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2.
Int J Cardiol ; 409: 132177, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38761976

RESUMEN

BACKGROUND: The prognostic significance of inflammatory markers on the long-term risk of major adverse cardiovascular and cerebrovascular events (MACCE) in older NSTEACS patients remains unclear. METHODS: NSTEACS patients aged 75 and older were recruited to the multicentre cohort study Improve Cardiovascular Outcomes in High-Risk PatieNts with Acute Coronary Syndrome (ICON1). Inflammatory markers including interleukin-6 (IL-6), myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), fibrinogen and tumor necrosis factor-alpha (TNF-α) were collected at baseline. Primary outcome was MACCE consisting of all-cause mortality, reinfarction, stroke/transient ischaemic attack, urgent revascularization, and significant bleeding at 5-year follow-up. RESULTS: There were 230 patients with baseline IL-6 (median age 80.9 [interquartile range (IQR):78.2-83.9] years). High IL-6 was not associated with MACCE, but it was independently associated with all-cause mortality (adjusted hazard ratio [aHR]: 2.26 [95% Confidence Interval (CI):1.34-3.82]; P = 0.002). For patients with hsCRP (n = 260, median age 80.9 [IQR:77.9-84.1] years), higher levels were significantly associated with increased risk of MACCE (aHR:1.77 [95% CI:1.26-2.49], P = 0.001). In the cohort with MPO (230 patients, median age 80.9 [IQR:78.2-83.9] years), lower MPO was independently associated with the risk of MACCE (aHR: 0.67 [95%CI:0.46-0.96]; P = 0.029). There was no prognostic significance with fibrinogen and TNF-α. CONCLUSION: Among older NSTEACS patients, elevated IL-6 and hsCRP were associated with increased risk of all-cause mortality and MACCE, respectively. Low MPO levels were associated with higher MACCE. Further studies are required to determine how these biomarkers should influence treatment strategy in this understudied subset. CLINICAL TRIAL REGISTRATION: NCT01933581.


Asunto(s)
Síndrome Coronario Agudo , Biomarcadores , Humanos , Masculino , Femenino , Anciano , Biomarcadores/sangre , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/diagnóstico , Anciano de 80 o más Años , Estudios de Seguimiento , Estudios de Cohortes , Inflamación/sangre , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Factores de Tiempo , Interleucina-6/sangre , Resultado del Tratamiento , Pronóstico , Peroxidasa/sangre
3.
J Clin Med ; 13(8)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38673452

RESUMEN

Background: Metatarsalgia is a common pathology that is initially treated conservatively, but failure to do so requires surgery, such as the minimally invasive distal metatarsal osteotomy (DICMO). Methods: In this prospective study of 65 patients with primary metatarsalgia who underwent DICMO, plantar pressures, American Orthopaedic Foot and Ankle Society MetaTarsoPhalangeal-InterPhalangeal scale (AOFAS-MTP-IP) and Visual Analog Scale (VAS) were evaluated pre-operatively and post-operatively and there was a subgroup in which an inclinometer was used to observe the importance of the inclination of the osteotomy. Results: The results show a significant reduction in plantar pressures after DICMO surgery without overloading the adjacent radii, especially in the subgroup with an inclinometer to guide the osteotomy. The AOFAS-MTP-IP scale evidenced a marked improvement in metatarsal function and alignment with scores close to normal. The VAS scale showed a substantial decrease in pain after DICMO osteotomy. Conclusions: DICMO, with an inclinometer for a 45° osteotomy, proved to be a safe and effective procedure for primary metatarsalgia, although further comparative studies are needed to confirm its superiority.

