Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 500
Filtrar
Más filtros

Publication year range
1.
Immunity ; 56(5): 979-997.e11, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-37100060

RESUMEN

Immune cell trafficking constitutes a fundamental component of immunological response to tissue injury, but the contribution of intrinsic RNA nucleotide modifications to this response remains elusive. We report that RNA editor ADAR2 exerts a tissue- and stress-specific regulation of endothelial responses to interleukin-6 (IL-6), which tightly controls leukocyte trafficking in IL-6-inflamed and ischemic tissues. Genetic ablation of ADAR2 from vascular endothelial cells diminished myeloid cell rolling and adhesion on vascular walls and reduced immune cell infiltration within ischemic tissues. ADAR2 was required in the endothelium for the expression of the IL-6 receptor subunit, IL-6 signal transducer (IL6ST; gp130), and subsequently, for IL-6 trans-signaling responses. ADAR2-induced adenosine-to-inosine RNA editing suppressed the Drosha-dependent primary microRNA processing, thereby overwriting the default endothelial transcriptional program to safeguard gp130 expression. This work demonstrates a role for ADAR2 epitranscriptional activity as a checkpoint in IL-6 trans-signaling and immune cell trafficking to sites of tissue injury.


Asunto(s)
Interleucina-6 , ARN , Células Endoteliales/metabolismo , Receptor gp130 de Citocinas , Endotelio/metabolismo , Adenosina Desaminasa/genética , Adenosina Desaminasa/metabolismo
2.
PLoS Pathog ; 20(9): e1012569, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39283943

RESUMEN

Activation of the DNA-sensing STING axis by RNA viruses plays a role in antiviral response through mechanisms that remain poorly understood. Here, we show that the STING pathway regulates Nipah virus (NiV) replication in vivo in mice. Moreover, we demonstrate that following both NiV and measles virus (MeV) infection, IFNγ-inducible protein 16 (IFI16), an alternative DNA sensor in addition to cGAS, induces the activation of STING, leading to the phosphorylation of NF-κB p65 and the production of IFNß and interleukin 6. Finally, we found that paramyxovirus-induced syncytia formation is responsible for loss of mitochondrial membrane potential and leakage of mitochondrial DNA in the cytoplasm, the latter of which is further detected by both cGAS and IFI16. These results contribute to improve our understanding about NiV and MeV immunopathogenesis and provide potential paths for alternative therapeutic strategies.


Asunto(s)
Células Gigantes , Virus del Sarampión , Proteínas de la Membrana , Virus Nipah , Animales , Virus del Sarampión/fisiología , Ratones , Células Gigantes/virología , Células Gigantes/metabolismo , Proteínas de la Membrana/metabolismo , Virus Nipah/fisiología , Sarampión/virología , Sarampión/metabolismo , Sarampión/inmunología , Humanos , Replicación Viral/fisiología , Infecciones por Henipavirus/virología , Infecciones por Henipavirus/metabolismo , Infecciones por Henipavirus/inmunología , Fosfoproteínas/metabolismo , Proteínas Nucleares/metabolismo , Ratones Endogámicos C57BL
3.
J Pathol ; 262(3): 271-288, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38230434

RESUMEN

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Biomarcadores de Tumor/genética , Pronóstico , Fenotipo , Reino Unido , Microambiente Tumoral
4.
J Mol Cell Cardiol ; 193: 53-66, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38838815

