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The use of the same material as anode and cathode in symmetrical solid oxide fuel cells (SFCs) promises notable benefits as easier fabrication, hence lower cost production and resistance to carbon formation upon fuel cracking. Although chromites and chromo-manganites have been proposed as candidate electrode materials for this novel SOFC configuration, demonstrating promising performances, further work is required to develop compositions exhibiting higher efficiencies. In the present work we evaluate the structural evolution from cubic to orthorhombic unit cells with increasing the Fe content and the performance of La4Sr8Ti12-xFexO38-δ (LSTF) phases and compare their response with other symmetrical electrodes. The electrochemical performance is 20% higher when using graded LSTF electrodes than in other perovskite-based systems.La utilización simultánea de un mismo material cerámico como ánodo y cátodo en pilas de combustible de óxido sólido simétricas (SFCs) aporta una serie de beneficios entre los que figura una fabricación más sencilla, reducción de los costes de producción, así como resistencia a la formación de depósitos de carbón por craqueo del combustible. Recientemente, cromitas y cromomanganitas han sido propuestos como materiales capaces de adoptar esta novedosa configuración SOFC y, si bien los resultados obtenidos son prometedores, se requiere de una mayor investigación para el desarrollo de nuevas composiciones que presenten eficiencias más elevadas. En el presente trabajo, se evalúan la evolución de la estructura desde celdas cúbicas a ortorrómbicas al aumentar el contenido en Fe y las prestaciones del sistema La4Sr8Ti12-xFexO38-δ (LSTF) y se compara su respuesta con otros electrodos simétricos, observándose que el rendimiento es hasta un 20% mayor en el caso de emplear electrodos LSTF que en otros sistemas basados en perovskitas.

The spread of bacterial resistance has become a significant public health concern, resulting in increased healthcare costs, mortality, and morbidity. Phytochemicals such as Eugenol, the major component of Indian clove and cinnamon essential oils, have attracted attention due to their antimicrobial potential. Thus, this systematic review aims to analyze the existing literature on the antibacterial potential of Eugenol concerning its activity against biofilms, bacterial communication systems (quorum sensing - QS), and associated virulence factors. For this, four databases were systematically searched to retrieve articles published between 2010 and 2023. Fourteen articles were selected based on eligibility criteria and the evaluation of antibacterial activity through minimum inhibitory concentration (MIC) assays, biofilm studies, and assessment of virulence factors. The results revealed that Eugenol has the potential to act as an antimicrobial, antibiofilm, anti-virulence, and anti-QS agent against a variety of bacterial strains associated with chronic, dental, and foodborne infections, including resistant strains, particularly those in the ESKAPE group (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and clinical isolates. Furthermore, Eugenol effectively targets key genes involved in bacterial virulence regulation, biofilm, and QS, as supported by data from multiple assays and research techniques. This review suggests Eugenol's antibacterial activity against biofilm and virulence factors likely stems from its influence on different QS systems. Finally, Eugenol holds promise as a potential candidate for combating resistant bacterial infections, serving as an anti-biofilm agent in medical devices and hospital surfaces, as well as in the food industry, as a toothpaste additive, and as a molecule for the development of new therapeutic agents with the potential to inhibit bacterial virulence, QS systems and avoiding bacterial resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Context: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients., Methods: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Search for new clinical biomarkers targets in prostate cancer (PC) is urgent. Telomeres might be one of these targets. Telomeres are the extremities of linear chromosomes, essential for genome stability and control of cell divisions. Telomere homeostasis relies on the proper functioning of shelterin and CST complexes. Telomeric dysfunction and abnormal expression of its components are reported in most cancers and are associated with PC. Despite this, there are only a few studies about the expression of the main telomere complexes and their relationship with PC progression. We aimed to evaluate the role of shelterin (POT1, TRF2, TPP1, TIN2, and RAP1) and CST (CTC1, STN1, and TEN1) genes and telomere length in the progression of PC., Methods: We evaluated genetic alterations of shelterin and CST by bioinformatics in samples of localized (n = 499) and metastatic castration-resistant PC (n = 444). We also analyzed the expression of the genes using TCGA (localized PC n = 497 and control n = 152) and experimental approaches, with surgical specimens (localized PC n = 81 and BPH n = 10) and metastatic cell lines (LNCaP, DU145, PC3 and PNT2 as control) by real-time PCR. Real-time PCR also determined the telomere length in the same experimental samples. All acquired data were associated with clinical parameters., Results: Genetic alterations are uncommon in PC, but POT1, TIN2, and TEN1 showed significantly more amplifications in the metastatic cancer. Except for CTC1 and TEN1, which are differentially expressed in localized PC samples, we did not detect an expression pattern relative to control and cell lines. Nevertheless, except for TEN1, the upregulation of all genes is associated with a worse prognosis in localized PC. We also found that increased telomere length is associated with disease aggressiveness in localized PC., Conclusion: The upregulation of shelterin and CST genes creates an environment that favors telomere elongation, giving selective advantages for localized PC cells to progress to more aggressive stages of the disease., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The use of angiography in postmortem CT angiography (PMCTA) has several advantages. In adults, femoral vascular access is well established. Due to the small and specific anatomy in fetuses and infants, the technique has to be adapted, especially regarding the vascular access. The aim of this study was to evaluate vascular access for pediatric PMCTA (pedPMCTA)., Materials and Methods: Ten pedPMCTAs were performed in stillbirths, babies, and one toddler. A femoral approach by cannulation of the femoral artery and vein, an umbilical approach by cannulation of the umbilical vessels, and an intraosseous approach by an intraosseous needle were evaluated by handling and resulting imaging., Results: The insertion of a cannula with a size of 18-20 G in the femoral vessels was possible in babies. An umbilical access with peripheral venous cannulas with a size of 14-20 G was feasible in stillbirths and newborns. An intraosseous access is advisable as equal alternative to umbilical and in cases where a femoral access is not possible. The most significant problem with the vascular access is the extravasation of contrast media, but this can be reduced significantly with practice., Conclusion: When performing pedPMCTA, an umbilical vascular access is recommended if an umbilical cord with open vessels is still present. Otherwise, a bone marrow access should be preferred in the presence of an arteriovenous shunt or if only the venous system needs to be shown. If that is not the case, the femoral access with the possibility to separate venous and arterial scan should be used., (© 2023. The Author(s).)

