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1.
Food Chem ; 462: 141003, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39208735

RESUMEN

Recently, the increasing incidence of malignant melanoma has become a major public health concern owing to its poor prognosis and impact on quality of life. Consuming foods with potent antitumor compounds can help prevent melanoma and maintain skin health. Fucoxanthin (FX), a naturally occurring carotenoid found in brown algae, possesses antitumor properties. However, its bioavailability, safety risks, and in vivo effects and mechanisms against melanoma remain unclear. This research focused on evaluating the safety and prospective antimelanoma impact of simulated gastrointestinal digestion products (FX-ID) on HaCaT and A375 cells.The results indicate that FX-ID exerts negative effects on mitochondria in A375 cells, increases Bax expression, releases Cytochrome C, and activates cleaved caspase-3, ultimately promoting apoptosis. Additionally, FX-ID influences the mitogen-activated protein kinase (MAPK) pathway by enhancing cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) levels, consequently facilitating apoptosis and inflammation without significantly impacting HaCaT cells. These findings provide insight into inhibitory mechanism of FX-ID against melanoma, guiding the development of functional foods for prevention.


Asunto(s)
Apoptosis , Queratinocitos , Melanoma , Xantófilas , Humanos , Melanoma/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Apoptosis/efectos de los fármacos , Xantófilas/farmacología , Xantófilas/química , Línea Celular Tumoral , FN-kappa B/metabolismo , FN-kappa B/genética , Digestión , Modelos Biológicos , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Antineoplásicos/farmacología , Antineoplásicos/química , Phaeophyceae/química , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 3/genética
2.
Int J Pharm ; 665: 124663, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265854

RESUMEN

Elucidation of the role of gut microbiota in the metabolism of orally administered drugs may improve therapeutic effectiveness and contribute to the development of personalized medicine. In this study, ten different artificial gut microbiota (AGM), obtained by culturing fecal samples in a continuous fermentation system, were challenged for their metabolizing capacity on a panel of six glucocorticoids selected from either prodrugs or drugs. Data from metabolic stability assays highlighted that, while the hydrolysis-mediated conversion of prodrugs to drugs represented only a minor metabolic pathway, significant differences in the stability of parent compounds and in their conversion rates to multiple reductive metabolites were obtained for the selected drugs. In the latter case, a taxonomic composition-dependent ability to convert parent drugs to metabolites was observed. Indeed, the artificial microbial communities dominated by the genus Bacteroides showed the maximal conversion of parent glucocorticoids to several metabolites. Furthermore, the effect of drugs on AGM was also evaluated through shallow shotgun sequencing and flow cytometry-based total bacterial cell count highlighting that these drugs can affect both the taxonomic composition and growth performances of the human gut microbiota.

3.
BMC Oral Health ; 24(1): 1043, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232738

RESUMEN

BACKGROUND: Migraine is one of the most common primary headaches worldwide, while toothache is the most common pain in the orofacial region. The association of migraine pain, and oral pain is unknown. This study aims to investigate the association between migraine and dental and gingival pain with the presence of allodynia. METHODS: A questionnaire comprising demographic data with the ID-Migraine (IDM) tool, an Allodynia Symptom Checklist (ASC), and inquiries about pain and sensitivity in the teeth and gums during migraine attacks was administered to the participants and 762 responded the survey. The study classified participants based on the ASC, and the relationship between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks was analyzed. The statistical analyses utilized Chi-square tests and the Fisher-Exact test. RESULTS: Among 762 migraine patients, 430 (56.44%) were classified as allodynia (+), while 332 (43.56%) were classified as allodynia (-) (p < 0.001). Additionally, 285 participants (37.5%) reported experiencing pain and sensitivity in the teeth and gums during migraine attacks, with a significant relationship observed between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks (p < 0.001). CONCLUSION: The findings of this study have important clinical implications. For migraine patients who are non-allodynic, the presence of pain and sensitivity in their teeth and gums during migraine attacks may indicate underlying dental diseases or the need for dental treatment especially root canal treatment. However, for allodynic patients, such symptoms may not necessarily indicate the presence of dental diseases or the need for dental treatment especially root canal treatment. These results underscore the significance of considering the presence of allodynia in the assessment and management of oral symptoms during migraine attacks.