4.
Redox Biol ; 72: 103150, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38599016

RESUMEN

Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by impaired motor coordination due to neurological defects and cerebellar dysfunction caused by the accumulation of cholesterol in endolysosomes. Besides the increase in lysosomal cholesterol, mitochondria are also enriched in cholesterol, which leads to decreased membrane fluidity, impaired mitochondrial function and loss of GSH, and has been shown to contribute to the progression of NPC disease. S-Adenosyl-l-methionine (SAM) regulates membrane physical properties through the generation of phosphatidylcholine (PC) from phosphatidylethanolamine (PE) methylation and functions as a GSH precursor by providing cysteine in the transsulfuration pathway. However, the role of SAM in NPC disease has not been investigated. Here we report that Npc1-/- mice exhibit decreased brain SAM levels but unchanged S-adenosyl-l-homocysteine content and lower expression of Mat2a. Brain mitochondria from Npc1-/- mice display decreased mitochondrial GSH levels and liquid chromatography-high resolution mass spectrometry analysis reveal a lower PC/PE ratio in mitochondria, contributing to increased mitochondrial membrane order. In vivo treatment of Npc1-/- mice with SAM restores SAM levels in mitochondria, resulting in increased PC/PE ratio, mitochondrial membrane fluidity and subsequent replenishment of mitochondrial GSH levels. In vivo SAM treatment improves the decline of locomotor activity, increases Purkinje cell survival in the cerebellum and extends the average and maximal life spam of Npc1-/- mice. These findings identify SAM as a potential therapeutic approach for the treatment of NPC disease.


Asunto(s)
Encéfalo , Glutatión , Fluidez de la Membrana , Membranas Mitocondriales , Enfermedad de Niemann-Pick Tipo C , S-Adenosilmetionina , Animales , Ratones , S-Adenosilmetionina/metabolismo , Membranas Mitocondriales/metabolismo , Enfermedad de Niemann-Pick Tipo C/metabolismo , Enfermedad de Niemann-Pick Tipo C/tratamiento farmacológico , Enfermedad de Niemann-Pick Tipo C/genética , Glutatión/metabolismo , Encéfalo/metabolismo , Mitocondrias/metabolismo , Proteína Niemann-Pick C1 , Modelos Animales de Enfermedad , Ratones Noqueados , Fosfatidilcolinas/metabolismo
5.
J Pediatr Nurs ; 77: 63-73, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38479064

RESUMEN

BACKGROUND: Music therapy is an emerging and useful methodology for improving patient environments within healthcare fields. However, although it has been shown that music therapy interventions with hospitalised children and adolescents have been used for decades with positive effects, there are currently very few studies that specifically describe the perspectives of healthcare professionals regarding the value of music therapy when applied in these patients. OBJECTIVES: To describe the insights of healthcare professionals regarding music therapy, both on a personal level and in terms of its usefulness in the care of hospitalised children and adolescents. DESIGN: This was a qualitative descriptive-exploratory study with focus groups. PARTICIPANTS: Eighteen healthcare professionals. METHODS: In January 2023, two focus groups, containing nine healthcare professionals each, were created to collect data regarding their experiences concerning the effect of music therapy on hospitalised children and adolescents. Before recording their opinions, all these professionals participated in an interactive music therapy session. The thematic analysis in this work was performed using MAXQDA® software. RESULTS: Two main categories emerged: (a) the effects of music therapy on healthcare professionals, and (b) the benefits of music therapy to patients (children and adolescents). CONCLUSIONS: Music therapy was valued positively by healthcare professionals who described the benefits its use has for hospitalised children and adolescents. They also expressed positive viewpoints regarding the use of music therapy to improve their own self-knowledge and self-care. IMPLICATIONS TO PRACTICE: Healthcare professionals may utilise music therapists to improve patient outcomes and reduce the negative effects of hospitalisation.

6.
Sci Rep ; 14(1): 5462, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443503

RESUMEN

Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008-2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2-2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1-8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7-13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population.


Asunto(s)
Leucemia Felina , Lynx , Animales , Gatos , Humanos , Virus de la Leucemia Felina/genética , España/epidemiología , ADN
7.
Brain ; 147(5): 1899-1913, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38242545

RESUMEN

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, and the effects on cell membranes and the wider cell were also unknown. Using patient-derived cells, we show that cholesterol perturbation is a conserved feature of pathological ATAD3 variants that is accompanied by an expanded lysosome population containing membrane whorls characteristic of lysosomal storage diseases. Lysosomes are also more numerous in Drosophila neural progenitor cells expressing mutant Atad3, which exhibit abundant membrane-bound cholesterol aggregates, many of which co-localize with lysosomes. By subjecting the Drosophila Atad3 mutant to nutrient restriction and cholesterol supplementation, we show that the mutant displays heightened cholesterol dependence. Collectively, these findings suggest that elevated cholesterol enhances tolerance to pathological ATAD3 variants; however, this comes at the cost of inducing cholesterol aggregation in membranes, which lysosomal clearance only partly mitigates.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas , Colesterol , Lisosomas , Proteínas de la Membrana , Mutación , Animales , Colesterol/metabolismo , Humanos , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Lisosomas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Drosophila , Membrana Celular/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo
8.
J Midwifery Womens Health ; 69(1): 71-90, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37531180

