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1.
Artículo en Inglés | MEDLINE | ID: mdl-39095337

RESUMEN

PURPOSE: Near real-time patient experience feedback (NRTPEF) can enable a patient-centric, immediate service recovery but has not been widely used in inpatient rehabilitation. We 1) assess the utility, feasibility, and acceptability of implementing a new NRTPEF, perceived by patients and providers; and 2) understand how the NRTPEF became embedded into routine provider practices. MATERIALS AND METHODS: Mixed methods process evaluation of the 8-month implementation of an innovative NRTPEF in an inpatient rehabilitation unit, using interviews and focus groups with all the service-unit leaders and interviews with a randomised sample of patients. Beyond descriptive statistics and content analysis, the Normalisation Process Theory (NPT) informed a framework analysis. RESULTS: Patients and service-unit leaders perceived high utility in the NRTPEF (median: 9 for both; 0-10 scale) and qualitative comments emphasised the value of providing/obtaining timely feedback. The system was found feasible and acceptable for patients (median: 9.5), but with an improvement margin for providers (median: 7.3). Suggestions include strengthening the data-relay format. Even in the pilot form, providers found the NRTPEF became embedded into practice (median 10; average: 8.6). The analysis based on the NPT shows how providers saw differential value, engaged with, and used the patient feedback into reconfigured practices. CONCLUSION: An innovative NRTPEF was found useful, feasible and acceptable, but with refinement opportunities before scale-up.

2.
Stem Cell Res Ther ; 15(1): 223, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044210

RESUMEN

BACKGROUND: Hepatic stellate cells (HSC) have numerous critical roles in liver function and homeostasis, while they are also known for their importance during liver injury and fibrosis. There is therefore a need for relevant in vitro human HSC models to fill current knowledge gaps. In particular, the roles of vitamin A (VA), lipid droplets (LDs), and energy metabolism in human HSC activation are poorly understood. METHODS: In this study, human pluripotent stem cell-derived HSCs (scHSCs), benchmarked to human primary HSC, were exposed to 48-hour starvation of retinol (ROL) and palmitic acid (PA) in the presence or absence of the potent HSC activator TGF-ß. The interventions were studied by an extensive set of phenotypic and functional analyses, including transcriptomic analysis, measurement of activation-related proteins and cytokines, VA- and LD storage, and cell energy metabolism. RESULTS: The results show that though the starvation of ROL and PA alone did not induce scHSC activation, the starvation amplified the TGF-ß-induced activation-related transcriptome. However, TGF-ß-induced activation alone did not lead to a reduction in VA or LD stores. Additionally, reduced glycolysis and increased mitochondrial fission were observed in response to TGF-ß. CONCLUSIONS: scHSCs are robust models for activation studies. The loss of VA and LDs is not sufficient for scHSC activation in vitro, but may amplify the TGF-ß-induced activation response. Collectively, our work provides an extensive framework for studying human HSCs in healthy and diseased conditions.


Asunto(s)
Células Estrelladas Hepáticas , Ácido Palmítico , Factor de Crecimiento Transformador beta , Vitamina A , Humanos , Vitamina A/farmacología , Vitamina A/metabolismo , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/efectos de los fármacos , Ácido Palmítico/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Gotas Lipídicas/metabolismo , Gotas Lipídicas/efectos de los fármacos , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/efectos de los fármacos , Células Madre Pluripotentes/citología , Metabolismo Energético/efectos de los fármacos
3.
Chem Sci ; 15(27): 10612-10624, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38994400

