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  • 1
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    Online Resource
    Downregulation of the Polycomb-Associated Methyltransferase Ezh2 during Maturation of Hippocampal Neurons Is Mediated by MicroRNAs Let-7 and miR-124
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 22 ( 2020-11-11), p. 8472-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 22 ( 2020-11-11), p. 8472-
    Abstract: Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. Previous studies have demonstrated that Enhancer of Zeste Homolog 2 (Ezh2) was differentially expressed during maturation of hippocampal neurons; in immature neurons, Ezh2 was abundantly expressed, whereas in mature neurons the expression Ezh2 was significantly reduced. Here, we report that Ezh2 is downregulated by microRNAs (miRs) that are expressed during the hippocampal maturation process. We show that, in mature hippocampal neurons, lethal-7 (let-7) and microRNA-124 (miR-124) are robustly expressed and can target cognate motifs at the 3′-UTR of the Ezh2 gene sequence to downregulate Ezh2 expression. Together, these data demonstrate that the PRC2 repressive activity during hippocampal maturation is controlled through a post-transcriptional mechanism that mediates Ezh2 downregulation in mature neurons.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21228472
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
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    Online Resource
    Indomethacin Induces Spermidine/Spermine-N1-Acetyltransferase-1 via the Nucleolin-CDK1 Axis and Synergizes with the Polyamine Oxidase Inhibitor Methoctramine in Lung Cancer Cells
    MDPI AG ; 2023
    In:  Biomolecules Vol. 13, No. 9 ( 2023-09-12), p. 1383-
    Details
    In: Biomolecules, MDPI AG, Vol. 13, No. 9 ( 2023-09-12), p. 1383-
    Abstract: Indomethacin is a non-selective NSAID used against pain and inflammation. Although cyclooxygenase (COX) inhibition is considered indomethacin’s primary action mechanism, COX-independent ways are associated with beneficial effects in cancer. In colon cancer cells, the activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) is related to the increase in spermidine/spermine-N1-acetyltransferase-1 (SSAT-1), a key enzyme for polyamine degradation, and related to cell cycle arrest. Indomethacin increases the SSAT-1 levels in lung cancer cells; however, the mechanism relying on the SSAT-1 increase is unclear. Thus, we asked for the influence of the PPAR-γ on the SSAT-1 expression in two lung cancer cell lines: H1299 and A549. We found that the inhibition of PPAR-γ with GW9662 did not revert the increase in SSAT-1 induced by indomethacin. Because the mRNA of SSAT-1 suffers a pre-translation retention step by nucleolin, a nucleolar protein, we explored the relationship between indomethacin and the upstream translation regulators of SSAT-1. We found that indomethacin decreases the nucleolin levels and the cyclin-dependent kinase 1 (CDK1) levels, which phosphorylates nucleolin in mitosis. Overexpression of nucleolin partially reverts the effect of indomethacin over cell viability and SSAT-1 levels. On the other hand, Casein Kinase, known for phosphorylating nucleolin during interphase, is not modified by indomethacin. SSAT-1 exerts its antiproliferative effect by acetylating polyamines, a process reverted by the polyamine oxidase (PAOX). Recently, methoctramine was described as the most specific inhibitor of PAOX. Thus, we asked if methoctramine could increase the effect of indomethacin. We found that, when combined, indomethacin and methoctramine have a synergistic effect against NSCLC cells in vitro. These results suggest that indomethacin increases the SSAT-1 levels by reducing the CDK1-nucleolin regulatory axis, and the PAOX inhibition with methoctramine could improve the antiproliferative effect of indomethacin.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom13091383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2701262-1
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  • 3
    Online Resource
    Online Resource
    Microencapsulation by a Spray Drying Approach to Produce Innovative Probiotics-Based Products Extending the Shelf-Life in Non-Refrigerated Conditions
    MDPI AG ; 2023
    In:  Molecules Vol. 28, No. 2 ( 2023-01-15), p. 860-
    Details
    In: Molecules, MDPI AG, Vol. 28, No. 2 ( 2023-01-15), p. 860-
    Abstract: Recently, there has been a growing interest in producing functional foods containing encapsulated probiotic bacteria due to their positive effects on human health. According to their perceived health benefits, probiotics have been incorporated into a range of dairy products, but the current major challenge is to market new, multicomponent probiotic foods and supplements. Nevertheless, only a few products containing encapsulated probiotic cells can be found as non-refrigerated products. In this work, spray drying technology was investigated in order to produce an innovative nutraceutical formulation based on lactic acid bacteria (LAB), and was able to ensure a good storage stability of probiotics (no less than 109 CFU/cps) in non-refrigerated conditions. Probiotic-loaded microparticles from spray drying experiments were produced under different conditions and compared by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and the enumeration of the number of viable cells in order to identify the formulation exhibiting the most promising characteristics. Results from the dissolution test revealed that the optimized formulation provides a suitable amount of living cells after digestion of microparticles stored for 12 months at room temperature and confirmed that the microencapsulation process by spray drying ensures a good protection of probiotics for nutraceutical purposes.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules28020860
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2008644-1
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  • 4
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    Online Resource
