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1.
Andes Pediatr ; 95(1): 34-40, 2024 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-38587342

RESUMO

Clinical control and monitoring of bilirubin in the neonatal stage are essential to avoid toxicity in the central nervous system. OBJECTIVE: to determine the correlation between transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) levels in newborns ≥ 35 weeks. PATIENTS AND METHOD: observational, cross-sectional, analytical, retrospective study that included 90 neonates of gestational age ≥ 35 weeks with mucocutaneous jaundice who underwent TcB and TSB measurement simultaneously between June 1, 2022, and January 31, 2023. Both variables were compared, determining their correlation. RESULTS: the validity indicators were analyzed, obtaining 100% sensitivity and negative predictive value. The mean of TcB determinations was 14.84 mg/dl ± 2.27 and that of TSB was 13.1 mg/dl ± 2.39. The correlation obtained indicates that both variables are related, which is a direct correlation and, according to the prediction equation, there is an appropriate correlation between them. It was determined that TcB overestimated TSB in 95.56% of the determinations, and underestimated TSB in the rest (4.44%). Simultaneous measurements of TcB and TSB were different in all determinations with a mean difference of 1.72 ± 1.48. CONCLUSIONS: the non-invasive TcB method can be used as an initial screening tool for the neonatal population ≥ 35 weeks, given its adequate sensitivity and negative predictive value.


Assuntos
Bilirrubina , Triagem Neonatal , Humanos , Recém-Nascido , Estudos Transversais , Idade Gestacional , Triagem Neonatal/métodos , Estudos Retrospectivos
2.
Eur J Med Chem ; 264: 116021, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38086194

RESUMO

Different studies using Aprepitant, a NK1R antagonist currently used as a clinical drug for treating chemotherapy-related nausea and vomiting, have demonstrated that pharmacological inhibition of NK1R effectively reduces the growth of several tumor types such as neuroblastoma (NB). In a previous work, we demonstrated that a series of carbohydrate-based Aprepitant analogs, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity. In this new study, we explore the selective cytotoxic effects of these derivatives for the treatment of NB. Furthermore, we describe the design and stereoselective synthesis of a new generation of d-glucose derivatives as Aprepitant analogs, supported by docking studies. This approach showed that most of our carbohydrate-based analogs are significantly more selective than Aprepitant. The galactosyl derivative 2α, has demonstrated a marked in vitro selective cytotoxic activity against NB, with IC50 values in the same range as those of Aprepitant and its prodrug Fosaprepitant. Interestingly, the derivative 2α has shown similar apoptotic effect to that of Aprepitant. Moreover, we can select the glucosyl amino derivative 10α as an interesting hit exhibiting higher in vitro cytotoxic activity against NB than Aprepitant, being 1.2 times more selective.


Assuntos
Antieméticos , Antineoplásicos , Neuroblastoma , Humanos , Aprepitanto/farmacologia , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Vômito/tratamento farmacológico , Antineoplásicos/farmacologia , Neuroblastoma/tratamento farmacológico , Carboidratos , Antieméticos/uso terapêutico
3.
Rev. esp. patol ; 56(4): 233-242, Oct-Dic, 2023. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-226956