RESUMEN

Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are integral cell surface proteins crucial for the regulation of immune responses and the maintenance of immune tolerance through interactions with sialic acids. Siglecs recognize sialic acid moieties, usually found at the end of N-glycan and O-glycan chains. However, the different Siglecs prefer diverse presentations of the recognized sialic acid, depending on the type of glycosidic linkage used to link to the contiguous Gal/GalNAc or sialic acid moieties. This fact, together with possible O- or N-substitutions at the recognized glycan epitope significantly influences their roles in various immune-related processes. Understanding the molecular details of Siglec-sialoglycan interactions is essential for unraveling their specificities and for the development of new molecules targeting these receptors. While traditional biophysical methods like isothermal titration calorimetry (ITC) have been utilized to measure binding between lectins and glycans, contemporary techniques such as surface plasmon resonance (SPR), microscale thermophoresis (MST), and biolayer interferometry (BLI) offer improved throughput. However, these methodologies require chemical modification and immobilization of at least one binding partner, which can interfere the recognition between the lectin and the ligand. Since Siglecs display a large range of dissociation constants, depending on the (bio)chemical nature of the interacting partner, a general and robust method that could monitor and quantify binding would be highly welcomed. Herein, we propose the application of an NMR-based a competitive displacement assay, grounded on 19F T2-relaxation NMR and on the design, synthesis, and use of a strategic spy molecule, to assess and quantify sialoside ligand binding to Siglecs. We show that the use of this specific approach allows the quantification of Siglec binding for natural and modified sialosides, multivalent sialosides, and sialylated glycoproteins in solution, which differ in binding affinities in more than two orders of magnitude, thus providing invaluable insights into sialoglycan-mediated interactions.

4.
Cells ; 13(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38891108

RESUMEN

Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to protect cells from various environmental changes, and defects in autophagy are linked to cell death. In this sense, decreased autophagy of chondrocytes has been observed in OA articular cartilage. The aim of this work was to study the role of OA mitochondria in apoptosis, autophagy, and senescence, using OA and Normal (N) transmitochondrial cybrids. Results: OA cybrids incubated with menadione showed a higher percentage of late apoptosis and necrosis than N cybrids. Stimulation of cybrids with staurosporine and IL-1ß showed that OA cybrids were more susceptible to undergoing apoptosis than N cybrids. An analysis of the antioxidant response using menadione on gene expression revealed a lower expression of nuclear factor erythroid 2-like 2 and superoxide dismutase 2 in OA than N cybrids. Activation of microtubule-associated protein 1A/1B-light chain 3 was reduced in OA compared to N cybrids. However, the percentage of senescent cells was higher in OA than N cybrids. Conclusion: This work suggests that mitochondria from OA patients could be involved in the apoptosis, autophagy, and senescence of chondrocytes described in OA cartilage.


Asunto(s)
Apoptosis , Autofagia , Senescencia Celular , Condrocitos , Mitocondrias , Osteoartritis , Humanos , Osteoartritis/patología , Osteoartritis/metabolismo , Apoptosis/efectos de los fármacos , Mitocondrias/metabolismo , Condrocitos/metabolismo , Condrocitos/patología , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Factor 2 Relacionado con NF-E2/metabolismo , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Anciano , Interleucina-1beta/metabolismo , Masculino , Persona de Mediana Edad , Vitamina K 3/farmacología , Femenino
5.
PhytoKeys ; 242: 307-316, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903848

RESUMEN

Recent exploratory field expeditions to the western slopes of the Ecuadorian Andes resulted in the discovery of a new species of Amalophyllon (Gesneriaceae). Amalophyllonmiraculum J.L.Clark, sp. nov. is described from two localities in the Centinela region in the Santo Domingo de los Tsáchilas province. The new species is differentiated from congeners by the pendent habit, basal rosette of leaves, leaf blades with deeply serrate margins, and miniature size. Based on IUCN guidelines, a preliminary conservation status is assigned as Critically Endangered (CR).


ResumenRecientes expediciones exploratorias de campo a las laderas occidentales de los Andes ecuatorianos dieron como resultado el descubrimiento de una nueva especie de Amalophyllon (Gesneriaceae). Amalophyllonmiraculum J.L.Clark, sp. nov. se describe de dos localidades de la región de Centinela en la provincia de Santo Domingo de los Tsáchilas. La nueva especie se diferencia de otros congéneres por el hábito colgante, la roseta basal de las hojas, las láminas foliares con márgenes profundamente aserrados y su tamaño en miniatura. Según las directrices de la UICN, se le asigna el estado de conservación preliminar de En Peligro Crítico (CR).

6.
J Orthop Case Rep ; 14(6): 96-100, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38910994

RESUMEN

Introduction: Desmoplastic fibroblastoma is a rare, slow-growing benign soft tissue tumor. It has a wide anatomical distribution and mainly affects adult males. Fourteen percent of cases occur in the ankle or foot. Case Report: In this study, we report a rare location of desmoplastic fibroblastoma on the ankle of a 76-year-old female, discovered as a slowly growing mass. Discussion: Desmoplastic fibroblastoma is an anatomical and clinical entity. It appears macroscopically as a pseudocartilaginous structure and histologically as a stellate or spindle-shaped fibroblastic proliferation in a collagenous stroma. Conclusion: Desmoplastic fibroblastoma has anatomical specificities and should still be clearly distinguished from certain malignant tumors.