Despite their biological importance, the role of stem cells in human aging remains to be elucidated. In this work, we applied a machine learning methodology to GTEx transcriptome data and assigned stemness scores to 17,382 healthy samples from 30 human tissues aged between 20 and 79 years. We found that ~60% of the studied tissues exhibit a significant negative correlation between the subject's age and stemness score. The only significant exception was the uterus, where we observed an increased stemness with age. Moreover, we observed that stemness is positively correlated with cell proliferation and negatively correlated with cellular senescence. Finally, we also observed a trend that hematopoietic stem cells derived from older individuals might have higher stemness scores. In conclusion, we assigned stemness scores to human samples and show evidence of a pan-tissue loss of stemness during human aging, which adds weight to the idea that stem cell deterioration may contribute to human aging.

Bladder carcinoma (BC) is the tenth most frequent malignancy worldwide, with high morbidity and mortality rates. Despite recent treatment advances, high-grade BC and muscle-invasive BC present with significant progression and recurrence rates, urging the need for alternative treatments. The microRNA-21 (miR-21) has superexpression in many malignancies and is associated with cellular invasion and progression. One of its mechanisms of action is the regulation of RECK, a tumor suppressor gene responsible for inhibiting metalloproteinases, including MMP9. In a high-grade urothelial cancer cell line, we aimed to assess if miR-21 downregulation would promote RECK expression and decrease MMP9 expression. We also evaluated cellular migration and proliferation potential by inhibition of this pathway. In a T24 cell line, we inhibited miR-21 expression by transfection of a specific microRNA inhibitor (anti-miR-21). There were also control and scramble groups, the last with a negative microRNA transfected. After the procedure, we performed a genetic expression analysis of miR-21, RECK, and MMP9 through qPCR. Migration, proliferation, and protein expression were evaluated via wound healing assay, colony formation assay, flow cytometry, and immunofluorescence.After anti-miR-21 transfection, miR-21 expression decreased with RECK upregulation and MMP9 downregulation. The immunofluorescence assay showed a significant increase in RECK protein expression (p < 0.0001) and a decrease in MMP9 protein expression (p = 0.0101). The anti-miR-21 transfection significantly reduced cellular migration in the wound healing assay (p < 0.0001). Furthermore, in the colony formation assay, the anti-miR-21 group demonstrated reduced cellular proliferation (p = 0.0008), also revealed in the cell cycle analysis by flow cytometry (p = 0.0038). Our results corroborate the hypothesis that miR-21 is associated with BC cellular migration and proliferation, revealing its potential as a new effective treatment for this pathology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression., Methods: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints., Results: The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p < 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p < 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p < 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p < 0.0005), with a shorter time-to-recurrence in the super-expression group (p < 0.0001)., Conclusion: Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools., (© 2024. The Author(s).)

This study evaluated litter performance, behavioral and physiological parameters, and milk characteristics of sows submitted to different thermal environments. Fifty sows were distributed in a completely randomized design with two treatments: an evaporative cooling system (ECS) and a conventional system (CS). Sow and its litter were characterized as an experimental unit. The animals were weighed at equalization and weaning. Feed intake, milk production, and bromatological characteristics of milk were measured; the sows respiratory rate, rectal, and surface temperature were monitored. Litter uniformity was determined at equalization and weaning. Behaviors of the sows and litters were monitored for 24 h on the 7th and 15th day of lactation. Temperature and relative humidity inside the maternity was 25.00 to 28.00 °C and 26.00 to 32.55 °C and 30.00 to 70.00% and 70.00 to 88.00%, respectively, considering ECS and CS. Nutritional quality of the milk remained stable during lactation in both systems evaluated. ECS improved the average weight of the piglets, weaning weight, and daily milk production by 0.038, 0.699, and 2.31 kg/day, respectively. Sows housed in the ECS had a reduction in physiological parameters and, increase in inactive alert behavior (1.79 percentage points) and breastfeeding behavior. Piglets showed a decrease of 2.43% in the range of feedings at night and 0.15% during the day. ECS provided better comfort to the sows at the expense of the CS and, consequently, better litter performance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/)., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx., Results: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns., Conclusion: We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis., (© 2023. The Author(s).)

Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.

Glycolytic overload in diabetes causes large accumulation of the highly reactive dicarbonyl compound methylglyoxal (MGO) and overproduction of advanced glycation end products (AGEs), which interact with their receptors (RAGE), leading to diabetes-associated macrovascular complications. The bladder is an organ that stays most in contact with dicarbonyl species, but little is known about the importance of the MGO-AGEs-RAGE pathway to diabetes-associated bladder dysfunction. Here, we aimed to investigate the role of the MGO-AGEs-RAGE pathway in bladder dysfunction of diabetic male and female ob / ob mice compared with wild-type (WT) lean mice. Diabetic ob / ob mice were treated with the AGE breaker alagebrium (ALT-711, 1 mg/kg) for 8 wk in drinking water. Compared with WT animals, male and female ob / ob mice showed marked hyperglycemia and insulin resistance, whereas fluid intake remained unaltered. Levels of total AGEs, MGO-derived hydroimidazolone 1, and RAGE in bladder tissues, as well as fluorescent AGEs in serum, were significantly elevated in ob / ob mice of either sex. Collagen content was also markedly elevated in the bladders of ob / ob mice. Void spot assays in filter paper in conscious mice revealed significant increases in total void volume and volume per void in ob / ob mice with no alterations of spot number. Treatment with ALT-711 significantly reduced the levels of MGO, AGEs, RAGE, and collagen content in ob / ob mice. In addition, ALT-711 treatment normalized the volume per void and increased the number of spots in ob / ob mice. Activation of AGEs-RAGE pathways by MGO in the bladder wall may contribute to the pathogenesis of diabetes-associated bladder dysfunction. NEW & NOTEWORTHY The involvement of methylglyoxal (MGO) and advanced glycation end products (AGEs) in bladder dysfunction of diabetic ob/ob mice treated with the AGE breaker ALT-711 was investigated here. Diabetic mice exhibited high levels of MGO, AGEs, receptor for AGEs (RAGE), and collagen in serum and/or bladder tissues along with increased volume per void, all of which were reduced by ALT-711. Activation of the MGO-AGEs-RAGE pathway in the bladder wall contributes to the pathogenesis of diabetes-associated bladder dysfunction.