RESUMO

Introducción: El cáncer de pulmón es la principal causa de muerte por cáncer en nuestro país. El cáncer de pulmón de células no pequeñas (CPCNP) representa el paradigma de la medicina personalizada. El objetivo principal de este trabajo es estudiar la frecuencia en nuestro medio de las variantes clínicamente significativas más frecuentemente descritas en CPCNP. Material y métodos: Se estudia la expresión inmunohistoquímica de TTF1, p40 y PD-L1 y la frecuencia de variantes genéticas mediante secuenciación masiva (NGS) con un panel de 52 genes, en 174 muestras incluidas en parafina de CPNCP en 169 pacientes (111 hombres y 52 mujeres) de la provincia de Cádiz. Resultados: La expresión inmunohistoquímica de TTF1, p40 y PD-L1 fue positiva en el 87%, el 0% y el 46% de los adenocarcinomas y en el 0%, el 100% y el 41% de los carcinomas escamosos. En NGS, las variantes de un solo nucleótido (SNV) más frecuentes fueron KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%) y MET (3%). Las variantes en el número de copias (CNV) más frecuentes fueron las amplificaciones en NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) y KRAS (7%). En mujeres, las SNV en EGFR fueron más frecuentes que en hombres (p<0,0001). El adenocarcinoma es el tipo histológico más frecuente con SNV en KRAS (p=0,007361) o en EGFR (p<0,0001). En 16 pacientes (9,47%) se detectaron fusiones génicas, 9 casos en el gen MET. Conclusiones: Detectamos nuevas asociaciones entre expresión inmunohistoquímica y algunas variantes génicas, que podrían tener impacto en el tratamiento de pacientes de CPNCP.(AU)


Introduction: Lung cancer is the leading cause of cancer death in our country. Non-small cell lung cancer (NSCLC) represents the paradigm of personalized medicine. The main objective of this study is analysing the distribution of the most frequently described clinically significant variants in NSCLC, in our environment. Material and methods: We studied the immunohistochemical expression of TTF1, p40 and PD-L1 and the genetic variants frequency using Next-Generation Sequencing (NGS) with a panel of 52 genes, in 174 NSCLC paraffin-embedded samples in 169 patients (111 men and 52 women) from the province of Cádiz. Results: The immunohistochemical expression of TTF1, p40 and PD-L1 was positive in 87%, 0% and 46% in adenocarcinoma, and 0%, 100% and 41% in squamous cell carcinoma. In NGS, the most common single nucleotide variants (SNVs) were KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%), and MET (3%). The most frequent copy number variants (CNVs) were amplifications in NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) and KRAS (7%). In women, SNV in EGFR are more frequent than in men (P<.0001). Adenocarcinoma is the most frequent histological type with SNV in KRAS (P=.007361) or in EGFR (P<.0001). Gene fusions were detected in 16 patients (9.47%), in 9 cases in the MET gene. Conclusions: We detected associations, not described so far, between immunohistochemical expression and specific gene variants, which could have an impact on the treatment of NSCLC patients.(AU)


Assuntos
Humanos , Masculino , Feminino , Imuno-Histoquímica , Carcinoma Pulmonar de Células não Pequenas/genética , Genes erbB-1 , Sequenciamento de Nucleotídeos em Larga Escala , Espanha , Neoplasias Pulmonares/genética , Biologia Celular
4.
Rev Esp Patol ; 56(4): 233-242, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-37879820

RESUMO

INTRODUCTION: Lung cancer is the leading cause of cancer death in our country. Non-small cell lung cancer (NSCLC) represents the paradigm of personalized medicine. The main objective of this study is analysing the distribution of the most frequently described clinically significant variants in NSCLC, in our environment. MATERIAL AND METHODS: We studied the immunohistochemical expression of TTF1, p40 and PD-L1 and the genetic variants frequency using Next-Generation Sequencing (NGS) with a panel of 52 genes, in 174 NSCLC paraffin-embedded samples in 169 patients (111 men and 52 women) from the province of Cádiz. RESULTS: The immunohistochemical expression of TTF1, p40 and PD-L1 was positive in 87%, 0% and 46% in adenocarcinoma, and 0%, 100% and 41% in squamous cell carcinoma. In NGS, the most common single nucleotide variants (SNVs) were KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%), and MET (3%). The most frequent copy number variants (CNVs) were amplifications in NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) and KRAS (7%). In women, SNV in EGFR are more frequent than in men (P<.0001). Adenocarcinoma is the most frequent histological type with SNV in KRAS (P=.007361) or in EGFR (P<.0001). Gene fusions were detected in 16 patients (9.47%), in 9 cases in the MET gene. CONCLUSIONS: We detected associations, not described so far, between immunohistochemical expression and specific gene variants, which could have an impact on the treatment of NSCLC patients.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Proteínas Proto-Oncogênicas p21(ras) , Adenocarcinoma/genética , Receptores ErbB/genética
5.
Diagnostics (Basel) ; 13(13)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37443647