7.
J Med Food ; 27(6): 563-574, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38868932

RESUMEN

Antioxidant-related parameters and anti-inflammatory and antimicrobial activities against Listeria monocytogenes were assessed in eight North East Spain poplar propolis samples. Propolis extracts (PEs) were obtained using 70% ethanol (PEE) and methanol (PME). Yield and total phenol compounds were higher in PEE. Phenolic acids were analyzed by a high-performance liquid chromatograph-diode array detector. Caffeic and ferulic acids were quantified in all PEE and PME. All samples contained p-coumaric acid (quantified in 6 PEE and in 3 PME). Ascorbic acid was detected in all propolis, but mainly quantified in PME (≤0.37 mg/g PE). Biological properties were tested on PEE. As for antiradical activities, trolox equivalent antioxidant capacity (TEAC) [against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)•+], ranged between 578 and 4620 µmol trolox/g, 2,2-diphenyl-1-picrylhydrazyl (DPPH) (against DPPH free radical), between 0.049 and 0.094 mg/mL, antioxidant activity against hydroxyl (•OH) radical (AOA), between 0.04 and 11.01 mmol uric acid/g, and oxygen radical absorbance capacity (ORAC) against peroxyl (ROO•) radical between 122 and 3282 µmol trolox/g. Results of TEAC, AOA, and ORAC were significantly correlated. IC50 anti-inflammatory activity ranged from 1.08 to 6.19 mg/mL. Propolis showed higher inhibitory activity against L. monocytogenes CECT934 and L. monocytogenes CP101 by agar well diffusion (P < .05) (10.5 and 10.2 mm, respectively) than against L. monocytogenes CP102 (7.0 mm). Data of this research show that North East Spain propolis may be of interest for pharmaceutical and food industry use.


Asunto(s)
Antiinflamatorios , Antioxidantes , Listeria monocytogenes , Fenoles , Própolis , Própolis/química , Própolis/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Fenoles/análisis , Fenoles/farmacología , Fenoles/química , Listeria monocytogenes/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/análisis , España , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/química
8.
Eur J Obstet Gynecol Reprod Biol ; 299: 173-181, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38878521

RESUMEN

INTRODUCTION AND HYPOTHESIS: Vaginal mesh has been used for years to try to improve the results of pelvic organ prolapse surgery, but current evidence does not confirm this improvement and instead describes serious and frequent adverse events. CLINICAL CASE: 64-year-old patient with rectal extrusion of posterior vaginal mesh placed 8 years earlier, and persistent left ischiorectal fistula refractory to surgery. She required 5 surgeries, carried out jointly between gynecology and general surgery, to solve, firstly, the bilateral perianal abscess secondary to extrusion of the posterior vaginal mesh into the rectum and then the persistent left ischiorectal fistula, despite the removal of the material prosthetic. Finally, the fistula was solved by injection of platelet-rich plasma. CONCLUSIONS: Vaginal mesh complications often need a multidisciplinary approach, and treatment may require multiple approaches and more than one surgical procedure. In the case of a persistent fistula refractory to surgery, after removing the mesh, non-invasive regenerative therapies that promote vascular growth and tissue regeneration could be considered such as platelet-rich plasma.


Asunto(s)
Prolapso de Órgano Pélvico , Fístula Rectal , Mallas Quirúrgicas , Femenino , Humanos , Persona de Mediana Edad , Prolapso de Órgano Pélvico/cirugía , Fístula Rectal/etiología , Fístula Rectal/cirugía , Mallas Quirúrgicas/efectos adversos
9.
Front Bioeng Biotechnol ; 12: 1392575, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933536