RESUMEN

INTRODUCTION: Dealing with intercultural communicative barriers in European countries' national health services is an increasing and necessary challenge to guarantee migrant women's right to health care. This integrative review describes the communication barriers and facilitators that migrant women encounter to access and use sexual and reproductive health (SRH) services in Europe. METHODS: A literature search was performed to identify original studies in PubMed, CINAHL, PsycINFO, Web of Science, and Scopus, using keywords associated with migrant women and SRH services. This was supplemented by scanning the reference lists from relevant studies and similar reviews. Studies exploring the perspective of migrant women about communication barriers and facilitators to the access and use of SRH services were included, whereas those that solely explored health professional's experiences were excluded. Findings were organized into 4 themes: (1) verbal-linguistic barriers, (2) nonverbal language barriers, (3) cultural barriers, and (4) communication facilitators. RESULTS: Nineteen studies met the inclusion criteria. Results showed that when women had problems understanding or being understood by health professionals, they experienced feelings of anxiety, fear, insecurity, and discrimination that discouraged them from using SRH services. The most requested facilitators by women were health education, access to professional interpreters and translation of written information, and increasing the practitioners' cultural competence. DISCUSSION: Communication barriers undermine migrant women's right to benefit from preventive SRH programs and to make informed decisions concerning their health. It is necessary to establish tailored plans in each health care center to improve intercultural communication that integrate facilitators proposed by women. Future research should provide solid evidence on the effectiveness of each facilitator implemented.


Asunto(s)
Servicios de Salud Reproductiva , Migrantes , Femenino , Humanos , Salud Reproductiva , Accesibilidad a los Servicios de Salud , Lenguaje , Europa (Continente)
9.
Br J Nutr ; 131(5): 901-910, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-37877251

RESUMEN

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP.


Asunto(s)
Selenio , Masculino , Adulto , Humanos , Femenino , Selenoproteína P/metabolismo , Biomarcadores , Antioxidantes , Inglaterra , Glutatión Peroxidasa
10.
Foot Ankle Surg ; 30(2): 117-122, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37949704

RESUMEN

BACKGROUND: Platelet-rich plasma (PRP) and botulinum toxin type A (BTX-A) injections have proven effective in clinical trials for plantar fasciitis treatment but have not been directly compared. We aimed to compare clinical outcomes in patients undergoing PRP or BTX-A injections. METHODS: We performed a randomised controlled trial (59 patients; 1-year follow-up) to assess efficacy, using pain and functional scales (VAS, AOFAS Hindfoot-scale and FAAM questionnaire) and fascia thickness reduction, in control and single ultrasound-guided BTX-A or PRP injection groups. RESULTS: The BTX-A group showed better results at 1-month after treatment. Conversely, the PRP injection was more effective in the long-term, with significant pain reduction and functional improvement. Plantar fascia thickness significantly reduced from months 1 and 3 in the PRP and BTX-A groups, respectively. CONCLUSION: PRP and BTX-A injections are effective in patients with plantar fasciitis with BTX-A achieving better short-term pain reduction and PRP better long-term results. LEVEL OF EVIDENCE: Level I; Randomised Controlled Trial.


Asunto(s)
Toxinas Botulínicas Tipo A , Fascitis Plantar , Plasma Rico en Plaquetas , Humanos , Fascitis Plantar/terapia , Fascitis Plantar/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Dolor , Ultrasonografía Intervencional , Resultado del Tratamiento
11.
Small Methods ; 8(1): e2300930, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37806771