RESUMEN

The HSP70 co-chaperone BAG3 targets unfolded proteins to degradation via chaperone assisted selective autophagy (CASA), thereby playing pivotal roles in the proteostasis of adult cardiomyocytes (CMs). However, the complex functions of BAG3 for regulating autophagy in cardiac disease are not completely understood. Here, we demonstrate that conditional inactivation of Bag3 in murine CMs leads to age-dependent dysregulation of autophagy, associated with progressive cardiomyopathy. Surprisingly, Bag3-deficient CMs show increased canonical and non-canonical autophagic flux in the juvenile period when first signs of cardiac dysfunction appear, but reduced autophagy during later stages of the disease. Juvenile Bag3-deficient CMs are characterized by decreased levels of soluble proteins involved in synchronous contraction of the heart, including the gap junction protein Connexin 43 (CX43). Reiterative administration of chloroquine (CQ), an inhibitor of canonical and non-canonical autophagy, but not inactivation of Atg5, restores normal concentrations of soluble cardiac proteins in juvenile Bag3-deficient CMs without an increase of detergent-insoluble proteins, leading to complete recovery of early-stage cardiac dysfunction in Bag3-deficient mice. We conclude that loss of Bag3 in CMs leads to age-dependent differences in autophagy and cardiac dysfunction. Increased non-canonical autophagic flux in the juvenile period removes soluble proteins involved in cardiac contraction, leading to early-stage cardiomyopathy, which is prevented by reiterative CQ treatment.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas Reguladoras de la Apoptosis , Autofagia , Cardiomiopatías , Miocitos Cardíacos , Animales , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiomiopatías/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/deficiencia , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratones , Miocardio/metabolismo , Miocardio/patología , Cloroquina/farmacología , Ratones Noqueados
5.
Liver Transpl ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39352267

RESUMEN

Primary graft dysfunction is a major early complication following liver transplantation, potentially leading to retransplantation or patient death. Coagulation Factor V and ALT have emerged as important biomarkers in assessing liver function, yet their role as early predictors of graft loss has not been fully validated. The aim of this study is to conduct an internal validation of published results on the applicability of Factor V and ALT for diagnosing graft dysfunction and its predictive ability for graft loss within the first 90 days. We conducted a retrospective cohort study including 513 adult recipients from 2012 to 2023 at the Regional University Hospital of Málaga. Factor V and ALT levels were measured on postoperative day 2 and patients were categorized based on FV <37.5 and ALT >1539. The association with 90-day graft loss was analysed. Graft loss occurred in 43 patients (8.4%) within the first 90 days. The combination of FV <37.5 and ALT >1539 on postoperative day 2 demonstrated a specificity of 99% and a test efficiency of 94% in predicting graft loss. Patients meeting both criteria had a 74-fold increased risk of graft loss, with most losses occurring within the first week, and a median survival of 4 days. These findings suggest that Factor V and ALT on postoperative day 2 are reliable early markers for predicting graft loss, enabling risk stratification and guiding critical decisions regarding early retransplantation in the immediate postoperative period.

6.
J Transl Med ; 22(1): 483, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773621

RESUMEN

The Mediterranean Diet (MD) has garnered increasing attention for its potential protective effects against gastric cancer (GC). The MD's rich content of antioxidants, polyphenols, and other bioactive compounds contributes to its ability to modulate gene expression, inhibit tumor growth, and regulate apoptosis. Studies have shown significant reductions in inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) among individuals adhering to the MD, suggesting its pivotal role in mitigating chronic inflammation-associated with cancer development. Furthermore, the MD's anti-angiogenic properties, particularly in components like olive oil, red wine, fish, and tomatoes, offer promising avenues for reducing GC risk by inhibiting tumor angiogenesis. Additionally, the MD's influence on intestinal microbiota composition underscores its potential in maintaining immune homeostasis and reducing systemic inflammation, factors crucial in GC prevention. Despite challenges such as variability in dietary adherence scoring systems and the need for further gender and geographical-specific studies, evidence supports the MD as a cost-effective and holistic approach to GC prevention. Emphasizing the role of nutrition in public health is a promising strategy with broad implications for global health and cancer prevention initiatives. Therefore, this review explores the multifaceted impacts of the MD on GC prevention, delving into its anti-inflammatory, anti-angiogenic, and molecular mechanisms.