RESUMEN

Stem cell-derived islets (SC-islets) are not only an unlimited source for cell-based therapy of type 1 diabetes but have also emerged as an attractive material for modeling diabetes and conducting screening for treatment options. Prior to SC-islets becoming the established standard for disease modeling and drug development, it is essential to understand their response to various nutrient sources in vitro. This study demonstrates an enhanced efficiency of pancreatic endocrine cell differentiation through the incorporation of WNT signaling inhibition following the definitive endoderm stage. We have identified a tri-hormonal cell population within SC-islets, which undergoes reduction concurrent with the emergence of elevated numbers of glucagon-positive cells during extended in vitro culture. Over a 6-week period of in vitro culture, the SC-islets consistently demonstrated robust insulin secretion in response to glucose stimulation. Moreover, they manifested diverse reactivity patterns when exposed to distinct nutrient sources and exhibited deviant glycolytic metabolic characteristics in comparison to human primary islets. Although the SC-islets demonstrated an aberrant glucose metabolism trafficking, the evaluation of a potential antidiabetic drug, pyruvate kinase agonist known as TEPP46, significantly improved in vitro insulin secretion of SC-islets. Overall, this study provided cell identity dynamics investigation of SC-islets during prolonged culturing in vitro, and insights into insulin secretagogues. Associated advantages and limitations were discussed when employing SC-islets for disease modeling.

11.
Acta Physiol (Oxf) ; 240(7): e14156, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38711362

RESUMEN

BACKGROUND: Skeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity-related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1- and 12-months post-SCI. METHODS: To characterize inactivity-related disturbances in spinal cord injury, we studied skeletal muscle cells isolated from SCI subjects. Cell cultures were established from biopsy samples from musculus vastus lateralis from subjects with SCI 1 and 12 months after the injury. The myoblasts were proliferated and differentiated into myotubes before fatty acid and glucose metabolism were assessed and gene and protein expressions were measured. RESULTS: The results showed that glucose uptake was increased, while oleic acid oxidation was reduced at 12 months compared to 1 month. mRNA expressions of PPARGC1α, the master regulator of mitochondrial biogenesis, and MYH2, a determinant of muscle fiber type, were significantly reduced at 12 months. Proteomic analysis showed reduced expression of several mitochondrial proteins. CONCLUSION: In conclusion, skeletal muscle cells isolated from immobilized subjects 12 months compared to 1 month after SCI showed reduced fatty acid metabolism and reduced expression of mitochondrial proteins, indicating an increased loss of oxidative capacity with time after injury.


Asunto(s)
Fibras Musculares Esqueléticas , Traumatismos de la Médula Espinal , Fibras Musculares Esqueléticas/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Humanos , Células Cultivadas , Adulto , Masculino , Oxidación-Reducción , Femenino , Glucosa/metabolismo , Factores de Tiempo , Ácidos Grasos/metabolismo , Metabolismo Energético , Persona de Mediana Edad
12.
Psicol. conduct ; 32(1): 5-40, Abr 1, 2024. tab
Artículo en Español | IBECS | ID: ibc-232220

RESUMEN

El diagnóstico categorial de los trastornos de la personalidad (TTPP) ha sido criticado por diversas razones, entras las que se encuentran el solapamiento de síntomas entre distintos trastornos, su elevada comorbilidad o el carácter dicotómico de su diagnóstico. Estas críticas han llevado al desarrollo de un planteamiento dimensional en las últimas versiones de los sistemas de clasificación, DSM-5/DSM-5-TR y CIE-11, considerando dos aspectos: el funcionamiento de la personalidad y una serie de rasgos patológicos. A pesar de la cuantiosa literatura publicada desde principio de este siglo sobre esta propuesta dimensional, no está claro, a día de hoy, que tenga alguna utilidad clínica. La vaga, abstracta y poco operativizable exposición de lo que constituye el funcionamiento de la personalidad y la compleja y forzada designación de rasgos mayores y menores (facetas) en el DSM-5/DSM-5-TR o sólo mayores y opcionales en la CIE-11, complican el diagnóstico dimensional de los TTPP. En este trabajo se discuten todas estas cuestiones en un intento de aportar algo de luz para un futuro menos sombrío que el actual panorama de los TTPP.(AU)