RESUMEN

With the rise of engineered living materials (ELMs) as innovative, sustainable and smart systems for diverse engineering and biological applications, global interest in advancing ELMs is on the rise. Graphene-based nanostructures can serve as effective tools to fabricate ELMs. By using graphene-based materials as building units and microorganisms as the designers of the end materials, next-generation ELMs can be engineered with the structural properties of graphene-based materials and the inherent properties of the microorganisms. However, some challenges need to be addressed to fully take advantage of graphene-based nanostructures for the design of next-generation ELMs. This work covers the latest advances in the fabrication and application of graphene-based ELMs. Fabrication strategies of graphene-based ELMs are first categorized, followed by a systematic investigation of the advantages and disadvantages within each category. Next, the potential applications of graphene-based ELMs are covered. Moreover, the challenges associated with fabrication of next-generation graphene-based ELMs are identified and discussed. Based on a comprehensive overview of the literature, the primary challenge limiting the integration of graphene-based nanostructures in ELMs is nanotoxicity arising from synthetic and structural parameters. Finally, we present possible design principles to potentially address these challenges.


Asunto(s)
Grafito , Nanoestructuras , Grafito/toxicidad , Grafito/química , Nanoestructuras/efectos adversos , Nanoestructuras/química
12.
J Biosoc Sci ; 56(2): 376-390, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37403587

RESUMEN

The aim of this study was to understand the perspectives of female residents of Spain from West Africa in terms of the factors that condition their lives. Pierre Bourdieu's theory and the model of intersectionality formed the framework we used to qualitatively analyse the life stories of these women, which was complemented with life lines. The results showed us that traditional practices such as female genital mutilation and forced marriage are part of the social habitus of this group and they relate to each other through the several types of violence that occurs throughout their lives. In addition, in reference to the African community, these women were no longer African, while in terms of the Spanish community, they did not seem Spanish. At a health, political, and social level, this knowledge can help us to understand this group and to create personalised targeted interventions for them.


Asunto(s)
Migrantes , Humanos , Femenino , Matrimonio , África del Sur del Sahara , España
13.
Percept Mot Skills ; 131(2): 589-611, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38158392

RESUMEN

Recently, the Tactical Assessment Instrument in Football (TAIS) was developed to address football's tactical requirements in terms of game phases, learners' roles, and organizational levels of play. In this study, we sought to evaluate the psychometric properties of this existing instrument in the Physical Education (PE) context and for youth sport teams (ages 8-12 years). Our research design involved: (a) participants playing 37 football games, (b) assessing participants via observation with the TAIS and (c) conducting psychometric analysis on the obtained assessment data. For the psychometric analysis, we carried out our work in four phases: (a) a statistical analysis of the evaluation criteria, (b) analysis of the instrument's structural dimensions, (c) internal item reliability analysis, and (d) provision of evidence for external validity. Participants were 592 children (156 girls, 436 boys; ages 8-12 years) from 74 PE classes or sport teams (from three institutional contexts - schools, community-based sports, and sports clubs) in Spain. We selected 12 tactical criteria and grouped them into four theoretical dimensions (appropriate attack, inappropriate attack, appropriate defense, inappropriate defense) to confirm the instrument's structural dimensions. The Cronbach alpha and Omega McDonald coefficients were greater than .70. The TAIS discriminated between participants from the three institutional contexts, offering evidence of the instrument's external validity. Thus, the TAIS now has sufficient psychometric support for assessing learning of football tactics in PE and youth sport teams. This instrument facilitates an ecological assessment of youth players' understanding of football tactics through four theoretical tactical dimensions and 12 criteria involving information about four learners' roles (both attack and defense, on- and off-the-ball) and three organizational tactical levels of play (whole team, small groups of learners, and individual learners).


Asunto(s)
Fútbol , Deportes Juveniles , Adolescente , Niño , Femenino , Humanos , Masculino , Educación y Entrenamiento Físico , Psicometría , Reproducibilidad de los Resultados
14.
Anal Chim Acta ; 1282: 341841, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37923402