Asunto(s)
Dieta Mediterránea , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/prevención & control , Cooperación del Paciente , Inflamación , Microbioma Gastrointestinal
7.
J Transl Med ; 22(1): 949, 2024 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-39427162

RESUMEN

BACKGROUND: Considering differences in body composition and inflammatory status between sexes, as well as recent recommendations advocating for personalized dietary approaches, this study aimed to explore how sex influences weight loss, changes in body composition, and inflammatory status in subjects with grade I and II obesity undergoing a 45-day of the Very Low-Energy Ketogenic Therapy (VLEKT). METHODS: Participants (21 premenopausal females and 21 males), included in the study adhered to the 45-day of the VLEKT and underwent assessments of anthropometric parameters (weight, height, body mass index-BMI -, and waist circumference), body composition via bioelectrical impedance analysis, and inflammatory status measured by high sensitivity C-reactive protein (hs-CRP) levels at baseline and post-intervention. RESULTS: At baseline, premenopausal females and males did not differ in BMI (p = 0.100) and hs-CRP levels (p = 0.948). Males demonstrated overall larger benefits than premenopausal females from the VLEKT in terms of weight loss (Δ% = - 11.63 ± 1.76 vs - 8.95 ± 1.65 kg, p < 0.001), fat mass (Δ% = - 30.84 ± 12.00 vs -21.36 ± 4.65 kg, p = 0.002), and hs-CRP levels (Δ% = - 41.42 ± 21.35 vs - 22.38 ± 17.30 mg/L, p = 0.003). Of interest, in males phase angle values are statistically improved compared to female (Δ% = 17.11 ± 9.00 vs 7.05 ± 3.30°, p < 0.001). CONCLUSION: These findings underscore the importance of considering sex-specific responses in personalized obesity treatment strategies, particularly dietary interventions like VLEKTs.


Asunto(s)
Composición Corporal , Dieta Cetogénica , Inflamación , Pérdida de Peso , Humanos , Femenino , Masculino , Adulto , Inflamación/sangre , Proteína C-Reactiva/metabolismo , Caracteres Sexuales , Índice de Masa Corporal , Obesidad/dietoterapia , Persona de Mediana Edad
8.
Circ Res ; 131(7): 580-597, 2022 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-36000401

RESUMEN

BACKGROUND: ADAR1 (adenosine deaminase acting on RNA-1)-mediated adenosine to inosine (A-to-I) RNA editing plays an essential role for distinguishing endogenous from exogenous RNAs, preventing autoinflammatory ADAR1 also regulates cellular processes by recoding specific mRNAs, thereby altering protein functions, but may also act in an editing-independent manner. The specific role of ADAR1 in cardiomyocytes and its mode of action in the heart is not fully understood. To determine the role of ADAR1 in the heart, we used different mutant mouse strains, which allows to distinguish immunogenic, editing-dependent, and editing-independent functions of ADAR1. METHODS: Different Adar1-mutant mouse strains were employed for gene deletion or specific inactivation of ADAR1 enzymatic activity in cardiomyocytes, either alone or in combination with Ifih1 (interferon induced with helicase C domain 1) or Irf7 (interferon regulatory factor 7) gene inactivation. Mutant mice were investigated by immunofluorescence, Western blot, RNAseq, proteomics, and functional MRI analysis. RESULTS: Inactivation of Adar1 in cardiomyocytes resulted in late-onset autoinflammatory myocarditis progressing into dilated cardiomyopathy and heart failure at 6 months of age. Adar1 depletion activated interferon signaling genes but not NFκB (nuclear factor kappa B) signaling or apoptosis and reduced cardiac hypertrophy during pressure overload via induction of Irf7. Additional inactivation of the cytosolic RNA sensor MDA5 (melanoma differentiation-associated gene 5; encoded by the Ifih1 gene) in Adar1 mutant mice prevented activation of interferon signaling gene and delayed heart failure but did not prevent lethality after 8.5 months. In contrast, compound mutants only expressing catalytically inactive ADAR1 in an Ifih1-mutant background were completely normal. Inactivation of Irf7 attenuated the phenotype of Adar1-deficient cardiomyocytes to a similar extent as Ifih1 depletion, identifying IRF7 as the main mediator of autoinflammatory responses caused by the absence of ADAR1 in cardiomyocytes. CONCLUSIONS: Enzymatically active ADAR1 prevents IRF7-mediated autoinflammatory reactions in the heart triggered by endogenous nonedited RNAs. In addition to RNA editing, ADAR1 also serves editing-independent roles in the heart required for long-term cardiac function and survival.