Background: Previously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia., Methods and Results: In vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 µg/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation., Conclusion: Our results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 μg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Purpose: To evaluate if the density of interstitial cells of Cajal (ICC) in the ureteropelvic junction (UPJ) influences the outcomes of pyeloplasty in adults., Methods: Twenty-three patients with the diagnosis of ureteropelvic junction obstruction (UPJO) that underwent laparoscopic dismembered pyeloplasty were included. ICC density was measured using immunohistochemistry reaction for c-KIT expression in the resected UPJ segment. Pyeloplasty outcome was evaluated by patient self-report pain, urinary outflow using DTPA renogram and hydronephrosis assessment using ultrasound (US) at 12 months of follow-up. A logistic regression analysis was performed to assess the association of pyeloplasty outcomes and ICC density., Results: Low, moderate, and high ICC density were present in 17.4%, 30.4%, and 52.2% of the patients, respectively. Complete pain resolution was observed in 100%, 85.7%, and 75% of patients with low, moderate and high ICC density, respectively ( p  = 0.791). DTPA renogram improved in 75%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively ( p  = 0.739). Hydronephrosis improved in 25%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively ( p  = 0.032)., Conclusions: Patients with high ICC density have a significant amelioration of hydronephrosis after pyeloplasty. However, ICC density is not associated with functional outcomes.

Background/aims: Cholesterol modulates intratumoral androgenic signaling in prostate cancer; however, the molecular mechanisms underlying these changes in castration-resistant prostate cancer (CRPC) are not fully elucidated. Herein, we investigated the effect of cholesterol on androgen receptor (AR) coactivators expression and tumorigenesis in vitro and in vivo., Methods: Herein, we monitored the expression of AR coactivators (SRC-1, 2, 3 and PCAF) genes in PC-3 cells exposed to 2µg/mL of cholesterol for 8 hours by qPCR. We also performed cell migration at 0, 8, 24, 48 and 72h and flow cytometry assays (viability, apoptosis, and cell cycle) after a 24h exposure. Immunofluorescence assay was performed to evaluate the protein expression of the AR coactivators. Additionally, in vivo experiments were conducted using 22 male NOD/SCID mice. Mice were fed a standard (Control) or hypercholesterolemic (HCOL) diet for 21 days and then subcutaneously implanted with PC-3 cells. The tumor volume was calculated every two days, and after four weeks, the tumors were resected, weighed, and the serum lipid profile was measured. We also measured the intratumoral lipid profile and AR coactivators gene and protein expression by qPCR and Western Blot, respectively. Intratumor testosterone and dihydrotestosterone (DHT) concentrations were determined using ELISA., Results: Cholesterol up-regulated the gene expression of coactivators SRC-1, SRC-2, SRC-3
and PCAF, increasing AR expression in PC-3 cells. Next, cholesterol-supplemented PC-3 cells exhibited increased cell migration and altered cell cycle phases, leading to changes in proliferation and reduced apoptosis. We found that SRC-1, SRC-2, SRC-3 and PCAF proteins co-localized in the nucleus of cholesterol-supplemented cells and co-associate with AR. In the in vivo model, the hypercholesterolemic (HCOL) group displayed higher serum total and intratumoral cholesterol levels, increased testosterone and dihydrotestosterone concentrations, and up-regulated AR coactivator expression. The tumor volume of the HCOL group was significantly higher than the control group., Conclusion: Our findings revealed that increased nuclear translocation of the coactivators leads to up-regulated AR gene and protein expression, potentially influencing tumor progression. Studies targeting cholesterol-modulated changes in AR coactivator expression may provide insights into the molecular mechanisms associated with the CRPC phenotype., Competing Interests: The authors declare that no conflict of interests exists., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

In this systematic review, we aimed to identify the impact of the COVID-19 pandemic on children/adolescents with a diagnosis of autism spectrum disorder (ASD). The protocol was registered on PROSPERO CRD42021255848. Articles were selected from PubMed, Embase, and LILACS according to these characteristics: patients from zero to 18 years old, exposed to the COVID-19 pandemic, impact on social communication/interaction and restricted/repetitive behavior domains. The Newcastle-Ottawa Scale was used to assess methodological quality and the risk of bias. Of the 351 articles initially identified, 26 were finally included with information on 8,610 patients. Although the studies were heterogeneous, they indicated that the pandemic-related issues experienced by patients with ASD were mostly manifested in their behavior and sleep patterns., Supplementary Information: The online version contains supplementary material available at 10.1007/s40489-022-00344-4., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Peyronie's disease (PD) is characterized by the formation of fibrous plaque in tunica albuginea, causing several problems in patients. The etiology of this disease is not fully understood, and there are few effective treatments. To better understand the molecular pathways of PD, we studied miR-29b, a microRNA that could be involved with this illness. MicroRNAs are endogenous molecules that act by inhibiting messenger RNA. MiR-29b regulates 11 of 20 collagen genes and the TGF-β1 gene, which are related to PD progression., Methods: We compared miR-29b expression in 11 patients with PD and 14 patients without PD (control group). For the patients with PD, we utilized samples from the fibrous plaque ( n = 9), from the tunica albuginea ( n = 11), and from the corpus cavernosum ( n = 8). For the control group, we utilized samples from the tunica albuginea ( n = 14) and from the corpus cavernosum ( n = 10). MiR-29b expression was determined by q-PCR., Results: We found a downregulation of miR-29b in the fibrous plaque, tunica albuginea and corpus cavernosum of patients with PD in comparison with the control group ( p = 0.0484, p = 0.0025, and p = 0.0016, respectively)., Conclusion: Although our study has a small sample, we showed for the first time an evidence that the downregulation of miR-29b is associated with PD.