RESUMO

Peritoneal carcinomatosis (PC) refers to malignant epithelial cells that spread to the peritoneum, principally from abdominal malignancies. Until recently, PC prognosis has been considered ill-fated, with palliative therapies serving as the only treatment option. New locoregional treatments are changing the outcome of PC, and imaging modalities have a critical role in early diagnosis and disease staging, determining treatment decision making strategies. The aim of this review is to provide a practical approach for detecting and characterizing peritoneal deposits in cross-sectional imaging modalities, taking into account their appearances, including the secondary complications, the anatomical characteristics of the peritoneal cavity, together with the differential diagnosis with other benign and malignant peritoneal conditions. Among the cross-sectional imaging modalities, computed tomography (CT) is widely available and fast; however, magnetic resonance (MR) performs better in terms of sensitivity (92% vs. 68%), due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR mainly depends on the primary tumour histology; in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights into the tumour origin. The timepoint of tumour evolution, previous or ongoing treatments, and the peritoneal spaces in which they occur also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is essential in the detection and characterisation of peritoneal deposits. Several benign and malignant conditions show similar imaging features that overlap those of PC, making differential diagnosis challenging. Knowledge of peritoneal anatomy and primary tumour histology is crucial, but one must also consider clinical history, laboratory findings, and previous imaging examinations to achieve a correct diagnosis. In conclusion, to correctly diagnose PC in cross-sectional imaging modalities, knowledge of peritoneal anatomy and peritoneal fluid flow characteristics are mandatory. Peritoneal deposit features reflect the primary tumour characteristics, and this specificity may be helpful in its identification when it is unknown. Moreover, several benign and malignant peritoneal conditions may mimic PC, which need to be considered even in oncologic patients.

6.
Org Biomol Chem ; 21(28): 5827-5839, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37401653

RESUMO

A series of enantiopure chiral NH2/SO palladium complexes have been synthesised with high yields by treating the corresponding tert-butylsulfinamide/sulfoxide derivatives with Pd(CH3CN)2Cl2. The enantiopure chiral ligands were prepared by stereoselective addition of tert-butyl or phenyl methylsulfinyl carbanions to different tert-butylsulfinylimines. In all cases, coordination occurs with concomitant desulfinylation. X-ray studies of the Pd complexes showed a higher trans influence of the phenylsulfinyl group in comparison to that of the tert-butylsulfinyl group. Furthermore, we have obtained and characterised two possible palladium amine/sulfonyl complexes, epimers at sulfur, resulting from N-desulfinylation and coordination of palladium with both oxygens of the prochiral sulfonyl group. The catalytic activity and enantioselectivity of the new Pd(II) complexes of acetylated amine/tert-butyl- and phenylsulfoxides in the carboxylated cyclopropanes arylation reaction has been studied, obtaining the best results with the phenylsulfoxide ligand 25(SC,SS) that produced the final arylated product in a 93 :7 enantiomeric ratio.

7.
Food Funct ; 14(15): 7270-7283, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37469300

RESUMO

The aim of this study was to develop an optimal synthetic route to obtain natural (R)-8-methylsulfinyloctyl isothiocyanate ((R)-8-OITC), present in watercress, based on the "DAG methodology" as well as to evaluate its potential antioxidant and immunomodulatory effects, exploring possible signaling pathways that could be involved in an ex vivo model of murine peritoneal macrophages stimulated with LPS. Treatment with (R)-8-OITC inhibited the levels of pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-17 and IL-18), intracellular ROS production and expression of pro-inflammatory enzymes (COX-2, iNOS and mPGES-1) through modulation of the expression of Nrf2, MAPKs (p38, JNK and ERK) and JAK/STAT, and the canonical and non-canonical pathways of the inflammasome. Taking all these together, our results provide a rapid and cost-effective synthetic route to obtain natural (R)-8-OITC and demonstrate that it could be a potential nutraceutical candidate for managing immuno-inflammatory pathologies. Therefore, further in vivo trials are warranted.