Asunto(s)
Adenosina Desaminasa , Insuficiencia Cardíaca , Adenosina/metabolismo , Adenosina Desaminasa/genética , Adenosina Desaminasa/metabolismo , Animales , Inosina/metabolismo , Factor 7 Regulador del Interferón/metabolismo , Helicasa Inducida por Interferón IFIH1/genética , Helicasa Inducida por Interferón IFIH1/metabolismo , Interferones/metabolismo , Ratones , Ratones Mutantes , FN-kappa B/metabolismo , ARN
9.
Eur J Clin Microbiol Infect Dis ; 43(5): 1009-1012, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38407691

RESUMEN

Antimicrobial resistance in Neisseria gonorrhoeae (NG) is increasing worldwide. Second-line treatments with macrolides or fluoroquinolones are an option for NG infections in some cases following the STI guideline recommendations. In our study, we compared the gradient diffusion test using EUCAST 2024 breakpoints with a new molecular method using the Allplex™ NG&DR assay (Seegene®) including A2059G/C2611 mutations (23S rRNA) associated with high/moderate-level macrolide resistance and S91F mutation (gyrA) relationship with fluoroquinolone resistance in NG isolates (n = 100). We calculated the sensitivity, specificity, and correlation of the molecular test for fluoroquinolone using the gradient diffusion as the reference method. In twenty-three strains was not detected any mutation associated with macrolides or fluoroquinolone resistance. No A2059G/C2611T mutations were detected, and the S91F mutations were detected in 77 out of the 100 isolates screened. Twenty-three NG isolates were reported to be resistant to azithromycin (ECOFF: >1 mg/L), and 78 NG isolates were resistant to ciprofloxacin (MIC: >0.06 mg/L). The molecular method showed a sensitivity of 96.1% and, a specificity of 90.9% for fluoroquinolone susceptibility, but the statistical analysis between the molecular test and gradient diffusion test was not statistically significant for fluoroquinolone resistance (p = 1). Statistical analysis was not performed for macrolides because of the absence of positive RT-PCR results. According to our data, Allplex™ assay cannot replace the gradient diffusion test for macrolide resistance. However, the assay could be used to test fluoroquinolone resistance in NG isolates as a replacement for phenotypic methods.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Fluoroquinolonas , Gonorrea , Macrólidos , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Fluoroquinolonas/farmacología , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Macrólidos/farmacología , Antibacterianos/farmacología , Humanos , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad Microbiana/métodos , Gonorrea/microbiología , Gonorrea/tratamiento farmacológico , Mutación , Sensibilidad y Especificidad , ARN Ribosómico 23S/genética
10.
Exp Brain Res ; 242(8): 1821-1830, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38847865

RESUMEN

Mentally visualizing objects, understanding relationships between two- or three- dimensional objects, and manipulating objects in space are some examples of visuospatial abilities. Numerous studies have shown that male participants outperform female participants in visuospatial tasks, particularly in mental rotation. One exception is solving jigsaw puzzles. Performance by seven- to eight-year-old girls was found to be superior to that of boys of the same age (Kocijan et al. 2017). No study, however, has confirmed this finding in an adult population, where sex differences are often detectable. Seventy-nine young adult participants were given four different jigsaw puzzles and the Shepard and Metzler mental rotation test (MRT) with two main goals: First, to investigate possible sex differences in jigsaw puzzle solving, and second, to explore a potential relationship between mental rotation and jigsaw puzzle solving. We hypothesized that female participants would outperform males in the jigsaw puzzles but males would outperform females in the MRT. The findings confirmed this hypothesis. Notably, the male performance in jigsaw puzzle solving was attributed to their sex and mediated by their higher MRT scores. These results yielded two key insights. First, they indicate a dissociation between these two visuospatial abilities, jigsaw puzzle solving and mental rotation; and second, female and male participants capitalize on their distinct cognitive strengths when solving visuospatial tasks.