Postacute COVID-19 has become a relevant public health problem, and radiological and pulmonary function tests are tools that help physicians in decision-making. The objectives of this study are to characterize the findings and patterns on a chest radiograph (CXR) and computed tomography (CT) that are most important in the postacute phase and to evaluate how these changes correlate with clinical data, spirometry, and impulse oscillometry (IOS). This was a retrospective study of 29 patients who underwent CXR, CT, spirometry, and IOS. The inclusion criteria were age >18 years and persistent respiratory symptoms after four weeks. The exclusion criteria were radiological exams with low technical quality and non-COVID-19 acute lung diseases. The inferential analysis was carried out with the chi-square ( χ 2 ) or Fisher's exact test to evaluate the interrelationships between the clinical and COVID-19 variables according to spirometry, IOS, CT, and CXR. In our sample, 19 patients were women (65.5%). The predominance of abnormal spirometry was associated with CT's moderate/severe degree of involvement ( p  = 0.017; 69.2%, CI 95%: 44.1%-94.3%). There was no significant association between IOS and tomographic and radiographic parameters. A significant association was found between the classifications of the moderate/severe and normal/mild patterns on CT and CXRs ( p  = 0.003; 93.3%, CI 95%: 77.8%-100%). Patients with moderate/severe impairment on CXR were associated with a higher frequency of hospitalization ( p  = 0.033; 77.8%, CI 95%: 58.6%-97.0%) and had significantly more moderate/severe classifications in the acute phase than the subgroup with normal/mild impairment on CXR ( p  = 0.017; 88.9%, CI 95%: 74.4%-100%). In conclusion, the results of this study show that CXR is a relevant examination and may be used to detect nonspecific alterations during the follow-up of post-COVID-19 patients. Small airway disease is an important finding in postacute COVID-19 syndrome, and we postulate a connection between this pattern and the persistently low-level inflammatory state of the lung., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Roberto Mogami et al.)

Telomere dysfunction is one of the hallmarks of cancer, which puts telomere-associated genes in a prominent position in oncology. The CTC1-STN1-TEN1 (CST) complex is vital for telomere maintenance and participates in several steps of DNA metabolism, such as repair and replication, essential functions for malignant cells. Despite this, little is known about these genes in cancer biology. Here, using bioinformatics tools, we performed a study in 33 cancer types and over 10,000 TCGA samples analyzing the role of the CST complex in cancer. We obtained the somatic landscape and gene expression patterns of each of the subunits of the complex studied. Furthermore, we show that CST is important for genetic stability and nucleic acid metabolism in cancer. We identify possible interactors, transcription factors, and microRNAs associated with CST and two drugs that may disrupt their pathways. In addition, we show that CST gene expression is associated with cancer survival and recurrence in several tumor types. Finally, we show negative and positive correlations between immune checkpoint genes and CST in different types of cancer. With this work, we corroborate the importance of these genes in cancer biology and open perspectives for their use in other works in the field., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Several studies have already shown that changes in the AR gene may be associated with a more aggressive disease phenotype and even castration-resistant prostate cancer. Thus, we investigated cytogenetic and molecular alterations linked to AR., Materials and Methods: To evaluate AR methylation, we performed a cytogenetic-molecular analysis using fluorescence in situ hybridization that uses specific probes for the AR gene (Xq11.12) and the X chromosome centromere. For AR activity, we performed a qualitative analysis of human androgen receptor activity. To analyze the expression of AR in PC3 and LNCaP cell lines, we used qPCR assays., Results: In the qPCR assay, we found downregulation of AR in the PC3 cell line compared with the LNCaP. We found the presence of X chromosome polysomy in PC-3 and LNCaP cell lines by FISH assay. In the HUMARA-Q assay, we found two X chromosomes/cell and the activity of both AR in the PC-3 cell line. In LNCaP cells, we found two X chromosomes/cell and methylation of only one AR., Conclusion: Castration-resistant prostate cancer phenotype represents a significant challenge in the setting of urological management. The X chromosomes and AR-linked alterations may contribute to a better understanding of the disease. However, further studies should be performed in an attempt to elucidate as much as possible the role of AR in the castration-resistant prostate cancer phenotype., (Copyright © 2021 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Prostate cancer is the most frequent malignancy affecting men worldwide. Due to the low sensitivity and specificity of the prostate-specific antigen test and the digital rectal exam as screening modalities, several alternatives are being studied. This study aimed to evaluate the application of MMP-9 and its regulators (TIMP-1, RECK, and miR-338-3p) as diagnostic and prognostic indicators of prostate cancer. A total of 134 randomly selected patients under investigation for prostate cancer submitted to a transrectal ultrasound-guided prostate biopsy were enrolled in the study; of these, 61 were positive for the disease (cases), and 73 were negative (control group). The tissue samples were further analyzed by gene and miR-338-3p expression analysis using qRT-PCR (one randomly selected fragment of each patient). Approximately 58% of the patients with prostate cancer presented MMP9 upregulation, while 73%, 65%, and 69% downregulated IMP-1, RECK, and miR-338-3p, respectively. MiR-338-3p was expressed at lower levels in patients with PSA concentrations exceeding 20 ng/mL (p=0.045) and abnormal DRE (p=0.006), while the RECK was more expressed in patients with abnormal DRE (p=0.01). We found that most patients with prostate cancer overexpressed MMP-9; on the other hand, most of them underexpressed TIMP-1, RECK, and miR-338-3p. MiR-338-3p presented as a possible predictor of poor prognosis. Further studies are warranted to evaluate these biomarkers as prognosis factors better., Competing Interests: The authors declare that they have no competing interests.