    Effects of Albumin on Survival after a Hepatic Encephalopathy Episode: Randomized Double-Blind Trial and Meta-Analysis
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 21 ( 2021-10-23), p. 4885-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 21 ( 2021-10-23), p. 4885-
    Abstract: No therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode. Methods: (1) A randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient’s data for survival including two clinical trials (BETA and ALFAE) was performed. Results: In total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21–0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02). Conclusions: Repeated doses of albumin might be beneficial for patient’s survival as an add-on therapy after an HE episode, but an adequately powered trial is needed.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10214885
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 5
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    Online Resource
    Neuro-Vulnerability in Energy Metabolism Regulation: A Comprehensive Narrative Review
    MDPI AG ; 2023
    In:  Nutrients Vol. 15, No. 14 ( 2023-07-11), p. 3106-
    Details
    In: Nutrients, MDPI AG, Vol. 15, No. 14 ( 2023-07-11), p. 3106-
    Abstract: This comprehensive narrative review explores the concept of neuro-vulnerability in energy metabolism regulation and its implications for metabolic disorders. The review highlights the complex interactions among the neural, hormonal, and metabolic pathways involved in the regulation of energy metabolism. The key topics discussed include the role of organs, hormones, and neural circuits in maintaining metabolic balance. The review investigates the association between neuro-vulnerability and metabolic disorders, such as obesity, insulin resistance, and eating disorders, considering genetic, epigenetic, and environmental factors that influence neuro-vulnerability and subsequent metabolic dysregulation. Neuroendocrine interactions and the neural regulation of food intake and energy expenditure are examined, with a focus on the impact of neuro-vulnerability on appetite dysregulation and altered energy expenditure. The role of neuroinflammation in metabolic health and neuro-vulnerability is discussed, emphasizing the bidirectional relationship between metabolic dysregulation and neuroinflammatory processes. This review also evaluates the use of neuroimaging techniques in studying neuro-vulnerability and their potential applications in clinical settings. Furthermore, the association between neuro-vulnerability and eating disorders, as well as its contribution to obesity, is examined. Potential therapeutic interventions targeting neuro-vulnerability, including pharmacological treatments and lifestyle modifications, are reviewed. In conclusion, understanding the concept of neuro-vulnerability in energy metabolism regulation is crucial for addressing metabolic disorders. This review provides valuable insights into the underlying neurobiological mechanisms and their implications for metabolic health. Targeting neuro-vulnerability holds promise for developing innovative strategies in the prevention and treatment of metabolic disorders, ultimately improving metabolic health outcomes.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu15143106
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518386-2
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  • 6
    Online Resource
    Online Resource
    SARS-CoV-2 Genome Variations in Viral Shedding of an Immunocompromised Patient with Non-Hodgkin’s Lymphoma
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 2 ( 2023-01-28), p. 377-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 2 ( 2023-01-28), p. 377-
    Abstract: Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is the most transmissible ß-coronavirus in history, affecting all population groups. Immunocompromised patients, particularly cancer patients, have been highlighted as a reservoir to promote accumulation of viral mutations throughout persistent infection. Case presentation. We aimed to describe the clinical course and SARS-CoV-2 mutation profile for 102 days in an immunocompromised patient with non-Hodgkin’s lymphoma and COVID-19. We used RT-qPCR to quantify SARS-CoV-2 viral load over time and whole-virus genome sequencing to identify viral lineage and mutation profile. The patient presented with a persistent infection through 102 days while being treated with cytotoxic chemotherapy for non-Hodgkin’s lymphoma and received targeted therapy for COVID-19 with remdesivir and hyperimmune plasma. All sequenced samples belonged to the BA.1.1 lineage. We detected nine amino acid substitutions in five viral genes (Nucleocapsid, ORF1a, ORF1b, ORF13a, and ORF9b), grouped in two clusters: the first cluster with amino acid substitutions only detected on days 39 and 87 of sample collection, and the second cluster with amino acid substitutions only detected on day 95 of sample collection. The Spike gene remained unchanged in all samples. Viral load was dynamic but consistent with the disease flares. Conclusions. This report shows that the multiple mutations that occur in an immunocompromised patient with persistent COVID-19 could provide information regarding viral evolution and emergence of new SARS-CoV-2 variants.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15020377
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 7
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    Online Resource
    Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 19 ( 2021-09-26), p. 4402-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 19 ( 2021-09-26), p. 4402-
    Abstract: Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered “exposed”. The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2–2.0), urgent surgery (OR: 1.6; 95% CI: 1.2–2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1–1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3–2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97–1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03–2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10194402