8.
Health Promot Int ; 38(1)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36738452

RESUMO

The current state of knowledge indicates that regular sports practice helps prevent and treat non-communicable diseases. The promotion of sport is, therefore, an important community health intervention for maintaining and improving the health of individuals and populations. Culture is identified as being associated with sports practice and sedentary behaviour of ethnic and national minorities. This study aims qualitatively to analyse the potential for culture as a basis for the promotion of sport among immigrants in four regions of Mediterranean Europe. Ten focus groups (n = 62) were conducted with immigrants-adults and young people over the age of 11-and people involved in promoting sport. Thematic content analysis was conducted. The results enabled identifying two major issues: sport as a vehicle for cultural expression and synergies between sport and culture. Accordingly, sport serves to express global, local and non-ethno-national cultural belonging. Regarding synergies, culture and sport feed each other positively and contribute to immigrants' health and cultural well-being. Culture as a strategy for promoting sports practice requires an interdisciplinary approach that involves collaboration between healthcare practitioners and social sciences professionals. There is also a need to use the various axes of cultural definition-global, local and non-ethno-national-of those involved, and for them to take part themselves in designing sports activities. Moreover, promoting sport through non-ethno-national axes of cultural definition may help with immigrants' social inclusion, as intercultural relations between migrants and newcomers are promoted.


Assuntos
Dança , Emigrantes e Imigrantes , Futebol Americano , Futebol , Adulto , Humanos , Adolescente , Europa (Continente)
9.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674634

RESUMO

Rhabdoid meningiomas (RM) shows heterogeneous histological findings, and a wide variety of chromosomal copy number alterations (CNA) are associated with an unpredictable course of the disease. In this study, we analyzed a series of 305 RM samples from patients previously reported in the literature and 33 samples from 23 patients studied in our laboratory. Monosomy 22-involving the minimal but most common recurrent region loss of the 22q11.23 chromosomal region was the most observed chromosomal alteration, followed by losses of chromosomes 14, 1, 6, and 19, polysomies of chromosomes 17, 1q, and 20, and gains of 13q14.2, 10p13, and 21q21.2 chromosomal regions. Based on their CNA profile, RM could be classified into two genetic subgroups with distinct clinicopathologic features characterized by the presence of (1) chromosomal losses only and (2) combined losses and gains of several chromosomes. The latter displays a higher frequency of WHO grade 3 tumors and poorer clinical outcomes.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/patologia , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Aberrações Cromossômicas , Monossomia
11.
Mol Omics ; 18(10): 1015-1028, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36382626

RESUMO

Digital pathology and genomics are increasingly used to improve our understanding of lymphoid neoplasms. Algorithms for quantifying cell populations in the lymph node and genetics can be integrated to identify new biomarkers with prognostic impact in classic Hodgkin lymphoma (cHL). In 16 cHL patients, we have performed whole slide imaging (WSI) analysis and quantification of CD30+, CD20+, CD3+ and MUM1+ cells in whole tissue slides, and Next Generation Sequencing (NGS) in formalin fixed paraffin-embedded (FFPE) tissue, using a widely used NSG panel (Oncomine® Focus Assay) to define genetic variants underlying tumor development. The different cell populations could be successfully identified in scanned slides of cHL, supporting the inclusion of WSI in the histopathological evaluation of cHL as an adequate method for the quantification of different cell populations. We also performed genetic profiling in FFPE samples of cHL leading to the identification of copy number variations in the Neurofibromin 1 gene (17q11.2) and the Androgen Receptor gene (Xq12) accompanied by chromosomal gains and losses in CDK4, KRAS and FGFR2 genes. Progression-free survival (PFS) was statistically significantly higher in cHL patients with amplification in the NF1 gene combined with CD3+ cells above 28.6% (p = 0.006) and MUM1+ cells above 21.8% (p < 0.001). Moreover, patients with MUM1+ cells above 21.8% showed a statistically significantly higher PFS when combined with amplification of the AR gene (p < 0.001) and wild-type KRAS (p < 0.001). The integration of WSI analysis and DNA sequencing could be useful to improve our understanding of the biology of cHL and define risk subgroups.


Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/genética , Doença de Hodgkin/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Variações do Número de Cópias de DNA , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
12.
Eur J Med Chem ; 243: 114730, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36088758

RESUMO

The stereoselective addition of ethyl acetate enolate to the C═N bond of N-tert-butylsulfinylimines has been investigated in depth. A significant effect of the LHMDS amount and the N-sulfinylimine nature on the stereoselectivity of the process was observed. Conditions were found where sulfinylimines of differently substituted salicylaldehydes derivatives, ethyl acetate, and LHMDS afforded the corresponding addition products as a single diastereomer in good yields. The developed protocol was successfully applied to the first stereoselective synthesis of differently substituted 4-amino-3,4-dihydrocoumarin derivatives. Computational models confirmed the prominent role of the ortho aryl substituent in the stereoselectivity of the process. A significant and selective cytotoxic activity against Glioblastoma Multiforme (GBM) cancer line has been determined for the noncyclic hydroxy ester derivative.


Assuntos
Antineoplásicos , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Estereoisomerismo , Ésteres/farmacologia , Ésteres/química , Antineoplásicos/farmacologia
13.
Pharmaceuticals (Basel) ; 15(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36015085

RESUMO

The antiproliferative effects played by benzothiazoles in different cancers have aroused the interest for these molecules as promising antitumor agents. In this work, a library of phenylacetamide derivatives containing the benzothiazole nucleus was synthesized and compounds were tested for their antiproliferative activity in paraganglioma and pancreatic cancer cell lines. The novel synthesized compounds induced a marked viability reduction at low micromolar concentrations both in paraganglioma and pancreatic cancer cells. Derivative 4l showed a greater antiproliferative effect and higher selectivity index against cancer cells, as compared to other compounds. Notably, combinations of derivative 4l with gemcitabine at low concentrations induced enhanced and synergistic effects on pancreatic cancer cell viability, thus supporting the relevance of compound 4l in the perspective of clinical translation. A target prediction analysis was also carried out on 4l by using multiple computational tools, identifying cannabinoid receptors and sentrin-specific proteases as putative targets contributing to the observed antiproliferative activity.

14.
Pharmaceuticals (Basel) ; 15(8)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-36015113

RESUMO

The aim of this study was to explore the immunomodulatory effects of the natural enantiomer (R)-Sulforaphane (SFN) and the possible signaling pathways involved in an ex vivo model of LPS-stimulated murine peritoneal macrophages. Furthermore, we studied the epigenetic changes induced by (R)-SFN as well as the post-translational modifications of histone H3 (H3K9me3 and H3K18ac) in relation to the production of cytokines in murine splenocytes after LPS stimulation. (R)-SFN was able to modulate the inflammatory response and oxidative stress induced by LPS stimulation in murine peritoneal macrophages through the inhibition of reactive oxygen species (ROS), nitric oxide (NO) and cytokine (IL-1ß, IL-6, IL-17, IL-18 and TNF-α) production by down-regulating the expression of pro-inflammatory enzymes (iNOS, COX-2 and mPGES-1). We also found that activation of the Nrf-2/HO-1 axis and inhibition of the JAK2/STAT-3, MAPK, canonical and non-canonical inflammasome signaling pathways could have been responsible for the immunomodulatory effects of (R)-SFN. Furthermore, (R)-SFN modulated epigenetic modifications through histone methylation (H3K9me3) and deacetylation (H3K18ac) in LPS-activated spleen cells. Collectively, our results suggest that (R)-SFN could be a promising epinutraceutical compound for the management of immunoinflammatory diseases.