Asunto(s)
Solución de Problemas , Caracteres Sexuales , Percepción Espacial , Humanos , Femenino , Masculino , Percepción Espacial/fisiología , Adulto Joven , Adulto , Solución de Problemas/fisiología , Rotación , Adolescente , Cognición/fisiología , Imaginación/fisiología
11.
Nature ; 557(7706): 516-521, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29769717

RESUMEN

Chromatin remodelling factors (CHRs) typically function to alter chromatin structure. CHRs also reside in ribonucleoprotein complexes, but little is known about their RNA-related functions. Here we show that CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE). CHR2 promotes the transcription of primary microRNA precursors (pri-miRNAs) while repressing miRNA accumulation in vivo. Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity. CHR2 can directly bind to and unwind pri-miRNAs and inhibit their processing, and this inhibition requires the remodelling and helicase activity of CHR2 in vitro and in vivo. Furthermore, the secondary structures of pri-miRNAs differed between wild-type Arabidopsis thaliana and chr2 mutants. We conclude that CHR2 accesses pri-miRNAs through SE and remodels their secondary structures, preventing downstream processing by DCL1 and HYL1. Our study uncovers pri-miRNAs as a substrate of CHR2, and an additional regulatory layer upstream of Microprocessor activity to control miRNA accumulation.


Asunto(s)
Adenosina Trifosfatasas/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , MicroARNs/biosíntesis , Proteínas de Unión al ARN/metabolismo , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , MicroARNs/genética , MicroARNs/metabolismo , Unión Proteica , Pliegue del ARN , Procesamiento Postranscripcional del ARN , Transcripción Genética
12.
Environ Res ; 263(Pt 2): 120086, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39353529

RESUMEN

Infertility is recognized as a multifaceted condition affecting approximately 15% of couples globally, influenced by various factors including genetic predisposition and environmental exposures. Among these environmental factors, bisphenol A (BPA) emerges as a prominent Endocrine-disrupting chemical (EDCs) widely distributed, leading to chronic human exposure in daily life. As regulations on BPA became more stringent, alternative substances such as bisphenol S (BPS) and bisphenol F (BPF) have emerged. Animal studies have demonstrated a dose-dependent decline in fertility and embryotoxicity following chronic exposure to BPA. However, literature data on human studies are limited and heterogeneous. Additionally, even less is known about the relationship between exposure to the BPA analogues (BPS and BPF) and sperm quality. Therefore, the present study aimed to examine the association between urinary concentrations of BPA, BPF, and BPS and semen quality parameters among 195 adult Spanish men from the Led-Fertyl study cohort using multiple linear regression models adjusted by potential confounding variables. Our results revealed an inverse association between log-transformed creatinine-adjusted concentration (ng/mg) of BPA and BPF levels and the percentage of sperm vitality (ß: 3.56 %; 95%CI: 6.48 to -0.63 and ß: 4.14 %; 95%CI: 6.97 to -1.31; respectively). Furthermore, participants in the highest quartile of BPA and BPF urinary concentration exhibited lower sperm vitality compared to those in the lowest quartile (ß: 6.90 %; 95%CI: 11.60 to -2.15 and ß: 9.68 %; 95%CI: 14.43 to -4.94; respectively). These results supply epidemiological evidence establishing a relationship between bisphenols urine exposure and sperm quality, suggesting that a re-evaluation of the overall safety of BPA alternatives is warranted.