The categorical diagnosis of personality disorders (PDs) has been criticized forvarious reasons, among which are overlapping of symptoms between differentdisorders, their high comorbidity, and the dichotomous nature of their diagnosis.These criticisms have led to the development of a dimensional approach in thelatest versions of the classification systems, DSM-5/DSM-5-TR and ICD-11,considering two substantial aspects for its new diagnosis: personality functioning,and a series of pathological features. Despite the large amount of literature thathas been published since the beginning of this century on this dimensionalproposal, it is not clear, to date, that this approach enhances clinical utility. Thevague, abstract, and inoperative exposition of what constitutes personalityfunctioning and the complex and forced designation of major and minor traits(facets) in the DSM-5/DSM-5-TR, and only major and optional traits in the ICD-11,complicate, in an unusual way, the dimensional diagnosis of PDs. This paperdiscusses all of these issues in an attempt to shed some light on the potentially darkfuture of the current PDs panorama.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Trastornos de la Personalidad/clasificación , Trastornos de la Personalidad/diagnóstico , Conducta , Psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Clasificación Internacional de Enfermedades
13.
SICOT J ; 10: 11, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38530205

RESUMEN

INTRODUCTION: This study aimed to systematically review the literature and identify the surgical management strategy for fixed flexion contracture in primary total knee arthroplasty (TKA) surgery, pre-, intra-, and post-operatively. Secondary endpoints were etiologies and factors favoring flexion contracture. MATERIALS AND METHODS: Searches were carried out in November 2023 in several databases (Pubmed, Scopus, Cochrane, and Google Scholar) using the following keywords: "flexion contracture AND TKA", "fixed flexion deformity AND TKA", "posterior capsular release AND TKA", "posterior capsulotomy in TKA", "distal femoral resection AND TKA". Study quality was assessed using the STROBE checklist and the Downs and Black score. Data concerning factors or strategies leading to the development or prevention of flexion contracture after TKA were extracted from the text, figures, and tables of the included references. The effect of each predictive factor on flexion contracture after TKA was recorded. RESULTS: Thirty-one studies were identified to meet the inclusion and exclusion criteria. These studies described a variety of preoperative and intraoperative factors that contribute to the development or correction of postoperative flexion contracture. The only clearly identified predictor of postoperative flexion contracture was preoperative flexion contracture. Intraoperative steps described to correct flexion contracture were: soft-tissue balancing (in posterior and medial compartments), distal femoral resection, flexion of the femoral component, and posterior condylar resection. However, no study has investigated these factors in a global model. DISCUSSION: This review identified various pre-, intra-, and post-operative factors predictive of post-operative flexion contracture. In practice, these factors are likely to interact, and it is therefore crucial to further investigate them in a comprehensive model to develop an algorithm for the management of flexion contracture. LEVEL OF EVIDENCE: IV.

14.
Rheol Acta ; 63(3): 205-217, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38440195

RESUMEN

Microrheology with optical tweezers (MOT) is an all-optical technique that allows the user to investigate a materials' viscoelastic properties at microscopic scales, and is particularly useful for those materials that feature complex microstructures, such as biological samples. MOT is increasingly being employed alongside 3D imaging systems and particle tracking methods to generate maps showing not only how properties may vary between different points in a sample but also how at a single point the viscoelastic properties may vary with direction. However, due to the diffraction limited shape of focussed beams, optical traps are inherently anisotropic in 3D. This can result in a significant overestimation of the fluids' viscosity in certain directions. As such, the rheological properties can only be accurately probed along directions parallel or perpendicular to the axis of trap beam propagation. In this work, a new analytical method is demonstrated to overcome this potential artefact. This is achieved by performing principal component analysis on 3D MOT data to characterise the trap, and then identify the frequency range over which trap anisotropy influences the data. This approach is initially applied to simulated data for a Newtonian fluid where the trap anisotropy induced maximum error in viscosity is reduced from ~ 150% to less than 6%. The effectiveness of the method is corroborated by experimental MOT measurements performed with water and gelatine solutions, thus confirming that the microrheology of a fluid can be extracted reliably across a wide frequency range and in any arbitrary direction. This work opens the door to fully spatially and angularly resolved 3D mapping of the rheological properties of soft materials over a broad frequency range.