Background: Telomere dysfunction is one of the hallmarks of cancer and is crucial to prostate carcinogenesis. TERF1 is a gene essential to telomere maintenance, and its dysfunction has already been associates with several cancers. TERF1 is a target of miR-155, and this microRNA can inhibit its expression and promotes carcinogenesis in breast cancer. We aim to analyze TERF1, in gene and mRNA level, involvement in prostate cancer progression., Results: Alterations in TERF1 DNA were evaluated using datasets of primary tumor and castration-resistant tumors (CRPC) deposited in cBioportal. The expression of TERF1 mRNA levels was assessed utilizing TCGA datasets, clinical specimens, and metastatic prostate cancer cell lines (LNCaP, DU145, and PC3). Six percent of localized prostate cancer presents alterations in TERF1 (the majority of that was amplifications). In the CRPC cohort, 26% of samples had TERF1 amplification. Patients with TERF1 alterations had the worst overall survival only on localized cancer cohort (p = 0.0027). In the TCGA cohort, mRNA levels of TERF1 were downregulated in comparison with normal tissue (p = 0.0013) and upregulated in tumors that invade lymph nodes (p = 0.0059). The upregulation of TERF1 is also associated with worst overall survival (p = 0.0028) and disease-free survival (p = 0.0023). There is a positive correlation between TERF1 and androgen receptor expression in cancer tissue (r = 0.53, p < 0.00001) but not on normal tissue (r = - 0.16, p = 0.12). In the clinical specimens, there is no detectable expression of TERF1 and upregulation of miR-155 (p = 0.0348). In cell lines, TERF1 expression was higher in LNCaP and was progressively lower in DU145 and PC3 (p = 0.0327) with no differences in miR-155 expression., Conclusion: Amplification/upregulation of TERF1 was associated with the worst prognostic in localized prostate cancer. Our results corroborate that miR-155 regulates TERF1 expression in prostate cancer. TERF1 has the potential to become a biomarker in prostate cancer., (© 2021. The Author(s).)

The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors.)

The new identified protein telomeric zinc-finger associated protein (TZAP) is a negative regulator of telomere length. Since telomere length and telomere maintenance mechanisms are essential to cancer progression, TZAP is considered a new player in cancer biology. Here we aimed to analyze TZAP using the Cancer Genome Atlas data in a Pan-Cancer approach. We gathering data from TCGA Pan-Cancer studies utilizing cBioPortal, GEPIA and UALCAN. In total we analyzed 33 types of cancer (n=9664) and their respective controls (n=711). TZAP is transcribed in all cancers but less than 5% of all tumors show any somatic changes. TZAP was downregulated in kidney chromophobe carcinoma, and upregulated in esophageal cancer, head and neck squamous cell carcinomas, kidney renal clear cell carcinoma and in liver hepatocellular carcinoma. Globally, TZAP expression is related to favorable prognosis, associated to better overall and disease-free survival. Looking to specific tumors, TZAP expression has a dual behavior. Its downregulation is associated with poor prognosis in cervical squamous cell carcinoma, in kidney renal clear cell carcinoma, kidney papillary cell carcinoma, lung adenocarcinoma and pancreas adenocarcinoma. On the contrary, in adrenocortical carcinoma, colon and rectal cancer, brain lower grade glioma and prostate adenocarcinoma the upregulation of TZAP is related with poor prognosis. TZAP expression has a positive correlation with TRF1 and TRF2 in normal tissue but not in cancer. Our analyses indicate that TZAP has an important role in oncology and may be considered as a potential biomarker., Competing Interests: The authors declare that they have no conflict of interest.

COVID-19 represents a public health emergency, whose mechanism of which is not fully understood. It is speculated that microRNAs may play a crucial role in host cells after infection by SARS-CoV-2. Thus, our study aimed to analyze the expression of miR-200c-3p in saliva samples from patients with COVID-19. One handred eleven samples from patients with COVID-19 were divided into 4 groups. Group I: 39 patients negative for Covid-19; Group II: 37 positive and symptomatic patients, with no indication of hospitalization; Group III: 21 patients with respiratory disorders (hospitalized); Group IV: 14 patients with severe conditions (oxygen therapy). The expression levels of miR-200c-3p were determined using qPCR. We found greater expression of miR-200c-3p in patients in group IV ( p <0.0001), and also verified that patients aged ≥42 years had a higher expression of this miR ( p =0.013). Logistic regression analysis revealed that the expression of miR-200c-3p and systemic arterial hypertension are factors independently associated with patients in group IV ( p <0.0001). Our results suggest that miR-200c-3p is a predictor of severity independent of COVID-19 risk factors, which could represent a way of screening patients affected by SARS-CoV-2., Competing Interests: The authors declare that they have no conflict of interests.

Background and Objectives: To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD)., Methods: The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described., Results: Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection., Discussion: Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

To compare tissue trauma between Retropubic Radical Prostatectomy and Robotically Assisted Laparoscopic Radical Prostatectomy by inflammatory mediators. Serum samples from 40 patients submitted to RALP and 20 patients submitted to RRP were withdrawn at four different time points. The cytokines IL-4, IL-8, IL-6, IL-1B, IL-10 and TNF-α were detected using ELISA/Multiplex assays and xMAP-Luminex®. With both techniques, IL-10 and IL-6 were higher in T4 than in T1-T3 (p = 0.001). IL-10 and IL-6 were higher in T4 in open surgery than in robotic surgery (p = 0.000 and p = 0.001, respectively). Compared with both groups, IL-6 and IL-10 were higher in T4 in open surgery than in robotic surgery. Thus, we can postulate that RALP causes less tissue trauma than classical RRP, as indicated by the more limited increase in inflammatory mediators such as IL-6 and IL-10.

Topical ophthalmic antibiotics show low efficacy due to the well-known physiological defense mechanisms of the eye, which prevents the penetration of exogenous substances. Here, we aimed to incorporate besifloxacin into liposomes containing amines as positively charged additives and to evaluate the influence of this charge on drug delivery in two situations: (i) iontophoretic and (ii) passive treatments. Hypothesis are (i) charge might enhance the electromigration component upon current application improving penetration efficiency for a burst drug delivery, and (ii) positive charge might prolong formulation residence time, hence drug penetration. Liposomes elaborated with phosphatidylcholine (LP PC) or phosphatidylcholine and spermine (LP PC: SPM) were stable under storage at 6 ºC for 30 days, showed mucoadhesive characteristics, and were non-irritant, according to HET-CAM tests. Electron paramagnetic resonance spectroscopy measurements showed that neither the drug nor spermine incorporations produced evident alterations in the fluidity of the liposome's membranes, which retained their structural stability even under iontophoretic conditions. Mean diameter and zeta potential were 177.2 ± 2.7 nm and - 5.7 ± 0.3 mV, respectively, for LP PC; and 175.4 ± 1.9 nm and + 19.5 ± 1.0 mV, respectively, for LP PC:SPM. The minimal inhibitory concentration (MIC) and the minimal bactericide concentration (MBC) of the liposomes for P. aeruginosa showed values lower than the commercial formulation (Besivance). Nevertheless, both formulations presented a similar increase in permeability upon the electric current application. Hence, liposome charge incorporation did not prove to be additionally advantageous for iontophoretic therapy. Passive drug penetration was evaluated through a novel in vitro ocular model that simulates the lacrimal flow and challenges the formulation resistance in the passive delivery situation. As expected, LP PC: SPM showed higher permeation than the control (Besivance). In conclusion, besifloxacin incorporation into positively charged liposomes improved passive topical delivery and can be a good strategy to improve topical ophthalmic treatments.