13.
J Ultrasound Med ; 43(8): 1489-1499, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38708914

RESUMEN

OBJECTIVES: To investigate the role of high-resolution ultrasound (HR-US) in the initial and differential diagnosis of the Odontogenic Cutaneous Sinus Tract (OCST) in a multicentric setting. METHODS: Skin HR-US examinations of OCSTs performed between January 2019 and June 2023 at different Institutions were retrospectively reviewed. Epidemiological and clinical data (age, gender, location of the skin lesion, causative tooth, and the clinical suspicion) as well as HR-US imaging findings (morphology and length of the sinus tract, Doppler signal, and cortical bone interruption of maxilla or mandible) were collected. US examinations were performed by expert radiologists using a high-performance US scanner, employing a high-frequency linear probe (15 MHz or higher frequencies). In only one patient the HR-US exam was integrated with strain elastography (SE). RESULTS: Sixteen patients were enrolled with a median age of 37.6 years (range 16-70 years). The most frequent clinical suspicion was epidermal cyst, while OCST was suspected in only two cases. In all cases, HR-US depicted the sinus tract as a nodular, triangular or "champignon-shaped" lesion in the subcutaneous layer, which continued with a slightly tortuous band structure, up to the focally interrupted cortical bone plate. Furthermore, color Doppler evaluation showed color signals around and/or within the lesion, expression of inflammation. On SE, the sinus tract showed a hard pattern, due to fibrous and granulomatous tissue. CONCLUSIONS: HR-US, thanks to its high spatial resolution, allows the evaluation of OCST, and play a crucial diagnostic role, mainly when the clinical suspicious is different.


Asunto(s)
Ultrasonografía , Humanos , Masculino , Femenino , Adolescente , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Adulto Joven , Anciano , Ultrasonografía/métodos , Diagnóstico Diferencial , Quistes Odontogénicos/diagnóstico por imagen , Fístula Cutánea/diagnóstico por imagen
14.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39201365

RESUMEN

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice. Our results revealed that the absence of leptin increased lipid storage in the liver and induced significant mitochondrial alterations, which were ultimately responsible for defective ATP production and reactive oxygen species overproduction. Moreover, leptin deficiency promoted mitochondrial biogenesis, fusion, and outer membrane permeabilization. Melatonin treatment reduced the bioenergetic deficit found in ob/ob mice, alleviating some mitochondrial alterations in the electron transport chain machinery, biogenesis, dynamics, respiration, ATP production, and mitochondrial outer membrane permeabilization. Given the role of melatonin in maintaining mitochondrial homeostasis, it could be used as a therapeutic agent against adipogenic steatosis.


Asunto(s)
Leptina , Metabolismo de los Lípidos , Melatonina , Mitocondrias Hepáticas , Animales , Melatonina/farmacología , Leptina/metabolismo , Leptina/deficiencia , Ratones , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Especies Reactivas de Oxígeno/metabolismo , Adenosina Trifosfato/metabolismo , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Metabolismo Energético/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados
15.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38338718

RESUMEN

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.


Asunto(s)
Proteína con Dominio Pirina 3 de la Familia NLR , Sarcopenia , Humanos , Anciano , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Sarcopenia/etiología , Caspasa 1/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Músculo Esquelético/metabolismo
17.
Exp Brain Res ; 241(1): 175-186, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36414752

RESUMEN

It has long been assumed that an accurate representation of the size and shape of one's body is necessary to successfully interact with the environment. Previous research has shown accurate representations when healthy participants make overt judgments (i.e. explicit) about the size of their bodies. However, when body size is judged implicitly, studies have shown systematic distortions. One suggestion for these differences, is that explicit and implicit representations are informed by different sensory modalities. Explicit representations rely on vision whereas implicit representations are informed by haptics. We designed an experiment to investigate if explicit representations that are informed by haptics are more like implicit representation featuring systematic distortions. We asked female participants to estimate the size of their fingers and hands in three different tasks: an explicit-haptic, an implicit, and an explicit-vision task. The results showed that all three representations were distorted and furthermore, the distortions for each representation were different from one another. These results suggest that inaccurate finger and hand length are a stereotypical feature of body representation that is present in both visual and haptic domains. We discuss the results in relation to theories of body representation.


Asunto(s)
Dedos , Mano , Humanos , Adulto , Femenino , Imagen Corporal , Juicio , Tamaño Corporal
18.
J Pediatr Hematol Oncol ; 45(6): e671-e677, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37314943

