Mairobi Persinal-Medina  Sara Llames  Manuel Chacn  Natalia Vzquez  Marta Pevida  Ignacio Alcalde  Sergio Alonso-Alonso  Laura María Martínez-Lpez  Jesús Merayo-Lloves  lvaro Meana 《International journal of molecular sciences》2022,23(9)

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically. In this study, we describe the development of a polymerizable skin hydrogel consisting of keratinocytes and fibroblast entrapped within a fibrin scaffold. We histologically characterized the construct and evaluated its use on an in vivo wound healing model of skin damage. Our results indicate that the proposed methodology can be used to effectively regenerate skin wounds, avoiding the secondary in vitro culture steps and thus, shortening the time needed until transplantation in comparison with other bilayer skin models. This is achievable due to the instant polymerization of the keratinocytes and fibroblast combination that allows a direct application on the wound. We suggest that the polymerizable skin hydrogel is an inexpensive, easy and rapid treatment that could be transferred into clinical practice in order to improve the treatment of skin wounds.  相似文献   

    

Piotr Was&#x;g  Anna Suwi&#x;ska  Marta Lenartowska  Robert Lenartowski 《International journal of molecular sciences》2022,23(9)

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Marta Brzozowska  Marta Romaniewicz  Jaros&#x;aw Ca&#x;ka  Barbara Jana 《International journal of molecular sciences》2022,23(21)

Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP) and neurokinin A (NKA), are involved in controlling uterine function. Here, we determined the effect of Escherichia coli (E. coli)-induced inflammation on expression of protein receptor subtypes for substance P (NK1R) and neurokinin A (NK2R) in the pig myometrium as well as their role in contractility of inflamed uterus. The severe acute endometritis developed in the E. coli group and the expression of NK1R and NK2R proteins increased in the myometrium. Compared to the pre-administration period, SP (10⁻⁶ M) reduced the amplitude and frequency in the myometrium of the E. coli group and the amplitude was higher and the frequency was lower versus other groups. NKA reduced the amplitude and increased the frequency in endometrium/myometrium of the E. coli group. In this group, the amplitude was lower and the frequency was higher than in the CON and SAL groups. Our research showed that NK2R (10⁻⁶ M) antagonist application abolished the NKA inhibitory effect on uterine amplitude. The application of the NK1R (10⁻⁵ M) antagonist together with SP revealed that the inhibitory effect of SP on uterine contractility is achieved independently of the NKR1. Additionally, taking into account the fact that NKA shows an inhibitory effect with the use of NK2R on uterine amplitude suggests the possibility of therapeutic use of the antagonist as a drug increasing uterine contractility in inflammation.  相似文献   

    

Antonio Matera  Alessio Marella  Akihiro Maeda  Matteo C. Da Vi  Francesca Lazzaroni  Sonia Fabris  Stefania Pioggia  Laura Porretti  Federico Colombo  Federica Torricelli  Antonino Neri  Elisa Taiana  Giuseppina Fabbiano  Valentina Traini  Elisa Genuardi  Daniela Drandi  Niccol Bolli  Marta Lionetti 《International journal of molecular sciences》2022,23(24)

Multiple myeloma (MM) has a highly heterogeneous genetic background, which complicates its molecular tracking over time. Nevertheless, each MM patient’s malignant plasma cells (PCs) share unique V(D)J rearranged sequences at immunoglobulin loci, which represent ideal disease biomarkers. Because the tumor-specific V(D)J sequence is highly expressed in bulk RNA in MM patients, we wondered whether it can be identified by single-cell RNA sequencing (scRNA-seq). To this end we analyzed CD138⁺ cells purified from bone marrow aspirates of 19 samples with PC dyscrasias by both a standard method based on bulk DNA and by an implementation of the standard 10x Genomics protocol to detect expressed V(D)J sequences. A dominant clonotype was easily identified in each sample, accounting on average for 83.65% of V(D)J-rearranged cells. Compared with standard methods, scRNA-seq analysis proved highly concordant and even more effective in identifying clonal productive rearrangements, by-passing limitations related to the misannealing of consensus primers in hypermutated regions. We next validated its accuracy to track 5 clonal cells with absolute sensitivity in a virtual sample containing 3180 polyclonal cells. This shows that single-cell V(D)J analysis may be used to find rare clonal cells, laying the foundations for functional single-cell dissection of minimal residual disease.  相似文献   

    