15.
Nanomaterials (Basel) ; 12(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35630975

RESUMO

The preparation of new and functional nanostructures has received more attention in the scientific community in the past decade due to their wide application versatility. Among these nanostructures, micelles appear to be one of the most interesting supramolecular organizations for biomedical applications because of their ease of synthesis and reproducibility and their biocompatibility since they present an organization similar to the cell membrane. In this work, we developed micellar nanocarrier systems from surfactant molecules derived from oleic acid and tetraethylene glycol that were able to encapsulate and in vitro release the drug dexamethasone. In addition, the designed micelle precursors were able to functionalize metallic NPs, such as gold NPs and iron oxide NPs, resulting in monodispersed hybrid nanomaterials with high stability in aqueous media. Therefore, a new triazole-derived micelle precursor was developed as a versatile encapsulation system, opening the way for the preparation of new micellar nanocarrier platforms for drug delivery, magnetic resonance imaging, or computed tomography contrast agents for therapeutic and diagnostic applications.

16.
Cancers (Basel) ; 14(10)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35625981

RESUMO

In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones. We also investigated the correlation of the most interesting SNPs with cytokine levels after in vitro stimulation of whole blood, peripheral mononuclear cells (PBMCs), and monocyte-derived macrophages with LPS, PHA, Pam3Cys, and Staphylococcus Aureus. The meta-analysis of our data with those from six large cohorts confirmed that each copy of the FTOrs9939609A, HNF1Brs7501939T, HNF1Brs757210T, HNF1Brs4430796G, and JAZF1rs10486567A alleles significantly decreased risk of developing PCa (p = 3.70 × 10-5, p = 9.39 × 10-54, p = 5.04 × 10-54, p = 1.19 × 10-71, and p = 1.66 × 10-18, respectively). Although it was not statistically significant after correction for multiple testing, we also found that the NOTCH2rs10923931T and RBMS1rs7593730 SNPs associated with the risk of developing PCa (p = 8.49 × 10-4 and 0.004). Interestingly, we found that the protective effect attributed to the HFN1B locus could be mediated by the SULT1A1 protein (p = 0.00030), an arylsulfotransferase that catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. In addition to these results, eQTL analysis revealed that the HNF1Brs7501939, HNF1Brs757210, HNF1Brs4430796, NOTCH2rs10923931, and RBMS1rs7593730 SNPs influence the risk of PCa through the modulation of mRNA levels of their respective genes in whole blood and/or liver. These results confirm that functional TD2-related variants influence the risk of developing PCa, but also highlight the need of additional experiments to validate our functional results in a tumoral tissue context.

17.
Commun Med (Lond) ; 2: 20, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603271

RESUMO

Background: Direct-acting antivirals can cure ≥95% of hepatitis C virus (HCV) cases, but do not reach everyone in need. This cross-sectional study analyses the HCV cascade of care (CoC) in Madrid, Spain, in high-risk patients, to inform micro-elimination measures. Methods: From September 2019 to May 2021, data from medical records were collected and analysed from six public hospitals in Madrid, including seven adult, high-risk patient groups: patients in haemodialysis or pre-dialysis programmes, co-infected with HIV, with advanced liver disease (ALD), with hereditary haematological diseases, with transplants and people who inject drugs (PWID). Results: Here we present an analysis of 3994 patients (68.8% male), 91.2% were tested for anti-HCV and 28.9% were positive. Of the total, 34.5% were tested for HCV-RNA and 62.4% of these were positive. Of those HCV-RNA positive, 98.0% were treatment-eligible: in 7.4%, treatment is ongoing and in 89.3% completed. Of the latter, 92.2% obtained a sustained virological response 12 weeks post treatment (SVR12). Of those with ongoing or completed treatment, 9.8% experienced loss to follow-up (LTFU) or had unknown SVR12, 50.3% developed hepatic and 20.3% extrahepatic complications. ALD patients had the highest proportion of HCV-RNA positives (32.5%). The lowest proportion of patients treated were PWID (85.2%). Conclusions: Almost one in ten high-risk patients in six of Madrid's public hospitals remains untested for HCV antibodies. An almost equal percentage of those untested have experienced LTFU, with the highest proportion in PWID. This approach to monitoring the HCV CoC is vital to inform measures to eliminate HCV in hospitals.