15.
World J Surg ; 48(4): 855-862, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38353292

RESUMEN

BACKGROUND: Isolated perforations of hollow viscus (HV) represent less than 1% of injuries in blunt abdominal trauma (BAT). When they do present, they are generally due to high-impact mechanisms in the segments of the intestine that are fixed. The aim of this study is to determine the incidence of major HV injuries in BAT at the "Dr. Domingo Luciani" General Hospital (HDL), and address the literature gap regarding updated HV perforations following BAT, especially in low-income settings. METHODS: A retrospective review was conducted on the medical records of patients admitted to our trauma center with a diagnosis of complicated BAT with HV perforation over 14 years. RESULTS AND DISCUSSION: Seven hundred sixty-one patients were admitted under the diagnosis of BAT. Of them, 36.79% underwent emergency surgical resolution, and 6.04% had HV perforation as an operative finding. Almost half (44.44%) of these cases presented as a single isolated injury, while the remaining were associated with other intra-abdominal organ injuries. The most common lesions were Grade II-III jejunum and Grade I transverse colon, affecting an equal proportion of patients at 13.33%. In recent years, an increased incidence of HV injuries secondary to BAT has been observed. Despite this, in many cases, the diagnosis is delayed, so even in the presence of negative diagnostic studies, the surgical approach based on the trauma mechanism, hemodynamic status, and systematic reevaluation of the polytraumatized patient should prevail.


Asunto(s)
Traumatismos Abdominales , Perforación Intestinal , Heridas no Penetrantes , Humanos , Centros Traumatológicos , Heridas no Penetrantes/epidemiología , Heridas no Penetrantes/cirugía , Heridas no Penetrantes/complicaciones , Traumatismos Abdominales/epidemiología , Traumatismos Abdominales/cirugía , Traumatismos Abdominales/complicaciones , Yeyuno , Perforación Intestinal/cirugía , Estudios Retrospectivos
16.
ACS Chem Biol ; 19(2): 483-496, 2024 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-38321945

RESUMEN

Human sialic-acid-binding immunoglobulin-like lectin-9 (Siglec-9) is a glycoimmune checkpoint receptor expressed on several immune cells. Binding of Siglec-9 to sialic acid containing glycans (sialoglycans) is well documented to modulate its functions as an inhibitory receptor. Here, we first assigned the amino acid backbone of the Siglec-9 V-set domain (Siglec-9d1), using well-established triple resonance three-dimensional nuclear magnetic resonance (NMR) methods. Then, we combined solution NMR and molecular dynamic simulation methods to decipher the molecular details of the interaction of Siglec-9 with the natural ligands α2,3 and α2,6 sialyl lactosamines (SLN), sialyl Lewis X (sLeX), and 6-O sulfated sLeX and with two synthetically modified sialoglycans that bind with high affinity. As expected, Neu5Ac is accommodated between the F and G ß-strands at the canonical sialic acid binding site. Addition of a heteroaromatic scaffold 9N-5-(2-methylthiazol-4-yl)thiophene sulfonamide (MTTS) at the C9 position of Neu5Ac generates new interactions with the hydrophobic residues located at the G-G' loop and the N-terminal region of Siglec-9. Similarly, the addition of the aromatic substituent (5-N-(1-benzhydryl-1H-1,2,3-triazol-4-yl)methyl (BTC)) at the C5 position of Neu5Ac stabilizes the conformation of the long and flexible B'-C loop present in Siglec-9. These results expose the underlying mechanism responsible for the enhanced affinity and specificity for Siglec-9 for these two modified sialoglycans and sheds light on the rational design of the next generation of modified sialoglycans targeting Siglec-9.


Asunto(s)
Simulación de Dinámica Molecular , Ácido N-Acetilneuramínico , Humanos , Antígenos de Diferenciación Mielomonocítica/metabolismo , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/metabolismo , Polisacáridos/metabolismo , Espectroscopía de Resonancia Magnética , Ligandos
17.
Adv Healthc Mater ; 13(13): e2303785, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38221504

RESUMEN

Type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD) are epidemiologically correlated disorders with a worldwide growing prevalence. While the mechanisms leading to the onset and development of these conditions are not fully understood, predictive tissue representations for studying the coordinated interactions between central organs that regulate energy metabolism, particularly the liver and pancreatic islets, are needed. Here, a dual pump-less recirculating organ-on-chip platform that combines human pluripotent stem cell (sc)-derived sc-liver and sc-islet organoids is presented. The platform reproduces key aspects of the metabolic cross-talk between both organs, including glucose levels and selected hormones, and supports the viability and functionality of both sc-islet and sc-liver organoids while preserving a reduced release of pro-inflammatory cytokines. In a model of metabolic disruption in response to treatment with high lipids and fructose, sc-liver organoids exhibit hallmarks of steatosis and insulin resistance, while sc-islets produce pro-inflammatory cytokines on-chip. Finally, the platform reproduces known effects of anti-diabetic drugs on-chip. Taken together, the platform provides a basis for functional studies of obesity, T2DM, and MASLD on-chip, as well as for testing potential therapeutic interventions.


Asunto(s)
Islotes Pancreáticos , Dispositivos Laboratorio en un Chip , Hígado , Organoides , Humanos , Hígado/metabolismo , Organoides/metabolismo , Islotes Pancreáticos/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Glucosa/metabolismo
18.
Rev Esp Enferm Dig ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38258758

RESUMEN

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a new entity recently included in the classification of B-cell lymphoproliferative disorders associated with Epstein-Barr virus (EBV). It is related to immunosuppression and it usually appears in the oropharynx or the skin, being the colon an uncommon location. We present the case of a 31-year-old man with ulcerative proctitis being treated with azathioprine (AZA) and adalimumab (ADA), who was admitted to the hospital due to suspicion of a moderate-severe flare of ulcerative proctitis. Microbiological stool analyses were negative, with a positive fecal calprotectin test (2700 mg/kg). Rectoscopy showed severe endoscopic activity, taking multiple biopsies. Intravenous steroids were started at a dose of 60 mg/day. He presented a favorable clinical and analytical evolution, being discharged from the hospital. The histological results were received at gastroenterology consultation, being compatible with EBVMCU. AZA and ADA were withdrawn, whereas descending steroid regimen and oral and topical mesalazine were continued, being the clinical response adequate.

19.
Biomedicines ; 11(11)2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-38001909

RESUMEN

The interplay between skeletal muscle and bone is primarily mechanical; however, biochemical crosstalk by secreted mediators has recently gained increased attention. The aim of this study was to investigate metabolic effects of conditioned medium from osteoblasts (OB-CM) on myotubes and vice versa. Human skeletal muscle cells incubated with OB-CM showed increased glucose uptake and oxidation, and mRNA expression of the glucose transporter (GLUT) 1, while fatty acid uptake and oxidation, and mRNA expression of the fatty acid transporter CD36 were decreased. This was supported by proteomic analysis, where expression of proteins involved in glucose uptake, glycolytic pathways, and the TCA cycle were enhanced, and expression of several proteins involved in fatty acid metabolism were reduced. Similar effects on energy metabolism were observed in human bone marrow stromal cells differentiated to osteoblastic cells incubated with conditioned medium from myotubes (SKM-CM), with increased glucose uptake and reduced oleic acid uptake. Proteomic analyses of the two conditioned media revealed many common proteins. Thus, our data may indicate a shift in fuel preference from fatty acid to glucose metabolism in both cell types, induced by conditioned media from the opposite cell type, possibly indicating a more general pattern in communication between these tissues.

20.
Naturwissenschaften ; 110(6): 52, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37889338

RESUMEN

Anthropogenic land use and climate change are the greatest threats to biodiversity, especially for many globally endangered reptile species. Earth snakes (Conopsis spp.) are a poorly studied group endemic to Mexico. They have limited dispersal abilities and specialized niches, making them particularly vulnerable to anthropogenic threats. Species distribution models (SDMs) were used to assess how future climate and land-cover change scenarios might influence the distribution and habitat connectivity of three earth snakes: Conopsis biserialis (Taylor and Smith), C. lineata (Kennicott), and C. nasus (Günther). Two climate models, CNRM-CM5 (CN) and MPI-ESM-LR (MP) (Representative Concentration Pathway 85), were explored with ENMeval Maxent modelling. Important SDM environmental variables and environmental niche overlap between species were also examined. We found that C. biserialis and C. lineata were restricted by maximum temperatures whereas C. nasus was restricted by minimum ones and was more tolerant to arid vegetation. C. biserialis and C. lineata were primarily distributed in the valleys and mountains of the highlands of the TMBV, while C. nasus was mainly distributed in the Altiplano Sur (Zacatecano-Potosino). C. lineata had the smallest potential distribution and suffered the greatest contraction in the future whereas C. nasus was the least affected species in future scenarios. The Sierra de las Cruces and the Sierra Chichinautzin were identified as very important areas for connectivity. Our results suggest that C. lineata may be the most vulnerable of the three species to anthropogenic and climate changes whereas C. nasus seems to be less affected by global warming than the other species.


Asunto(s)
Biodiversidad , Ecosistema , México , Cambio Climático
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