Background: Telomeres are chromosome end structures important in the maintenance of genome homeostasis. They are replenished by the action of telomerase and associated proteins, such as the OB (oligonucleotide/oligosaccharide-binding)-fold containing telomere-end binding proteins (TEBP) which plays an essential role in telomere maintenance and protection. The nature of TEBPs is well known in higher and some primitive eukaryotes, but it remains undetermined in trypanosomatids. Previous in silico searches have shown that there are no homologs of the classical TEPBs in trypanosomatids, including Leishmania sp. However, Replication Protein A subunit 1 (RPA-1), an OB-fold containing DNA-binding protein, was found co-localized with trypanosomatids telomeres and showed a high preference for the telomeric G-rich strand., Methods and Results: We predicted the absence of structural homologs of OB-fold containing TEBPs in the Leishmania sp. genome using structural comparisons. We demonstrated by molecular docking that the ssDNA binding mode of LaRPA-1 shares features with the higher eukaryotes POT1 and RPA-1 crystal structures ssDNA binding mode. Using fluorescence spectroscopy, protein-DNA interaction assays, and FRET, we respectively show that LaRPA-1 shares some telomeric functions with the classical TEBPs since it can bind at least one telomeric repeat, protect the telomeric G-rich DNA from 3'-5' Exonuclease I digestion, and unfold telomeric G-quadruplex., Conclusions: Our results suggest that RPA-1 emerges as a TEBP in trypanosomatids, and in this context, we present two possible evolutionary landscapes of trypanosomatids RPA-1 that could reflect upon the evolution of OB-fold containing TEBPs from all eukaryotes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Problem: Gut dysbiosis is caused by several factors, including the use of antibiotics. Since intestinal dysbiosis is associated with a wide range of immunopathological and reproductive conditions, the main goal of this study was to evaluate amoxicillin-induced gut dysbiosis and its influence on the oestrous cycle in mice., Method of Study: Mice were treated with amoxicillin or PBS, and faecal microbiota was evaluated by 16S rDNA metagenomic sequencing. The oestrous cycle was evaluated by vaginal cytology, vaginal opening and flow cytometry. After the induction of gut dysbiosis, the ovaries and the caecum were analysed to differential expression of IL-1β and IL-10 genes and histological analysis., Results: Amoxicillin-treated mice presented differing bacterial groups in the faecal microbiota when compared to the PBS-treated group indicating that amoxicillin treatment-induced gut dysbiosis and they gained weight. The vaginal cytology analysis showed that amoxicillin-induced gut dysbiosis decreased the number of cells but increased the relative number of leucocytes and altered the oestrous cycle. IL-1β was shown to be upregulated in the caecum and in the ovary of the dysbiotic mice. On the other hand, IL-10 expression was shown to be diminished in both organs of the dysbiotic mice. The oocyte area from dysbiotic group presented lower than non-dysbiotic mice with increasing thickness of the pellucid zone. The follicular teak from dysbiotic mice showed lower thickness than non-dysbiotic mice., Conclusion: The results indicate that amoxicillin induces gut dysbiosis and influences the oestrous cycle and the inflammatory status of the ovary and the caecum., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17-11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.

Objective: To identify self-care actions for the maintenance of arteriovenous fistula of renal patients., Method: An integrative review study was conducted and literature were searched in Medline/PubMed, Scopus, CINAHL, LILACS, BDENF and SciELO Library databases using the descriptors chronic renal insufficiency, arteriovenous fistula, self-care, and knowledge. The inclusion criteria were that the documents be written in Portuguese, English, and Spanish, full text available, published in the last five years, and that they address the research question. Reflection articles, theses, dissertations, editorials of non-scientific journals, and research studies that did not follow the necessary methodological rigor were excluded. Data were analyzed with the IRAMUTEQ software., Results: Fifteen articles were selected and comprised the final sample. Seven classes of self-care actions emerged from the text segments analysis and grouped into three categories: 1) Self-care actions that maintain the arteriovenous fistula; 2) Self-care actions for the prevention and the monitoring of complications with arteriovenous fistula; 3) Self-care actions directed at the perioperative period of arteriovenous fistula preparation., Conclusion: The results allowed us to identify important care for the maintenance of arteriovenous fistula functionality. The self-care actions identified in this study can guide a nursing care policy for implementation with protocols that help identify problems related to self-care actions and, thus, subsidize the development of actions aimed at the renal patient. However, more studies with high levels of evidence that identify self-care actions with arteriovenous fistula and the factors involved in its implementation are needed., Competing Interests: No conflict of interest is declared by the authors., (© 2020 The authors. Published by Elsevier B.V. on behalf of the Chinese Nursing Association.)

Objective: To characterize the spectrum of brain damages presented in children affected by Congenital Zika Syndrome (CZS), verify the existence of a co-occurrence pattern of these damages and discuss possible implications for the neuropsychological development., Methods: Descriptive, quantitative, individualized, and cross-sectional study using secondary sources. We selected 136 children with CZS from the database of the Center of Strategic Information on Health Vigilance of the Municipal Office of Salvador, Brazil. We conducted descriptive and multiple correspondence analyses., Results: Among the set of analyzed variables, microcephaly (51.5%), ventriculomegaly (57.4%), and brain calcifications (77.2%) were identified as the most frequent. The multiple correspondence analysis showed that the combination of these three variables (32.4%) was what better represented the spectrum of brain damages in the Central Nervous System., Interpretation: Damage in the sensory-motor, cognitive and language development, as well as neurodevelopmental disorders, are described in the literature as impairments associated, either isolated or combined, with these damages, and it is worth highlighting that, in combined brain damages, impairments tend to be more severe. The findings of this study may contribute to understanding the repercussions of CZS on the neuropsychological development of children affected by the epidemic., (© 2020 International Society for Developmental Neuroscience.)