Asunto(s)
Hiperalgesia , Trastornos Migrañosos , Odontalgia , Humanos , Trastornos Migrañosos/complicaciones , Femenino , Masculino , Hiperalgesia/etiología , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Dolor Facial/etiología , Adulto Joven , Sensibilidad de la Dentina
4.
Food Chem ; 463(Pt 2): 141128, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39276546

RESUMEN

To study the alkylresorcinols ability to trap lipid oxidation products in foods, crackers were prepared with either whole grain rye, wheat, spelt, or oat flour, and either sunflower or linseed oil, and were stored for up to 36 days at room temperature. During storage, polyunsaturated fatty acyl chains degraded, malondialdehyde was produced, and alkylresorcinol content decreased. At the end of the storage, alkylresorcinol content in crackers was reduced by 61-78 % and a part of disappeared alkyresorcinols (3-8 %) appeared as malondialdehyde/alkylresorcinol adducts. Formed adducts were unambiguously identified by using synthesized and characterized (NMR, MS) labelled and unlabelled standards, and determined by LC-MS/MS. This ability of alkylresorcinols to trap malondialdehyde, and most likely other lipid oxidation products, might be playing a role in both the reduction of hazardous reactive carbonyls in whole grain foodstuffs and the observed flavor differences between whole and refined grain food products.

5.
J Mass Spectrom Adv Clin Lab ; 33: 43-48, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39279891

RESUMEN

Background: Reference measurement procedures are an essential element in the standardization and comparability of analytical measurement results in laboratory medicine. No LC-MS/MS-based reference measurement procedure for cefepime in serum has been published previously. Materials and methods: An isotope-dilution based two-dimensional LC-MS/MS reference measurement procedure for cefepime concentrations in human serum was developed and tested. The value assignment of unknown samples is based on a defined measurement series validation. Six unknown samples can be measured per series. Pass criteria for the run and the samples were determined empirically based on a performance evaluation. For this purpose, a between-run determination of five runs of the defined measurement series with six cefepime samples was carried out and evaluated. The goal was to define rigorous, realistic target limits and minimize measurement uncertainty. The final defined target limits are used for series-based validation and value assignment. The results for the six unknown samples are provided with the associated measurement uncertainty for this series. Results: The developed and extensively studied measurement procedure for the quantification of cefepime in serum was found to be practicable and fit for its purpose. The between-run mean imprecision of the six cefepime samples was ≤ 2.0 %, for the QCs it was ≤ 2.3 % and the between-run mean inaccuracy of the QCs was within ± 1.1 %. Conclusion: The novel isotope-dilution-LC-MS/MS measurement procedure in accordance to ISO 15193 can be recommended as candidate reference measurement procedure for the value assignment of cefepime concentrations in human serum.

6.
Health Sci Rep ; 7(9): e2309, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39229476

RESUMEN

Background: Pediatric psoriasis accounts for nearly one-third of the global psoriasis burden. Multiple lines of evidence have shown the relationship between Angiotensin-converting enzyme (ACE) Insertion (I)/deletion(D) polymorphism with psoriasis susceptibility, and oxidative stress (OS) in psoriatic patients. However, such studies, particularly on pediatric psoriasis, are scarce in the local setting. Aims: Our study investigated the prevalence of ACE I/D polymorphism and its associations with oxidative stress in pediatric psoriasis patients in Sri Lanka. Methods: Thirty patients were recruited for this study after obtaining ethical clearance. The polymerase chain reaction was used to explore the ACE I/D polymorphism. Serum Nitric Oxide (NO) levels and the Total Antioxidant Capacity (TAC) were measured using the Griess assay and the FRAP assay. Clinical details were obtained from the clinic reports. Results: Female predominance (76.67%) in pediatric psoriasis was reported, while Plaque psoriasis (66.67%) was found to be the most prevalent form. I/D was reported as the predominant genotype (66.67%) while I/I and D/D genotypes were recorded in 23.33% and 10% of patients, respectively. Significantly higher NO levels were observed in I/D patients than in I/I patients but not among other groups. No differences in TAC among ACE genotypes were reported. Conclusion: This pilot study revealed female gender and I/D genotype with increased NO levels as risk factors for pediatric psoriasis in Sri Lanka. However, it is prudent to increase the sample size to further validate the results.

7.
Microbiol Res ; 288: 127884, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39226667

RESUMEN

Synechococcus sp. PCC7002 has been considered as a photosynthetic chassis for the conversion of CO2 into biochemicals through genetic modification. However, conventional genetic manipulation techniques prove inadequate for comprehensive genetic modifications in this strain. Here, we present the development of a genome editing tool tailored for S. PCC7002, leveraging its endogenous type I-D CRISPR-Cas system. Utilizing this novel tool, we successfully deleted the glgA1 gene and iteratively edited the genome to obtain a double mutant of glgA1 and glgA2 genes. Additionally, large DNA fragments encompassing the entire type I-A (∼14 kb) or III-B CRISPR-Cas (∼21 kb) systems were completely knocked-out in S. PCC7002 using our tool. Furthermore, the endogenous pAQ5 plasmid, approximately 38 kb in length, was successfully cured from S. PCC7002. Our work demonstrates the feasibility of harnessing the endogenous CRISPR-Cas system for genome editing in S. PCC7002, thereby enriching the genetic toolkit for this species and providing a foundation for future enhancements in its biosynthetic efficiency.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Genoma Bacteriano , Plásmidos , Synechococcus , Edición Génica/métodos , Synechococcus/genética , Plásmidos/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Eliminación de Gen
8.
F1000Res ; 13: 922, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257448

RESUMEN

Huntingtin encodes a 3144 amino acid protein, with a polyglutamine repeat tract at the N-terminus. Expansion of this repeat tract above a pathogenic threshold of 36 repeats is the causative mutation of Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. Here we have characterized twenty Huntingtin commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.


Asunto(s)
Anticuerpos , Western Blotting , Técnica del Anticuerpo Fluorescente , Proteína Huntingtina , Inmunoprecipitación , Humanos , Proteína Huntingtina/genética , Proteína Huntingtina/inmunología , Inmunoprecipitación/métodos , Técnica del Anticuerpo Fluorescente/métodos , Anticuerpos/inmunología , Animales , Enfermedad de Huntington/inmunología , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/genética , Células HEK293
9.
J Forensic Sci ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233363

RESUMEN

Disaster victim identification (DVI) refers to the forensic identification of unknown individuals following a mass disaster event. Human dental structures can contain viable DNA sources when other soft tissues are compromised. However, labor-intensive sample preparation performed by extensively trained personnel is needed to expose the nuclear material for traditional forensic DNA workflows. With this in mind, we evaluated two simplified sample preparation protocols for processing tooth samples using either a conventional forensic DNA workflow or the Applied Biosystems® RapidHIT™ ID instrument. Briefly, sample sets for both protocols included 10 deciduous teeth that were cleaned prior to either fragmentation with a claw hammer (for RapidHIT™ ID processing) or fine-powder pulverization with a consumer-grade coffee grinder (for traditional workflows). The average percentage of expected STR alleles that were detected above analytical threshold for these tooth samples were comparable between methods: RapidHIT™ ID = 99.0% and GlobalFiler™ = 99.8%. Average intralocus heterozygote peak height ratios (PHRs) were comparable: RapidHIT™ ID = 0.80 and GlobalFiler™ = 0.86. Importantly, 9 of 10 samples analyzed via the RapidHIT™ ID required analyst review for flagged artifact peaks and quality issues. Across all profiles, 91% of alleles passed quality metrics for the RapidHIT™ workflow versus 100% for conventional GlobalFiler™ analysis. Collectively, these results suggest that quick, low-tech tooth sample fragmentation followed by analysis with the RapidHIT™ ID instrument can produce complete STR profiles from aged tooth samples. Future studies should include larger samples sets, more challenging tooth samples, and further simplification of sample preparation to enable field-forward, on-scene DVI.

10.
Equine Vet J ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233387

RESUMEN

BACKGROUND: It is unknown whether short-term transportation affects endocrine responses similarly in horses with and without insulin dysregulation (ID). OBJECTIVES: To characterise the effect of short-term transportation on stress parameters and insulin responses to an oral sugar test (OST) in horses with and without ID. STUDY DESIGN: Longitudinal cohort study. METHODS: Fourteen adult non-pregnant, non-PPID mares of mixed light breeds were grouped as either ID (n = 7) or non-ID (n = 7) based on endocrine testing. Over 2 weeks, horses were transported once, in groups of 3-4 in a horse trailer on a round-trip journey of ~1.5 h. Blood and saliva were collected 24 h and 1 h pre-transportation, directly after unloading and 15 min, 1 h, 3 h plus 24 h post-transportation. An OST was performed 24 h pre-transportation and 3 h post-transportation with a pre- (T0) and post-OST sample collected 60 min later (T60). Heart rates and rectal temperatures were also collected throughout the study. Serum insulin, serum cortisol, and plasma glucose were measured using validated assays. Repeated measures ANOVA were used to determine differences after transportation and between ID and non-ID horses. Non-normal data were log-transformed and multiple comparisons were adjusted using Bonferroni post hoc tests. RESULTS: Mean insulin was higher in ID horses versus non-ID horses (mean = 109.9 µU/mL vs. 30.2 µU/mL, p < 0.001; 95% CI for mean difference = [55.6-107.7 µU/mL]). Mean serum insulin increased following OST at T60 in ID horses pre- (154.6 µU/mL, p = 0.04; 95% CI = [86.3-223.0 µU/mL]) and post-transportation (284.6 µU/mL, p = 0.03; 95% CI = [114.3-454.8 µU/mL]). Non-ID horses had a mean OST T60 insulin post-transportation of 56.6 µU/mL (95% CI = [29.1-84.1 µU/mL]); above recognised threshold [45 µU/mL] for ID diagnosis. MAIN LIMITATIONS: Small number of horses, only mares used, and OST not performed immediately post-transportation. CONCLUSIONS: Performing an OST 3 h following short-term transportation may result in inaccurate ID status.


CONTEXTO: Atualmente não se sabe se o transporte de curto prazo afeta as respostas endócrinas de maneira semelhante em cavalos com e sem disfunção insulinêmica (DI). OBJETIVOS: Caracterizar o efeito do transporte de curto prazo nos parâmetros de estresse e nas respostas de insulina a um teste de açúcar oral (TAO) em cavalos com e sem DI. DELINEAMENTO DO ESTUDO: Estudo de coorte longitudinal. MÉTODOS: Quatorze éguas adultas não prenhes, sem disfunção da pars intermédia da pituitária, de raças leves foram agrupadas como DI (n = 7) ou não­DI (n = 7) com base em testes endócrinos. Durante 2 semanas, as éguas foram transportadas uma vez, em grupos de 3 a 4,em um caminhão de cavalos, em uma viagem de ida e volta de ~1,5 h. Sangue e saliva foram coletados 24 h e 1 h antes do transporte, diretamente após o descarregamento e 15 min, 1 h, 3 h e 24 h após o transporte. Um TAO foi realizado 24 h antes do transporte e 3 h após o transporte, com uma amostra pré­ (T0) e pós­TOA coletada 60 min depois (T60). Frequências cardíacas e temperaturas retais também foram coletadas ao longo do estudo. Insulina sérica, cortisol sérico e glicose plasmática foram medidos usando ensaios validados. ANOVA de medidas repetidas foi utilizada para determinar diferenças após o transporte e entre cavalos com e sem DI. Dados não normais foram transformados logaritmicamente e comparações múltiplas foram ajustadas usando testes post hoc de Bonferroni. RESULTADOS: A média de insulina foi maior em cavalos com DI em comparação aos cavalos sem DI (média = 109,9 µU/mL vs 30,2 µU/mL, p < 0,001; IC 95% para diferença de média = [55,6­107,7 µU/mL]). A média de insulina sérica aumentou após o TAO em T60 em cavalos com DI antes (154,6 µU/mL, p = 0,04; IC 95% = [86,3­223,0 µU/mL]) e após o transporte (284,6 µU/mL, p = 0,03; IC 95% = [114,3­454,8 µU/mL]). Cavalos sem DI tiveram uma média de insulina TAO T60 pós­transporte de 56,6 µU/mL (IC 95% = [29,1­84,1 µU/mL]); acima do limite reconhecido [45 µU/mL] para diagnóstico de DI. PRINCIPAIS LIMITAÇÕES: Pequeno número de cavalos, uso apenas de éguas e TAO não realizado imediatamente após o transporte. CONCLUSÕES: Realizar um TAO 3 horas após o transporte de curto prazo pode resultar em um status de DI impreciso.

11.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39273240

RESUMEN

Gene expression patterns are very sensitive to external influences and are reflected in phenotypic changes. It was previously described that transferring melanoma cells from a plastic surface to Matrigel led to formation of de novo vascular networks-vasculogenic mimicry-that are characteristic to a stemness phenotype in aggressive tumors. Up to now there was no detailed data about the gene signature accompanying this process. Here, we show that this transfer shortly led to extremely strong epigenetic changes in gene expression in the melanoma cells. We observed that on Matrigel numerous genes controlling ribosome biogenesis were upregulated. However, most of the activated genes were inhibitors of the differentiation genes (ID1, ID2, and ID3). At the same time, the genes that control differentiation were downregulated. Both the upregulated and the downregulated genes are simultaneously targeted by different transcription factors shaping sets of co-expressed genes. The specific group of downregulated genes shaping contacts with rDNA genes are also associated with the H3K27me3 mark and with numerous lincRNAs and miRNAs. We conclude that the stemness phenotype of melanoma cells is due to the downregulation of developmental genes and formation of dedifferentiated cells.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Proteína 1 Inhibidora de la Diferenciación , Proteína 2 Inhibidora de la Diferenciación , Proteínas Inhibidoras de la Diferenciación , Melanoma , Melanoma/genética , Melanoma/patología , Melanoma/metabolismo , Humanos , Proteínas Inhibidoras de la Diferenciación/genética , Proteínas Inhibidoras de la Diferenciación/metabolismo , Proteína 2 Inhibidora de la Diferenciación/genética , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Proteína 1 Inhibidora de la Diferenciación/genética , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Línea Celular Tumoral , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Fenotipo , Diferenciación Celular/genética , Epigénesis Genética , Combinación de Medicamentos , Colágeno , Proteoglicanos , Laminina , Proteínas de Neoplasias
12.
F1000Res ; 13: 481, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220380

RESUMEN

Protein-glutamine gamma-glutamyltransferase 2 (TGM2) is a Ca 2+ dependent enzyme that catalyzes transglutaminase cross-linking modifications. TGM2 is involved in various diseases, either in a protective or contributory manner, making it a crucial protein to study and determine its therapeutic potential. Identifying high-performing TGM2 antibodies would facilitate these investigations. Here we have characterized seventeen TGM2 commercial antibodies for western blot and sixteen for immunoprecipitation, and immunofluorescence. The implemented standardized experimental protocol is based on comparing read-outs in knockout cell lines against their isogenic parental controls. This study is part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While the use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.


Asunto(s)
Anticuerpos , Western Blotting , Técnica del Anticuerpo Fluorescente , Inmunoprecipitación , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas , Humanos , Transglutaminasas/inmunología , Técnica del Anticuerpo Fluorescente/métodos , Inmunoprecipitación/métodos , Anticuerpos/inmunología , Proteínas de Unión al GTP/inmunología
13.
J Exp Clin Cancer Res ; 43(1): 222, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39123206

RESUMEN

BACKGROUND: The mechanisms enabling dynamic shifts between drug-resistant and drug-sensitive states in cancer cells are still underexplored. This study investigated the role of targeted autophagic protein degradation in regulating ovarian cancer stem cell (CSC) fate decisions and chemo-resistance. METHODS: Autophagy levels were compared between CSC-enriched side population (SP) and non-SP cells (NSP) in multiple ovarian cancer cell lines using immunoblotting, immunofluorescence, and transmission electron microscopy. The impact of autophagy modulation on CSC markers and differentiation was assessed by flow cytometry, immunoblotting and qRT-PCR. In silico modeling and co-immunoprecipitation identified ID1 interacting proteins. Pharmacological and genetic approaches along with Annexin-PI assay, ChIP assay, western blotting, qRT-PCR and ICP-MS were used to evaluate effects on cisplatin sensitivity, apoptosis, SLC31A1 expression, promoter binding, and intracellular platinum accumulation in ID1 depleted backdrop. Patient-derived tumor spheroids were analyzed for autophagy and SLC31A1 levels. RESULTS: Ovarian CSCs exhibited increased basal autophagy compared to non-CSCs. Further autophagy stimulation by serum-starvation and chemical modes triggered proteolysis of the stemness regulator ID1, driving the differentiation of chemo-resistant CSCs into chemo-sensitive non-CSCs. In silico modeling predicted TCF12 as a potent ID1 interactor, which was validated by co-immunoprecipitation. ID1 depletion freed TCF12 to transactivate the cisplatin influx transporter SLC31A1, increasing intracellular cisplatin levels and cytotoxicity. Patient-derived tumor spheroids exhibited a functional association between autophagy, ID1, SLC31A1, and platinum sensitivity. CONCLUSIONS: This study reveals a novel autophagy-ID1-TCF12-SLC31A1 axis where targeted autophagic degradation of ID1 enables rapid remodeling of CSCs to reverse chemo-resistance. Modulating this pathway could counter drug resistance in ovarian cancer.


Asunto(s)
Autofagia , Resistencia a Antineoplásicos , Proteína 1 Inhibidora de la Diferenciación , Células Madre Neoplásicas , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Proteína 1 Inhibidora de la Diferenciación/genética , Línea Celular Tumoral , Cisplatino/farmacología
14.
J Med Life ; 17(5): 500-507, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-39144687

RESUMEN

The mediator complex subunit 23 (MED23) gene encodes a protein that acts as a tail module mediator complex, a multi-subunit co-activator involved in several cellular activities. MED23 has been shown to have substantial roles in myogenesis and other molecular mechanisms. The functions of MED23 in the neurological system remain unclear and the clinical phenotype is not thoroughly described. Whole exome sequencing was used to identify a novel mutation in the MED23 gene. DNA capture probes using next-generation sequencing-based copy number variation analysis with Illumina array were performed. The clinical, demographic, neuroimaging, and electrophysiological data of the patients were collected, and similarly, the data of all reported cases in the literature were extracted to compare findings. Screening a total of 9,662 articles, we identified 22 main regulatory processes for the MED23 gene, including suppressive activity for carcinogenic processes. MED23 is also involved in the brain's neurogenesis and functions. The identified cases mainly presented with intellectual disability (87.5%) and developmental delay (50%). Seizures were present in only 18.75% of the patients. Slow backgrounds and spike and sharp-wave complexes were reported on the electroencephalogram (EEG) of a few patients and delayed myelination, thin corpus callosum, and pontine hypoplasia on magnetic resonance imaging (MRI). The MED23 gene regulates several processes in which its understanding promotes considerable therapeutic potential for patients. It is crucial to consider genetic and laboratory testing, particularly when encountering potential carriers. Intellectual disability and developmental delay are the most notable clinical signs with heterogeneous features on EEG and MRI.


Asunto(s)
Complejo Mediador , Niño , Femenino , Humanos , Masculino , Variaciones en el Número de Copia de ADN/genética , Electroencefalografía , Secuenciación del Exoma , Genómica/métodos , Discapacidad Intelectual/genética , Complejo Mediador/genética , Mutación/genética , Fenotipo
15.
F1000Res ; 13: 817, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39169954

RESUMEN

Synaptotagmin-1 is a synaptic vesicle transmembrane protein that senses calcium influx via its tandem C2-domains, triggering synchronous neurotransmitter release. Disruption to SYT1 is associated with neurodevelopmental disorders, highlighting the importance of identifying high-quality research reagents to enhance understanding of Synaptotagmin-1 in health and disease. Here we have characterized thirteen Synaptotagmin-1 commercial antibodies for western blot, immunoprecipitation, immunofluorescence and flow cytometry using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.


Asunto(s)
Anticuerpos , Western Blotting , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Inmunoprecipitación , Sinaptotagmina I , Sinaptotagmina I/inmunología , Sinaptotagmina I/metabolismo , Humanos , Citometría de Flujo/métodos , Inmunoprecipitación/métodos , Técnica del Anticuerpo Fluorescente/métodos , Anticuerpos/inmunología
16.
Front Immunol ; 15: 1411352, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161773

RESUMEN

Multiple myeloma (MM) is a hematological cancer marked by plasma cell accumulation in the bone marrow. Despite treatment advancements, MM remains incurable in most patients. MM-associated immune dysregulation fosters disease progression, prompting research into immunotherapy to combat the disease. An area of immunotherapy investigation is the design of myeloma vaccine therapy to reverse tumor-associated immune suppression and elicit tumor-specific immune responses to effectively target MM cells. This article reviews vaccine immunotherapy for MM, categorizing findings by antigen type and delivery method. Antigens include idiotype (Id), tumor-associated (TAA), tumor-specific (TSA), and whole tumor lysate. Myeloma vaccination has so far shown limited clinical efficacy. However, further studies are essential to optimize various aspects, including antigen and patient selection, vaccine timing and sequencing, and rational combinations with emerging MM treatments.