18.
J Agric Food Chem ; 70(12): 3644-3653, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35289164

RESUMO

The encapsulation of bioactive natural products has emerged as a relevant tool for modifying the poor physicochemical properties often exhibited by agrochemicals. In this regard, natural guaiane-type sesquiterpene lactones isolated from Cynara cardunculus L. have been encapsulated in a core/shell nanotube@agrochemical system. Monitoring of the F and O signals in marked sesquiterpenes confirmed that the compound is present in the nanotube cavity. These structures were characterized using scanning transmission electron microscopy-X-ray energy-dispersive spectrometry techniques, which revealed the spatial layout relationship and confirmed encapsulation of the sesquiterpene lactone derivative. In addition, biological studies were performed with aguerin B (1), cynaropicrin (2), and grosheimin (3) on the inhibition of germination, roots, and shoots in weeds (Phalaris arundinacea L., Lolium perenne L., and Portulaca oleracea L.). Encapsulation of lactones in nanotubes gives better results than those for the nonencapsulated compounds, thereby reinforcing the application of fully organic nanotubes for the sustainable use of agrochemicals in the future.


Assuntos
Cynara , Nanotubos , Cynara/química , Lactonas/química , Lactonas/toxicidade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sesquiterpenos de Guaiano
19.
World J Gastroenterol ; 27(41): 7113-7124, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34887631

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common cause of liver disease. Its prevalence is increasing in parallel with the obesity and type 2 diabetes mellitus (DM2) epidemics in developed countries. Several recent studies have suggested that NAFLD may be the hepatic manifestation of a systemic inflammatory metabolic disease that also affects other organs, such as intestine, lungs, skin and vascular endothelium. It appears that local and systemic proinflammatory/anti-inflammatory cytokine imbalance, together with insulin resistance and changes in the intestinal microbiota, are pathogenic mechanisms shared by NAFLD and other comorbidities. NAFLD is more common in patients with extrahepatic diseases such as inflammatory bowel disease (IBD), obstructive syndrome apnea (OSA) and psoriasis than in the general population. Furthermore, there is evidence that this association has a negative impact on the severity of liver lesions. Specific risk characteristics for NAFLD have been identified in populations with IBD (i.e. age, obesity, DM2, previous bowel surgery, IBD evolution time, methotrexate treatment), OSA (i.e. obesity, DM2, OSA severity, increased transaminases) and psoriasis (i.e. age, metabolic factors, severe psoriasis, arthropathy, elevated transaminases, methotrexate treatment). These specific phenotypes might be used by gastroenterologists, pneumologists and dermatologists to create screening algorithms for NAFLD. Such algorithms should include non-invasive markers of fibrosis used in NAFLD to select subjects for referral to the hepatologist. Prospective, controlled studies in NAFLD patients with extrahepatic comorbidities are required to demonstrate a causal relationship and also that appropriate multidisciplinary management improves these patients' prognosis and survival.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Psoríase , Humanos , Intestinos , Pulmão , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Estudos Prospectivos , Fatores de Risco
20.
Polymers (Basel) ; 13(23)2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34883653

RESUMO

In oil-immersed power transformers, the insulation system is constituted of a dielectric oil-solid combination. The insulation oil generally used is mineral oil; however, this fluid has started to be substituted by natural and synthetic esters due to their higher biodegradability and flash point. The introduction of a new fluid in the insulation system of power transformers requires kinetic models that can estimate the degradation rate of insulation solids. The aim of this work was to go further in quantifying through different kinetic models the deterioration suffered by a commercial cellulose board (PSP 3055), which is one of the solid materials used in the insulation system of oil-filled transformers. The aging study was extended to cellulose board specimens immersed in two different oils (mineral and synthetic ester). It was obtained that there is a lower degradation when synthetic ester is used in the insulation system. Additionally, it can be concluded that the use of mechanical properties to quantify the degradation of the cellulose board through kinetic models provides information about the different behavior shown by PSP 3055 when different fiber direction angles are considered.

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