Strategies to enhance corneal penetration of voriconazole (VOR) could improve the treatment of fungal keratitis. Here, we evaluated the use of iontophoresis for ocular VOR delivery from either: (i) a cyclodextrin inclusion complex (CD VOR), (ii) a liposome (LP VOR), and (iii) a chitosan-coated liposome (LP VOR CS). LP VOR CS presented mean diameter of 139.2 ± 1.3 nm and zeta potential equal to + 3.3 ± 1.5 mV compared to 134.6 ± 1.7 and -8.2 ± 3.0 mV of LP VOR, which, together with mucin mucoadhesion study, confirmed chitosan-coating. Both drug and liposomal formulations were stable under the influence of an applied electric current. Interestingly, in vitro studies in Candida glabrata culture indicated a decrease in VOR MIC values following iontophoresis (from 0.28 to 0.14 µg/mL). Iontophoresis enhanced drug penetration into the cornea. After 10 min of a 2 mA/cm 2 applied current, corneal retained amounts were 45.4 ± 11.2, 30.4 ± 2.1 and 30.6 ± 2.9 µg/cm 2 for, respectively, CD VOR, LP VOR, and LP VOR CS. In conclusion, iontophoresis increases drug potency and enhances drug penetration into the cornea, showing potential to be used as "an emergency burst delivery approach"., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lipid rafts are ordered membrane domains, which provide an environment for the proteins participating in signal transduction. Perifosine is an alkylphospholipid (APL) that inhibits the AKT pathway, cytotoxic to neoplastic cells. We have shown that the lipid raft adaptor protein NTAL is a target of APLs in leukemic cells. Using human mantle cell lymphoma (MCL) Granta-519 cell line we showed here that perifosine decreased NTAL in lipid raft fractions reducing AKT phosphorylation before apoptosis. We also showed that the NTAL-knockdown by shRNA induced a state of reduced AKT activation. Experimental NTAL-knockdown in NSG mouse MCL xenografts reduced AKT activity, increased the basal apoptotic rate by 3-fold ( n  = 8) and decreased tumor weight by 2.7-fold ( n  = 5), indicating that NTAL participates in tumor growth. NTAL protein was detected by western blotting in circulating cells of 7 of 8 MCL patients in the leukemic phase, suggesting involvement in the progression of the disease.

Objectives: The objective of this study was to evaluate factors related to polypharmacy and the use of potentially inappropriate medications (PIM) in elderly patients with diabetes., Methods: We studied 127 elderly diagnosed with type 2 diabetes, 41 males (age = 69.9 ± 6.9 years) and 86 women (age = 71.1 ± 7.7 years). For evaluation of health conditions, medication use, polypharmacy and associated factors, we used the questionnaire adapted from Morais. The drugs were classified according to the Anatomical Therapeutic-Chemical Classification System, and for identification of MPI, we adopted the criteria of Beers-Fick and PRISCUS. For data analysis, we used descriptive statistics and chi-square and Fisher Exact tests., Results: In this population, 100% of elderly using drugs. The average consumption was 5.8 per individual drug, varying from two to 14, and the prevalence of polypharmacy was 85%. Among the factors studied, only the retirement showed a statistically significant association (p <0.05) with polypharmacy. The most prevalent diseases were hypertension (92.8%), heart problems (70.8%), circulatory (40.8%) and musculoskeletal problems (44.5%). Of drugs used by the elderly, 12 of them were considered potentially inappropriate and 47.2% of the study subjects make use of these medicines regularly., Conclusions: Thus, this study urges new thinking pharmaceutical assistance, as a practical view in full perspective and not meant only as purchasing and dispensing drugs.

The "first hit" to atherogenesis is driven by toll-like receptor 4, endoplasmic reticulum stress and ultimately metabolic dysfunction. In this study, we hypothesized that a flaxseed oil-enriched diet (FS) abolishes these inflammatory signaling pathway and restore metabolic homeostasis by activating the fatty acid receptor GPR120 in aorta of obese mice. Glucose homeostasis was assessed by GTT and ITT; lipidomics was performed using a Hybrid Ion Trap-Orbitrap Mass Spectrometer; serum lipids were measured using colorimetric assays; GPR120 and infiltrating macrophages were analyzed by immunofluorescence; protein immunoprecipitation and gene expression were evaluated by Western blot and RT-PCR, respectively. There were no differences in body weight and food intake between the groups from both strains (Swiss and LDLr-KO mice). GTT and cholesterol levels were improved by FS in both mice models. Lipidomics showed an increase in ω3 (C18:3) content, meanwhile stearic acid (C18:0) was not detected in endothelial tissue in response to FS. Moreover, FS markedly decreased pro-inflammatory (IL-1β, TNF-α, pIκBα, pIKKβ) and unfolded protein response markers (ATF6 and GRP78) in aorta. In Swiss mice, GPR120 was partially involved in the ω3-mediated anti-inflammatory actions, disrupting TLR4 pathway, but not in LDLr-KO mice. Partial replacement of dietary saturated by unsaturated ω3 fatty acids contributes to inhibition of cardiovascular risk markers, pro-inflammatory cytokines and ER stress sensors and effectors in the aorta. However, downregulation of inflammation is not mediated by arterial GPR120 activation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The resilience of ecosystems to negative impacts is generally higher when high gene flow, species diversity and genetic diversity are present. Population genetic studies are suitable to investigate genetic diversity and estimate gene flow between populations. Seaweed beds form a dynamic shallow water ecosystem influenced by climate change and human exploitation, as such, seaweed beds are a particularly powerful model to investigate ecosystem resilience in coastal areas. We studied the population genetic structure of the new nematode species Paracanthonchus gynodiporata associated with seaweeds in northeastern Brazil. Nematodes are generally believed to have a limited dispersal capacity because of the lack of planktonic larvae. Yet, they can drift on seaweeds, and water currents might be a natural barrier for their dispersal. Populations of P. gynodiporata were sampled over more than 1000 km coastline in regions across major oceanic currents with and without historical exploitation of seaweed., Results: P. gynodiporata is described in an integrative way using mitochondrial and nuclear sequences and morphological data. The 3D model of the head region shows for the first time a detailed view of the ventrosublateral teeth, a character often overlooked in older taxonomic studies of the genus. A total of 17 mitochondrial COI haplotypes were found with one haplotype representing 63 to 83% of the frequencies in each population. AMOVA showed overall little population genetic structure (F ST  = 0.05204), and no genetic subdivision between the populations under the influence of the two different water currents were found. Effects of historical seaweed exploitation on population genetic diversity were not detected. In contrast, significant differences between populations were found in morphometric characters. This discrepancy in genetic and morphological differentiation between populations across 1000 km of coastline is surprising in view of the frequently observed presence of several cryptic species at small geographical scale in other macroalgal associated nematodes., Conclusions: Our results show that cryptic species are not omnipresent in marine nematode species, suggesting that nematodes associated with seaweeds have been able to disperse over large distances across well-known biogeographic barriers.

