine. Molti funghi producono infatti pigmenti melaninici, di colore bruno o nero, per polimerizzazione ossidativa dei composti fenolici attraverso un meccanismo, comune a molti sistemi biologici, che coinvolge l’azione della poli-fenolossidasi. L’azione stimolante della pappa reale osservata nei confronti dell’attivazione della poli-fenolossidasi fa ritenere che nella pappa reale possano essere presenti segnalatori comuni in grado di indurre l’espressione di tale enzima sia nei funghi, che nelle larve. Tale ipotesi ha trovato riscontro nell’analisi gascromatografica (GC-SPME) della pappa reale che ha evidenziato la presenza di una molecola, e precisamente il 3-idrossi-4-dimetil- ammino-metil-2-furanone, che potrebbe agire come molecola segnalatrice. Infatti i furanoni sono molecole naturali che partecipano ad un’ampia varietà di fenomeni biologici includenti anche i meccanismi di segnalazione tra i microrganismi
PAPPA expression in human HCC tissues of different tumor stages.
No full text<p>PAPPA mRNA expression levels in human HCC tissues (n = 52) of tumor stages I (n = 12), II (n = 19) and III (n = 21). One-way ANOVA shows a significant effect (p = 0.008) of tumor stage on PAPPA mRNA expression level.</p
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