Marta Szandruk-Bender  Benita Wiatrak  Stanis&#x;aw Dzimira  Anna Merwid-L&#x;d  &#x;ukasz Szczukowski  Piotr wi&#x;tek  Adam Szel&#x;g 《International journal of molecular sciences》2022,23(17)

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Ombretta Repetto  Laura Caggiari  Mariangela De Zorzi  Caterina Elia  Lara Mussolin  Salvatore Buffardi  Marta Pillon  Paola Muggeo  Tommaso Casini  Agostino Steffan  Christine Mauz-Krholz  Maurizio Mascarin  Valli De Re 《International journal of molecular sciences》2022,23(17)

Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, p < 0.05, Student’s t-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (p < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial.  相似文献   

    

Carlos Casas-Arozamena  Alexandra Cortegoso  Raquel Pieiro-Perez  Alicia Abalo  Efigenia Arias  Victoria Sampayo  Ana Vilar  Marta Bouso  Eva Diaz  Gema Moreno-Bueno  Rafael Lpez-Lpez  Laura Muinelo-Romay  Miguel Abal  Juan Cueva 《International journal of molecular sciences》2022,23(15)

Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies.  相似文献   

    

Beata Podgrska  Marta Wielogrska-Partyka  Joanna Godzie&#x;  Julia Siemi&#x;ska  Micha&#x; Ciborowski  Ma&#x;gorzata Szelachowska  Adam Kr&#x;towski  Katarzyna Siewko 《International journal of molecular sciences》2022,23(18)

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.  相似文献   

    

Marta Vallverdú-Prats  Ramon Brugada  Mireia Alcalde 《International journal of molecular sciences》2022,23(2)

Arrhythmogenic cardiomyopathy is a heritable heart disease associated with desmosomal mutations, especially premature termination codon (PTC) variants. It is known that PTC triggers the nonsense-mediated decay (NMD) mechanism. It is also accepted that PTC in the last exon escapes NMD; however, the mechanisms involving NMD escaping in 5′-PTC, such as reinitiation of translation, are less known. The main objective of the present study is to evaluate the likelihood that desmosomal genes carrying 5′-PTC will trigger reinitiation. HL1 cell lines were edited by CRISPR/Cas9 to generate isogenic clones carrying 5′-PTC for each of the five desmosomal genes. The genomic context of the ATG in-frame in the 5′ region of desmosomal genes was evaluated by in silico predictions. The expression levels of the edited genes were assessed by Western blot and real-time PCR. Our results indicate that the 5′-PTC in PKP2, DSG2 and DSC2 acts as a null allele with no expression, whereas in the DSP and JUP gene, N-truncated protein is expressed. In concordance with this, the genomic context of the 5′-region of DSP and JUP presents an ATG in-frame with an optimal context for the reinitiation of translation. Thus, 5′-PTC triggers NMD in the PKP2, DSG2* and DSC2 genes, whereas it may escape NMD through the reinitiation of the translation in DSP and JUP genes, with no major effects on ACM-related gene expression.  相似文献   

    

Julita Gumna  Maciej Antczak  Ryszard W. Adamiak  Janusz M. Bujnicki  Shi-Jie Chen  Feng Ding  Pritha Ghosh  Jun Li  Sunandan Mukherjee  Chandran Nithin  Katarzyna Pachulska-Wieczorek  Almudena Ponce-Salvatierra  Mariusz Popenda  Joanna Sarzynska  Tomasz Wirecki  Dong Zhang  Sicheng Zhang  Tomasz Zok  Eric Westhof  Zhichao Miao  Marta Szachniuk  Agnieszka Rybarczyk 《International journal of molecular sciences》2022,23(17)

RNA is a unique biomolecule that is involved in a variety of fundamental biological functions, all of which depend solely on its structure and dynamics. Since the experimental determination of crystal RNA structures is laborious, computational 3D structure prediction methods are experiencing an ongoing and thriving development. Such methods can lead to many models; thus, it is necessary to build comparisons and extract common structural motifs for further medical or biological studies. Here, we introduce a computational pipeline dedicated to reference-free high-throughput comparative analysis of 3D RNA structures. We show its application in the RNA-Puzzles challenge, in which five participating groups attempted to predict the three-dimensional structures of 5- and 3-untranslated regions (UTRs) of the SARS-CoV-2 genome. We report the results of this puzzle and discuss the structural motifs obtained from the analysis. All simulated models and tools incorporated into the pipeline are open to scientific and academic use.  相似文献