RESUMEN

The outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer pediatric patients was initially uncertain. The objective of this study was to describe the characteristics and outcome of cancer patients and hematopoietic stem cell transplant recipients from 0 to 19 years with detectable SARS-CoV-2 from April 23, 2020, to April 30, 2022, treated in a tertiary-level hospital in Argentina. A total of 348 cases were registered in 339 patients. The median age was 89.5 (3 to 224) months. The sex was predominantly male: 193 (55.5%). The most common malignant disease was leukemia (42.8%). One hundred four cases (29.9%) had comorbidities. Of the 346 cases with an available blood count, 17.6% had a lymphocyte count <300/mm 3 . Fever was the most common symptom. In most cases (93.1%) presented asymptomatic or mild disease. Twenty-one cases (6%) presented severe or critical status. Eleven of 24 admissions to the intensive care unit were due to COVID-19 (coronavirus disease 2019). Eight patients (2.3%) died. Two deaths were attributable to SARS-CoV-2 (0.6%). Being older, having fever, lymphopenia at diagnosis, and having received hematopoietic stem cell transplant were associated with a more severe disease. Around 90% of the children continued their cancer treatment without any change.


Asunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Humanos , Masculino , Niño , Anciano de 80 o más Años , Femenino , COVID-19/epidemiología , SARS-CoV-2 , Centros de Atención Terciaria , Argentina/epidemiología , Neoplasias/epidemiología , Neoplasias/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos
19.
Dermatology ; 239(2): 277-282, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36122570

RESUMEN

BACKGROUND: Pain is not a trivial issue for hidradenitis suppurativa (HS) patients and has been considered a domain in the Core Outcome Set. To date, there is no evidence about pain caused by the ultrasound examinations. OBJECTIVE: The aim of the study was to assess the presence of pain generated by the ultrasound examinations of HS patients. METHODS: A multicentric cross-sectional study for detecting pain during the ultrasound examinations of HS patients using a validated verbal questionnaire immediately after the imaging studies. Statistical analysis included demographic data and possible associations with sex, age, location, clinical (Hurley), and ultrasonographic scoring (SOS-HS). The statistical tests were two proportions Z test, χ2 test, Student's t test, and ANOVA. A p < 0.05 was considered significant. RESULTS: 317 patients met the criteria. 77.3% of them did not present pain. Of cases with pain, 59.8% were mild, 16.7% moderate, and 23.6% severe. No significant association was found with sex, age, staging, location, or the number of affected regions. Although nonsignificant, severe pain cases were more frequent in the clinical Hurley III and ultrasonographic SOS-HS III stages. CONCLUSION: Pain generated by the ultrasound examination of HS patients is infrequent.


Asunto(s)
Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/diagnóstico por imagen , Estudios Transversales , Índice de Severidad de la Enfermedad , Ultrasonografía/efectos adversos , Dolor/diagnóstico por imagen , Dolor/etiología
20.
Tob Control ; 32(3): 323-329, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-34607886

RESUMEN

INTRODUCTION: The extent of the population's exposure to tobacco imagery across all genres of regular TV programming and the contribution of each of these genres is unknown, except for UK broadcast channels. The objective of this study is to estimate the exposure of young people to tobacco imagery on Chilean prime-time television and the programme source contributing to such exposure. METHODS: Programmes aired during 3 weeks in 2019 from the 15 highest audience channels in Chile were content-analysed for the occurrence of tobacco categorised as actual use, implied use, tobacco paraphernalia, tobacco brand appearances and whether they violated Chilean smoke-free law for each 1 min interval (92 639). The exposure of young people to tobacco content was estimated using media viewership figures. RESULTS: Young people received 29, 11 and 4 million tobacco impressions of any type, explicit use and smoke-free violation, respectively, at a rate of 21.8, 8.0 and 2.1 thousand impressions per hour of TV viewing. The main sources of exposure to tobacco impressions were feature films and animated productions, which were almost entirely non-Chilean. Finally, young people were exposed to tobacco brand impressions primarily through films, effectively circumventing the advertising ban in Chile. DISCUSSION: Television programming is a source of significant youth exposure to tobacco imagery, including branding impressions. To conform to the WHO FCTC, Chile should prohibit tobacco branding in any TV programme and require strong anti-tobacco advertisements prior to any TV programme portraying tobacco.


Asunto(s)
Nicotiana , Productos de Tabaco , Adolescente , Humanos , Televisión , Publicidad , Películas Cinematográficas
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda