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1.
Adv Protein Chem Struct Biol ; 141: 299-329, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38960478

RESUMO

TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue.


Assuntos
Metaloproteínas , Humanos , Metaloproteínas/metabolismo , Metaloproteínas/genética , Análise de Célula Única , Autoimunidade , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Animais , Perfilação da Expressão Gênica
3.
Nat Prod Res ; : 1-8, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902957

RESUMO

Two unusual phorbol esters, namely 20-deoxyphorbol-3,4,12-triacetate-13-phenylacetate (1) and phorbol-3,4,12,13-tetraacetate-20-phenylacetate (2) plus ingol-3,8,12-triacetate-7-phenylacetate (3) were isolated from the latex of Euphorbia umbellata and identified by HRESIMS and 2D NMR. Compound 1 is herein described for the first time. Assignment of the phenylacetyl group at C-7 in compound 3 was suggested by the HMBC and NOESY spectra obtained in pyridine-d5. In addition to the latex and its distinct terpenoid fractions, the isolated compounds were tested as latent reversal agents against HIV-1-infected J-Lat cells, with reference to phorbol-12-myristate-13-acetate and ingenol-B. Compound 2 reverted 75-80% the viral latency on the GFP-positive cells, resulting EC50 3.70 µg/mL (SI 6.7), while 1 induced 34-40% reactivation at the same concentration range (4-20 µg/mL). The ingol derivative 3 was ineffective. Phorbol esters were confirmed as effective constituents in the latex since the fraction containing them was 2.4-fold more active than the lyophilised latex at the lowest concentration assayed.

4.
J Anim Breed Genet ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853664

RESUMO

This study utilized Bayesian inference in a genome-wide association study (GWAS) to identify genetic markers associated with traits relevant to the adaptation of Hereford and Braford cattle breeds. We focused on eye pigmentation (EP), weaning hair coat (WHC), yearling hair coat (YHC), and breeding standard (BS). Our dataset comprised 126,290 animals in the pedigree. Out of these, 233 sires were genotyped using high-density (HD) chips, and 3750 animals with medium-density (50 K) single-nucleotide polymorphism (SNP) chips. Employing the Bayes B method with a prior probability of π = 0.99, we identified and tagged single nucleotide polymorphisms (Tag SNPs), ranging from 18 to 117 SNPs depending on the trait. These Tag SNPs facilitated the construction of reduced SNP panels. We then evaluated the predictive accuracy of these panels in comparison to traditional medium-density SNP chips. The accuracy of genomic predictions using these reduced panels varied significantly depending on the clustering method, ranging from 0.13 to 0.65. Additionally, we conducted functional enrichment analysis that found genes associated with the most informative SNP markers in the current study, thereby providing biological insights into the genomic basis of these traits.

5.
Clin Ophthalmol ; 18: 1623-1636, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855013

RESUMO

Background: Retinal detachment is a major postsurgical threat in pediatric cataract surgery; however, the effect of axial length remains unclear. This study aimed to assess the relationship between axial length and detachment risk in vulnerable patients. Methods: This retrospective cohort study analyzed 132 eyes of 84 pediatric cataract surgery patients aged <20 years old. Axial length was measured preoperatively, and the incidence of retinal detachment was recorded over a median follow-up of 4 years. Logistic regression analysis was used to examine the axial length-detachment relationship. Results: Twenty eyes had postoperative retinal detachments. The median axial length was longer in the detachment group (23.6 mm) than in the non-detachment group (21.6 mm). Eyes with axial length ≤23.4 mm had 0.55-fold decreased odds of detachment compared to longer eyes. Preexisting myopia and glaucoma confer heightened risk. Approximately half of the patients retained some detachment risk eight years postoperatively. Conclusion: Shorter eyes (axial length ≤23.4 mm) appear to be protected against pediatric retinal detachment after cataract surgery, whereas myopia, glaucoma, and axial elongation > 23.4 mm elevate the postoperative risk. Understanding these anatomical risk profiles requires surgical planning and follow-up care of children undergoing lensectomy.


This study investigated the protective role of a shorter axial length in preventing retinal detachment after pediatric cataract surgery. This highlights the correlation between smaller eye sizes and reduced detachment risk, emphasizing the need for careful consideration of anatomical factors in surgical planning and patient monitoring, particularly for patients with preexisting myopia or postoperative glaucoma.

7.
J Microbiol Biol Educ ; : e0004024, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771051

RESUMO

Science misinformation represents a significant challenge for the scientific community. Hispanic communities are particularly vulnerable due to language barriers and the lack of accessible information in Spanish. We identified that a key step toward enhancing the accessibility of information for non-native English-speaking communities involves imparting science communication education and training to Hispanic youth. Our goal was to provide them with the skills to become science ambassadors who can effectively engage with their communities and bridge communication gaps. To address this, we developed the first science communication training program in Spanish for Hispanic high school and undergraduate students in Puerto Rico. The program called +Ciencia aims to provide training and education on science communication for Hispanic minorities through experiential and collaborative learning. In the short term, our multifaceted approach works to counter misinformation and promote science literacy within the broader community. Over the long term, our grassroots efforts with students will evolve into a generation of professionals equipped with strong engagement skills and comprehensive training in science communication with a specific focus on Hispanic audiences. Herein, we describe the components of this educational program and provide open access to educational materials and articles developed by three cohorts.

8.
Cureus ; 16(4): e58109, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738022

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive degeneration of motor neurons, resulting in muscle weakness and paralysis. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential marker for monitoring disease severity and progression in ALS, yet longitudinal analyses of NLR are limited. Our study conducts an in-depth examination of NLR dynamics from before diagnosis through the disease's progression to its end stage. We analyze the case of a 56-year-old Puerto Rican male with ALS, tracking his NLR over 13 years - six years before and seven years after his diagnosis - alongside assessments of clinical symptoms and lung function. Our findings indicate that NLR values were initially normal but significantly increased with the onset of symptoms. NLR remained elevated above the normal range, with a notable exception during a period of edaravone therapy when levels normalized. The study demonstrates a clear elevation in NLR associated with ALS progression and critical clinical events, such as symptom onset, diagnosis, and the initiation of respiratory support. This research is, to our knowledge, the first to provide a detailed characterization of NLR changes from the pre-diagnostic phase to end-stage ALS, showing its correlation with clinical deterioration, decreased pulmonary function, and key clinical events. Our results contribute to the body of evidence on NLR's role in ALS while enhancing our understanding of ALS's natural progression.

9.
Cancers (Basel) ; 16(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38792020

RESUMO

Based on the impressive success of Car-T-cell therapy in the treatment of hematological malignancies, a broad application for solid tumors also appears promising. However, some important hurdles need to be overcome. One of these is certainly the identification of specific target antigens on cancer cells. Hypomethylation is a characteristic epigenetic aberration in many tumor entities. Genome-wide screenings for consistent DNA hypomethylations in tumors enable the identification of aberrantly upregulated transcripts, which might result in cell surface proteins. Thus, this approach provides a new perspective for the discovery of potential new Car-T-cell target antigens for almost every tumor entity. First, we focus on this approach as a possible treatment for prostate cancer.

10.
Bioorg Med Chem ; 107: 117756, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38759255

RESUMO

Herein, four silver(I) complexes bearing acetylated d-galactopyranoside-based N-heterocyclic carbene ligands were synthesized and fully characterized by elemental analysis, NMR, and X-ray photoelectron spectroscopy. All complexes were obtained with an anomeric ß-configuration and as monocarbene species. In this study, we investigated the biological effects of the silver(I) complexes 2a-d on the human rhabdomyosarcoma cell line, RD. Our results show concentration-dependent effects on cell density, growth inhibition, and activation of key signaling pathways such as Akt 1/2, ERK 1/2, and p38-MAPK, indicating their potential as anticancer agents. Notably, at 35.5 µM, the complexes induced mitochondrial network disruption, as observed with 2b and 2c, whereas with 2a, this disruption was accompanied by nuclear content release. These results provide insight into the utility of carbohydrate incorporated NHC complexes of silver(I) as new agents in cancer therapy.


Assuntos
Antineoplásicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Rabdomiossarcoma , Prata , Humanos , Acetilação , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Relação Dose-Resposta a Droga , Galactose/química , Galactose/farmacologia , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Metano/química , Metano/análogos & derivados , Metano/farmacologia , Metano/síntese química , Estrutura Molecular , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/patologia , Prata/química , Prata/farmacologia , Relação Estrutura-Atividade
11.
JAMA Oncol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696205

RESUMO

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown. Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR. Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023. Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit. Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points. Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning. Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38704092

RESUMO

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

13.
Cells ; 13(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38607006

RESUMO

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the PCD evaluation and diagnosis framework, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.


Assuntos
Síndrome de Kartagener , Humanos , Algoritmos , Cílios/patologia , Hispânico ou Latino , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética , Microscopia de Vídeo
14.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1559726

RESUMO

La preeclampsia es un trastorno hipertensivo de la gestación que se evidencia durante las últimas semanas de esta. Globalmente, la preeclampsia es la segunda causa de mortalidad materna. Se estima que su incidencia es de aproximadamente un 16% en los países en vías de desarrollo, y llega a superar el 25% en algunos países de Latinoamérica. Se describirán las principales estrategias de prevención de la preeclampsia y su relevancia en el contexto latinoamericano. La búsqueda de información tuvo lugar en PubMed y BVS para las publicaciones realizadas sobre prevención de la preeclampsia, utilizando la expresión de búsqueda (“Disease Prevention” OR “Primary Prevention”) AND (Pre-eclampsia OR Preeclampsia OR “Pre eclampsia”) AND (“Latin America” OR “Central America” OR “South America” OR Caribbean). En PubMed se encontraron 60 y en BVS 42 resultados que responden a la expresión de búsqueda, y fueron seleccionados 18 artículos que discuten estrategias de prevención de la preeclampsia en Latinoamérica. Con estos resultados, se pueden afirmar que, describir las mejores estrategias de prevención de la preeclampsia en Latinoamérica es una tarea pendiente, pues existe una relativa carencia de publicaciones. En consecuencia, se espera que esta revisión motive futuras investigaciones y sea un recurso útil en la actualización médica.


Preeclampsia is a hypertensive disorder of pregnancy that is evident during the last weeks of it. Globally, preeclampsia is the second leading cause of maternal mortality. It is estimated that the incidence is approximately 16% in developing countries, and reaches over 25% in some Latin American countries. The main strategies for the prevention of preeclampsia and their relevance in the Latin American context will be described. The search for information took place in PubMed and BVS for publications on preeclampsia prevention, using the search expression (“Disease Prevention” OR “Primary Prevention”) AND (Pre-eclampsia OR Pre-eclampsia OR “Pre eclampsia”) AND (“Latin America” OR “Central America” OR “South America” OR Caribbean). In PubMed we found 60 and in VHL 42 results that respond to the search expression, and 18 articles were selected that discuss prevention strategies for preeclampsia in Latin America. With these results, it is possible to afirm that describing the best strategies for the prevention of preeclampsia in Latin America is a pending task, since there is a relative lack of publications. Consequently, it is hoped that this review will motivate future research and be a useful resource in medical updating.

15.
Arch Cardiol Mex ; 94(Supl 1): 1-74, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38648647

RESUMO

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications.


La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad.


Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnóstico , Doença Crônica , México
16.
Stem Cell Res Ther ; 15(1): 124, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679735

RESUMO

BACKGROUND: Recombinant human bone morphogenetic protein 2 (rhBMP-2) and human bone marrow mesenchymal stromal cells (hBM-MSCs) have been thoroughly studied for research and translational bone regeneration purposes. rhBMP-2 induces bone formation in vivo, and hBM-MSCs are its target, bone-forming cells. In this article, we studied how rhBMP-2 drives the multilineage differentiation of hBM-MSCs both in vivo and in vitro. METHODS: rhBMP-2 and hBM-MSCs were tested in an in vivo subcutaneous implantation model to assess their ability to form mature bone and undergo multilineage differentiation. Then, the hBM-MSCs were treated in vitro with rhBMP-2 for short-term or long-term cell-culture periods, alone or in combination with osteogenic, adipogenic or chondrogenic media, aiming to determine the role of rhBMP-2 in these differentiation processes. RESULTS: The data indicate that hBM-MSCs respond to rhBMP-2 in the short term but fail to differentiate in long-term culture conditions; these cells overexpress the rhBMP-2 target genes DKK1, HEY-1 and SOST osteogenesis inhibitors. However, in combination with other differentiation signals, rhBMP-2 acts as a potentiator of multilineage differentiation, not only of osteogenesis but also of adipogenesis and chondrogenesis, both in vitro and in vivo. CONCLUSIONS: Altogether, our data indicate that rhBMP-2 alone is unable to induce in vitro osteogenic terminal differentiation of hBM-MSCs, but synergizes with other signals to potentiate multiple differentiation phenotypes. Therefore, rhBMP-2 triggers on hBM-MSCs different specific phenotype differentiation depending on the signalling environment.


Assuntos
Proteína Morfogenética Óssea 2 , Diferenciação Celular , Células-Tronco Mesenquimais , Osteogênese , Proteínas Recombinantes , Humanos , Adipogenia/efeitos dos fármacos , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Condrogênese/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia
17.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612777

RESUMO

High-grade gliomas (HGGs) and glioblastoma multiforme (GBM) are characterized by a heterogeneous and aggressive population of tissue-infiltrating cells that promote both destructive tissue remodeling and aberrant vascularization of the brain. The formation of defective and permeable blood vessels and microchannels and destructive tissue remodeling prevent efficient vascular delivery of pharmacological agents to tumor cells and are the significant reason why therapeutic chemotherapy and immunotherapy intervention are primarily ineffective. Vessel-forming endothelial cells and microchannel-forming glial cells that recapitulate vascular mimicry have both infiltration and destructive remodeling tissue capacities. The transmembrane protein TMEM230 (C20orf30) is a master regulator of infiltration, sprouting of endothelial cells, and microchannel formation of glial and phagocytic cells. A high level of TMEM230 expression was identified in patients with HGG, GBM, and U87-MG cells. In this study, we identified candidate genes and molecular pathways that support that aberrantly elevated levels of TMEM230 play an important role in regulating genes associated with the initial stages of cell infiltration and blood vessel and microchannel (also referred to as tumor microtubule) formation in the progression from low-grade to high-grade gliomas. As TMEM230 regulates infiltration, vascularization, and tissue destruction capacities of diverse cell types in the brain, TMEM230 is a promising cancer target for heterogeneous HGG tumors.


Assuntos
Glioblastoma , Glioma , Doença de Parkinson , Humanos , Glioblastoma/genética , Proteínas de Membrana/genética , Células Endoteliais , Angiogênese , Glioma/genética , Neuroglia , Neovascularização Patológica/genética
18.
Int J Biol Macromol ; 265(Pt 1): 130757, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462107

RESUMO

In this study, an easy and low-cost production method for a cellulose acetate-based gel polymer containing lithium perchlorate and propylene carbonate is described, as well as the investigation of its properties for potential use as an electrolyte in electrochemical devices. Cellulose acetate, a biopolymer derived from natural matrix, is colourless and transparent, as confirmed by the UV-Vis spectroscopy, with 85 % transparency in visible spectrum. The gels were prepared and tested at different concentrations and proportions to optimise their properties. Thermogravimetry, XRD, and FTIR analyses revealed crucial characteristics, including a substantial 90 % mass loss between 150 and 250 °C, a semi-crystalline nature with complete salt dissociation within the polymer matrix, and a decrease in intensity at 1780 cm-1 with increasing Li+ ion concentration, suggesting an improvement in ionic conduction capacity. In terms of electrochemical performance, the gel containing 10 % by mass of cellulose acetate and 1.4 M of LiClO4 emerged as the most promising. It exhibited a conductivity of 2.3 × 10-4 S.cm-1 at 25 °C and 3.0 × 10-4 S.cm-1 at 80 °C. Additionally, it demonstrated an ideal shape of cyclic voltammetry curves and stability after 400 cycles, establishing its suitability as an electrolyte in electrochemical devices.


Assuntos
Celulose/análogos & derivados , Eletrólitos , Polímeros , Condutividade Elétrica
19.
Front Cell Dev Biol ; 12: 1362695, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444829

RESUMO

Gastrulation in zebrafish embryos commences with the morphogenetic rearrangement of blastodermal cells, which undergo a coordinated spreading from the animal pole to wrap around the egg at the vegetal pole. This rearrangement, known as epiboly, relies on the orchestrated activity of maternal transcripts present in the egg, compensating for the gradual activation of the zygotic genome. Epiboly involves the mechano-transducer activity of yap1 but what are the regulators of yap1 activity and whether these are maternally or zygotically derived remain elusive. Our study reveals the crucial role of maternal vgll4a, a proposed Yap1 competitor, during zebrafish epiboly. In embryos lacking maternal/zygotic vgll4a (MZvgll4a), the progression of epiboly and blastopore closure is delayed. This delay is associated with the ruffled appearance of the sliding epithelial cells, decreased expression of yap1-downstream targets and transient impairment of the actomyosin ring at the syncytial layer. Our study also shows that, rather than competing with yap1, vgll4a modulates the levels of the E-cadherin/ß-catenin adhesion complex at the blastomeres' plasma membrane and hence their actin cortex distribution. Taking these results together, we propose that maternal vgll4a acts at epiboly initiation upstream of yap1 and the E-cadherin/ß-catenin adhesion complex, contributing to a proper balance between tissue tension/cohesion and contractility, thereby promoting a timely epiboly progression.

20.
Anim Nutr ; 16: 395-408, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38371472

RESUMO

The present study was to evaluate the effect of trace minerals (Zn, Mn, and Cu) from complexed amino acid minerals (ZMCAA) and bis-glycinate chelated minerals (ZMCGly) in laying hen diets on performance, internal and external egg quality, yolk mineral deposition, intestinal morphometry, and bone characteristics. From 78 to 98 weeks of age, 400 White LSL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per treatment. Treatments were distributed in a 2 × 2 factorial arrangement using either Zn, Mn, and Cu of ZMCAA or ZMCGly source at 2 levels: low (20, 20, and 3.5 mg/kg of Zn, Mn, and Cu, respectively) or high (40, 40, and 7 mg/kg of Zn, Mn, and Cu, respectively). The analysis of variance was performed, and in cases where differences were observed, the means were compared using Tukey's test (P < 0.05). The source and level of trace mineral supplementation had a significant impact on the performance of laying hens. Hens fed ZMCAA had higher egg production (P = 0.01), egg weight (P = 0.02), egg mass (P = 0.01), and lower feed conversion ratio (P = 0.05) compared to those fed ZMCGly. The ZMCAA supplementation showed higher albumen height (P = 0.01), albumen weight (P = 0.01), and eggshell thickness (P < 0.01). The deposition of Zn (P < 0.01), Mn (P < 0.01), and Cu (P < 0.01) in the egg yolk was greater for hens received ZMCAA. Tibia weight (P = 0.04) and bone densitometry (P < 0.01) in the tibia were higher with ZMCAA supplementation. In the small intestine, ZMCAA resulted in longer villi (P = 0.02) and shorter crypt depth (P = 0.01) in the duodenum. Jejunum and ileum measurements were influenced by the level and source of trace minerals (P < 0.05). Laying hens fed ZMCAA exhibited superior performance, egg quality, deposition of trace minerals in the egg yolk, and bone density compared to hens fed ZMCGly. In this study, older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.

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