RESUMEN

BACKGROUND: Bodily fluid stains are one of the most relevant evidence that can be found at the crime scene as it provides a wealth of information to the investigators. They help to report on the individuals involved in the crime, to check alibis, or to determine the type of crime that has been committed. They appear as stains in different types of substrates, some of them porous, which can interfere in the analysis. The spectroscopy techniques combined with chemometrics are showing increasing potential for their use in the analysis of such samples due to them being fast, sensitive, and non-destructive. FINDINGS: This is a comprehensive review of the studies that used different spectroscopic techniques followed by chemometrics for analysing biological fluid stains on several surfaces, and under various conditions. It focuses on the bodily fluid stains and the most suitable spectroscopic techniques to study forensic scientific problems such as the substrate's characteristics, the influence of ambient conditions, the aging process of the bodily fluids, the presence of animal bodily fluids and non-biological fluids (interfering substances), and the bodily fluid mixtures. The most widely used techniques were Raman spectroscopy and attenuated total reflection Fourier transform infrared spectroscopy (ATR FTIR). Nonetheless, other non-destructive techniques have been also used, like near infrared hyperspectral imaging (HSI-NIR) or surface enhanced Raman spectroscopy (SERS), among others. This work provides the criteria for the selection of the most promising non-destructive techniques for the effective in situ detection of biological fluid stains at crime scene investigations. SIGNIFICANCE AND NOVELTY: The use of the proper spectroscopic and chemometric approaches on the crime scene is expected to improve the support of forensic sciences to criminal investigations. Evidence may be analysed in a non-destructive manner and kept intact for further analysis. They will also speed up forensic investigations by allowing the selection of relevant samples from occupational ones.


Asunto(s)
Quimiometría , Colorantes , Humanos , Medicina Legal/métodos , Ciencias Forenses/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos
16.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37852877

RESUMEN

OBJECTIVE: To identify a set of indicators to monitor the quality of care for patients with major depression, schizophrenia, or bipolar disorder. METHODS: A group of 10 experts selected the most automatically applicable indicators from a total of 98 identified in a previous study. Five online sessions and 5 discussion meetings were performed to select the indicators that met theoretical feasibility criteria automatically. Subsequently, feasibility was tested in a pilot study conducted in two hospitals of the Spanish Health Service. RESULTS: After evaluating its measurement possibilities in the Spanish Health Service, and the fulfillment of all the quality premises defined, 16 indicators were selected. Three were indicators of major depression, 5 of schizophrenia, 3 of bipolar disorder, and 5 indicators common to all three pathologies. They included measures related to patient safety, maintenance and follow-up of treatment, therapeutic adherence, and adequacy of hospital admissions. After the pilot study, 5 indicators demonstrated potential in the automatic generation of results, with 3 of them related to treatments (clozapine in schizophrenia, lithium for bipolar disorder, and valproate in women of childbearing age). CONCLUSIONS: Indicators support the monitoring of the quality of treatment of patients with major depression, schizophrenia, or bipolar disorder. Based on this proposal, each care setting can draw up a balanced scorecard adjusted to its priorities and care objectives, which will allow for comparison between centers.

17.
Front Immunol ; 14: 1223539, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680635

RESUMEN

Background: Numerous lines of evidence confirm that decidual stromal cells (DSCs) play a key role in maternal-fetal immune tolerance. Under the influence of progesterone and other hormones, the DSCs go through a process of differentiation (decidualization) during normal pregnancy. In mice, DSCs inhibit the expression of chemokines that attract abortigenic Th1 and Tc cells to the decidua. We have studied this phenomenon in humans. Methods: We established human DSC lines and decidualized these cells in vitro with progesterone and cAMP. We determined the expression of the chemokines CXCL9, CXCL10 and CXCL11, whose receptor CXCR3 is expressed by Th1 and Tc cells, in undifferentiated DSCs and decidualized DSCs by qRT-PCR. Activated CD3+CXCR3+ cells, including CD4+ Th1 cells and CD8+ Tc cells, were induced in vitro. The migration capacity of these activated lymphocytes was investigated in Transwell chambers with conditioned media from undifferentiated and decidualized DSCs. Results: We demonstrated that CXCL9 was not expressed by DSCs, whereas the expression of CXCL10 and CXCL11 was inhibited in decidualized cells. Conditioned media from decidualized cells significantly inhibited the migration of Th1 and Tc cells. We found that decidualized cells secrete factors of MW less than 6000-8000 Da, which actively inhibit the chemotaxis of these lymphocytes. Discussion: These results confirm in humans that decidualization of DSCs inhibits the expression by these cells of chemokines that attract Th1 and Tc cells and induces the secretion by DSCs of factors that inhibit the chemotaxis of these lymphocytes, thus preventing the arrival of abortigenic T cells in the decidua.