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 8
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    41 Cases of Treatment of Cranial Cruciate Ligament Rupture with Porous TTA: Three Years of Follow Up
    MDPI AG ; 2019
    In:  Veterinary Sciences Vol. 6, No. 1 ( 2019-02-20), p. 18-
    Details
    In: Veterinary Sciences, MDPI AG, Vol. 6, No. 1 ( 2019-02-20), p. 18-
    Abstract: Tibial Tuberosity Advancement (TTA) is a surgical technique based on a linear osteotomy that determines a cranial advancement of the tibial tuberosity in patients suffering from cranial cruciate ligament rupture (CCL). The aim is to neutralize the cranial tibial thrust (CTT) and to reach a 90° angle between the patellar tendon and the tibial plateau with a physiological knee extension of 135°. In our study, a Ti6AI4V ELI (Titanium Aluminium Vanadium) titanium scaffold for the Porous TTA, with excellent properties of osteointegration and osteoconduction when subjected to cyclic loading has been adopted. Based on the previous scientific work on an ovine model, the use of this type of porous scaffolds has subverted the previous models. Scaffold production technology is based on direct mechanical manufacturing called Electron Beam Melting (EBM). For this study, 41 dogs, different breeds, medium-large size, weighing between 10 and 80 kg, aged between 1 and 13 years, were enrolled. The inclusion criteria were based on clinical evaluations (different gaits), drawer test and tibial compression, LOAD score (Liverpool Osteoarthritis in Dogs questionnaire), radiographic diagnosis in sedation with a 135° positioning of the joint and baropodometric investigations (Stance Analyzer). The results show that Porous TTA is an excellent method for functional recovery of the knee joint following the partial and total rupture of the CCL.
    Type of Medium: Online Resource
    ISSN: 2306-7381
    URL: Article
    DOI: 10.3390/vetsci6010018
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2768971-2
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  • 9
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    Online Resource
    The Impact of Anorexia Nervosa and the Basis for Non-Pharmacological Interventions
    MDPI AG ; 2023
    In:  Nutrients Vol. 15, No. 11 ( 2023-06-01), p. 2594-
    Details
    In: Nutrients, MDPI AG, Vol. 15, No. 11 ( 2023-06-01), p. 2594-
    Abstract: Anorexia nervosa is a psychiatric disorder with an unknown etiology that is characterized by an individual’s preoccupation with their weight and body structure while denying the severity of their low body weight. Due to the fact that anorexia nervosa is multifaceted and may indicate the coexistence of genetic, social, hormonal, and psychiatric disorders, a description of non-pharmacological interventions can be used to ameliorate or reduce the symptoms of this condition. Consequently, the purpose of the present narrative review is to describe the profile’s context in the anorexic person as well as the support they would require from their family and environment. In addition, it is aimed at examining preventative and non-pharmacological interventions, such as nutritional interventions, physical activity interventions, psychological interventions, psychosocial interventions, and physical therapy interventions. To reach the narrative review aims, a critical review was conducted utilizing both primary sources, such as scientific publications, and secondary sources, such as bibliographic indexes, web pages, and databases. Nutritional interventions include nutritional education and an individualized treatment for each patient, physical activity interventions include allowing patients to perform controlled physical activity, psychological interventions include family therapy and evaluation of the existence of other psychological disorders, psychosocial interventions include management of the relationship between the patient and social media and physical therapy interventions include relaxation massages and exercises to relieve pain. All these non-pharmacological interventions need to be individualized based on each patient’s needs.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu15112594
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518386-2
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  • 10
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    Online Resource
    Pine Pitch Canker (PPC): Pathways of Pathogen Spread and Preventive Measures
    MDPI AG ; 2019
    In:  Forests Vol. 10, No. 12 ( 2019-12-17), p. 1158-
    Details
    In: Forests, MDPI AG, Vol. 10, No. 12 ( 2019-12-17), p. 1158-
    Abstract: Fusarium circinatum (Nirenberg and O’ Donnell) is the causal agent of pine pitch canker (PPC) disease, one of the most devastating forest diseases worldwide. Long-distance spread occurs mainly through the movement of infected seeds whereas at regional level, the movement of seedlings, substrates, or containers may play an important role in fungal dispersal. Invasion of nurseries takes place via infected seeds and further spread can occur by planting contaminated seedlings, especially due to the possibility of infected plants remaining symptomless. Once established, F. circinatum spreads by rain, wind, and insects. The natural spread of the pathogen is limited due to the short dispersal distances of the spores and the fairly short flight distances of disseminating insects. In this review, we summarize the currently known dispersal pathways of the pathogen, discussing both natural and human-assisted processes. With the purpose of understanding how to best intervene in the disease’s development in nurseries and forests, we outline the epidemiology of the pathogen describing the key factors influencing its spread. Preventive measures to control the spread of F. circinatum locally and globally are described with special emphasis on the challenges in implementing them.
    Type of Medium: Online Resource
    ISSN: 1999-4907
    URL: Article
    DOI: 10.3390/f10121158
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527081-3
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