The cardiac chamber's involvement with neoplastic embolism has been rarely reported; it is mostly associated with gastric, breast, lung, liver, and prostate cancers, and usually affects the pulmonary arteries. This paper reports a case of a 31-year-old man with a malignant testicular germ cell tumor who presented with multiple episodes of pulmonary thromboembolism and died of sudden respiratory failure 1 year after the initial diagnosis. Death was attributed to massive pulmonary embolism and pulmonary infarction associated with a neoplastic thrombus that extended from the gonadal veins to pulmonary arteries. A postmortem computerized tomographic angiography and autopsy confirmed this finding., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Postmortem computerized tomographic angiography (PMCTA) has been increasingly used in forensic medicine to detect and locate the source of bleeding in cases of fatal acute hemorrhage. In this paper, we report a case of postoperative complication in a patient with a giant juvenile nasopharyngeal angiofibroma in which the source of bleeding was detected by PMCTA., Methods: A case description and evaluations of the pre- and postoperative exams, postmortem CT angiogram, and conventional autopsy results are provided., Results: The source of bleeding was identified by postmortem CT angiography but not by conventional autopsy. The established protocol, injecting contrast medium into the femoral artery, was effective in identifying the source of bleeding., Conclusions: Postoperative bleeding is a rare and frequently fatal complication of juvenile nasopharyngeal angiofibroma. As a complement to conventional autopsy, postmortem angiography is a valuable tool for the detection of lethal acute hemorrhagic foci, and establishing a routine procedure for PMCTA may improve its efficiency.

In addition to an increase in mean temperature, climate change models predict decreasing amplitudes of daily temperature fluctuations. In temperate regions, where daily and seasonal fluctuations are prominent, such decreases in daily temperature fluctuations can have a pronounced effect on the fitness of species and on the outcome of species interactions. In this study, the effect of a temperature regime with daily fluctuations versus a constant temperature on the fitness and interspecific interactions of three cryptic species of the marine nematode species complex of Litoditis marina (Pm I, Pm III and Pm IV) were investigated. In a lab experiment, different combinations of species (monospecific treatment: Pm I and Pm IV and Pm III alone; two-species treatment: Pm I + Pm IV; three-species treatment: Pm I + Pm IV + Pm III) were subjected to two different temperature regimes: one constant and one fluctuating temperature. Our results showed that fluctuating temperature had minor or no effects on the population fitness of the three species in monocultures. In contrast, interspecific interactions clearly influenced the fitness of all three species, both positively and negatively. Temperature regime did have a substantial effect on the interactions between the species. In the two-species treatment, temperature regime altered the interaction from a sort of mutualism to commensalism. In addition, the strength of the interspecific interactions changed depending on the temperature regime in the three-species treatment. This experiment confirms that interactions between the species can change depending on the abiotic environment; these results show that it is important to incorporate the effect of fluctuations on interspecific interactions to predict the effect of climate change on biodiversity.

Background: The social reality of the albino needs to be more studied in Brazil, as myths and social segregation regarding this illness are likely to be found in the country, with psychosocial and medical implications., Objective: As this subject has not been referenced in previous scientific articles in Brazil, this research intends to evaluate the quality of life of the albinos that treated at our medical institution., Methods: The quality of life was evaluated through the WHOQOL-BREF. Furthermore, two aspects of main relevance in the lives of the albinos were also objects of research, low vision and skin cancer. The sample consisted of forty oculocutaneous albinos and a control group of forty healthy individuals, matched by sex and age., Results: Among the participants, 57.7% were between 18 and 40 years old, 28.2% were between 41 and 60, and 14.1% were over 60. 42.1% had skin cancer before the study, 18.4% had skin cancer during the study and 89.5% stated visual deficit. The results obtained in the questionnaires showed a statistically significant difference in the physical domain, with P < 0.001., Conclusion: Low vision combined with skin lesions and social stigma may contribute to disturbances in the quality of life of oculocutaneous albinos. The results presented in this study demonstrated the vulnerability of the affected individuals and the special care required by those patients, at the same time that the need for further research is highlighted in order to better elucidate the aspects related to albinism.

Nonalcoholic steatohepatitis (NASH) is a fatty liver disorder that could be improved with extra virgin olive oil (EVOO) supplementation in diet. We propose the monitoring, in whole mouse liver extracts and in isolated mitochondria, of the absorption of compounds from three different diets: standard (CT), high-fat (HFD) and high-fat supplemented with EVOO (HFSO). Male mice were submitted to one of the following three diets: CT or HFD for 16 weeks or HFD for 8 weeks followed by additional 8 weeks with HFSO. Following this period, liver was extracted for histological evaluation, mitochondria isolation and mass spectrometry analyses. Diets, liver extracts and Percoll-purified mitochondria were analyzed using ESI-MS and the lipidomics approach. Morphological, histological and spectrometric results indicated a decrease in NASH severity with EVOO supplementation in comparison with animals maintained with HFD. Spectrometric data also demonstrated that some compounds presented on the diets are absorbed by the mitochondria. EVOO was shown to be a potential therapeutic alternative in food for NASH. Our results are in accordance with the proposition that the major factor that influences different responses to diets is their composition - and not only calories - especially when it comes to studies on obesity., (Copyright © 2015 John Wiley & Sons, Ltd.)