Asunto(s)
Quimiotaxis , Progesterona , Femenino , Embarazo , Humanos , Animales , Ratones , Medios de Cultivo Condicionados , Feto , Linfocitos T CD8-positivos
18.
Int J Mol Sci ; 24(16)2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37629155

RESUMEN

PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.


Asunto(s)
Neoplasias de la Próstata , Oncología por Radiación , Humanos , Masculino , Reparación del ADN , Oncología Médica , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia
19.
Clin Sci (Lond) ; 137(16): 1333-1346, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37593846

RESUMEN

Weight loss in overweight or obese individuals with Type 2 diabetes (T2D) can normalize hepatic fat metabolism, decrease fatty acid oversupply to ß cells and restore normoglycaemia. One in six people has BMI <27 kg/m2 at diagnosis, and their T2D is assumed to have different aetiology. The Personal Fat Threshold hypothesis postulated differing individual thresholds for lipid overspill and adverse effects on ß-cell function. To test this hypothesis, people with Type 2 diabetes and body mass index <27kg/m2 (n = 20) underwent repeated 5% weight loss cycles. Metabolic assessments were carried out at stable weight after each cycle and after 12 months. To determine how closely metabolic features returned to normal, 20 matched normoglycemic controls were studied once. Between baseline and 12 months: BMI fell (mean ± SD), 24.8 ± 0.4 to 22.5 ± 0.4 kg/m2 (P<0.0001) (controls: 21.5 ± 0.5); total body fat, 32.1 ± 1.5 to 27.6 ± 1.8% (P<0.0001) (24.6 ± 1.5). Liver fat content and fat export fell to normal as did fasting plasma insulin. Post-meal insulin secretion increased but remained subnormal. Sustained diabetes remission (HbA1c < 48 mmol/mol off all glucose-lowering agents) was achieved by 70% (14/20) by initial weight loss of 6.5 (5.5-10.2)%. Correction of concealed excess intra-hepatic fat reduced hepatic fat export, with recovery of ß-cell function, glycaemic improvement in all and return to a non-diabetic metabolic state in the majority of this group with BMI <27 kg/m2 as previously demonstrated for overweight or obese groups. The data confirm the Personal Fat Threshold hypothesis: aetiology of Type 2 diabetes does not depend on BMI. This pathophysiological insight has major implications for management.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/etiología , Índice de Masa Corporal , Sobrepeso , Obesidad/complicaciones , Pérdida de Peso
20.
J Lipid Res ; 64(8): 100413, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37473919

RESUMEN

Alcoholic-related liver disease (ALD) is one of the leading causes of chronic liver disease and morbidity. Unfortunately, the pathogenesis of ALD is still incompletely understood. StARD1 has emerged as a key player in other etiologies of chronic liver disease, and alcohol-induced liver injury exhibits zonal distribution. Here, we report that StARD1 is predominantly expressed in perivenous (PV) zone of liver sections from mice-fed chronic and acute-on-chronic ALD models compared to periportal (PP) area and is observed as early as 10 days of alcohol feeding. Ethanol and chemical hypoxia induced the expression of StARD1 in isolated primary mouse hepatocytes. The zonal-dependent expression of StARD1 resulted in the accumulation of cholesterol in mitochondria and increased lipid peroxidation in PV hepatocytes compared to PP hepatocytes, effects that were abrogated in PV hepatocytes upon hepatocyte-specific Stard1 KO mice. Transmission electron microscopy indicated differential glycogen and lipid droplets content between PP and PV areas, and alcohol feeding decreased glycogen content in both areas while increased lipid droplets content preferentially in PV zone. Moreover, transmission electron microscopy revealed that mitochondria from PV zone exhibited reduced length with respect to PP area, and alcohol feeding increased mitochondrial number, particularly, in PV zone. Extracellular flux analysis indicated lower maximal respiration and spared respiratory capacity in control PV hepatocytes that were reversed upon alcohol feeding. These findings reveal a differential morphology and functional activity of mitochondria between PP and PV hepatocytes following alcohol feeding and that StARD1 may play a key role in the zonal-dependent liver injury characteristic of ALD.


Asunto(s)
Etanol , Hígado , Animales , Ratones , Etanol/farmacología , Hepatocitos , Hígado/metabolismo , Mitocondrias Hepáticas , Estrés Oxidativo
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