Asunto(s)
Vacunas contra el Cáncer , Mieloma Múltiple , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Humanos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Animales , Antígenos de Neoplasias/inmunología , Inmunoterapia/métodos
17.
Epilepsy Res ; 205: 107427, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39116513

RESUMEN

OBJECTIVE: We described patterns and trends in ED use among adults with epilepsy in the United States. METHODS: Utilizing inpatient and ED discharge data from seven states, we conducted a cross-sectional analysis to identify adult ED visits diagnosed with epilepsy or seizures from 2010 to 2019. Using ED visit counts and estimates of state-level epilepsy prevalence, we calculated ED visit rates overall and by payer, condition, and year. RESULTS: Our data captured 304,935 ED visits with epilepsy as a primary or secondary diagnosis in 2019. Across the seven states, visit rates ranged between 366 and 726 per 1000 and were higher than rates for adults without epilepsy in all states but one. ED visit rates were highest among Medicare and Medicaid beneficiaries (vs commercial or self-pay). Adults with epilepsy were more likely to be admitted as inpatients. Visits for nervous system disorders were 6.3-8.2 times higher among people with epilepsy, and visits for mental health conditions were 1.2-2.6 times higher. Increases in ED visit rates from 2010 to 2019 among people with epilepsy exceeded increases among adults without by 6.0-27.3 percentage points. CONCLUSION: Adults with epilepsy visit the ED frequently and visit rates have been increasing over time. These results underscore the importance of identifying factors contributing to ED use and designing tailored interventions to improve ambulatory care quality.


Asunto(s)
Servicio de Urgencia en Hospital , Epilepsia , Medicaid , Humanos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Estudios Transversales , Epilepsia/epidemiología , Epilepsia/terapia , Masculino , Adulto , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Anciano , Medicaid/estadística & datos numéricos , Adulto Joven , Medicare/estadística & datos numéricos , Adolescente , Aceptación de la Atención de Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Hospitalización/tendencias
18.
Palliat Med Rep ; 5(1): 350-358, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144135

RESUMEN

Background: Identifying patients who require palliative care is a major public health concern. ID-PALL is the first screening instrument developed and validated to differentiate between patients in need of general versus specialized palliative care. Objectives: This study aimed to (1) evaluate user satisfaction and the facilitators and barriers for ID-PALL use and (2) assess the prevalence of patients who require palliative care. Design: A mixed methods study with an explanatory sequential design. Setting/Subjects: Over a six-month period, patients admitted to two internal medicine wards of a Swiss tertiary hospital were screened by nurses and physicians with ID-PALL, two to three days after hospitalization. Nurses and physicians completed a questionnaire and participated in focus groups. Results: Out of 969 patients, ID-PALL was completed for 420 (43.3%). Sixty percent of patients assessed needed general palliative care and 26.7% specialized palliative care. From the questionnaire and focus groups, five subthemes were identified concerning facilitators and barriers: organization, knowledge, collaboration, meaning, and characteristics of the instrument. ID-PALL was recognized as an easy-to-use and helpful instrument that facilitates discussion between health care professionals about palliative care. The difficulties in using ID-PALL in nurse-physician collaboration and the paucity of referrals to the palliative care team were highlighted. Conclusions: ID-PALL helped to identify a very high prevalence of palliative care needs among internal medicine patients in a tertiary hospital setting. Although regarded as helpful and easy to use, challenges remain concerning interprofessional implementation and inclusion of palliative care specialists, which may be met by automatic referrals in case of specialist needs.

19.
Cureus ; 16(7): e64562, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39144842

RESUMEN

BACKGROUND: Home care for children with severe motor and intellectual disabilities (SMID) is challenging for parents because it is highly intensive and long-lasting. The pursuit of happiness is an essential goal for everyone. However, only a few studies have focused on the happiness of families with such children. OBJECTIVE: The study aimed to examine the subjective happiness of parents of children with SMID receiving home care and identify the factors associated with their happiness. METHODS: We conducted a cross-sectional online questionnaire-based survey of 23 parents of children with SMID and nurses with children without disabilities as controls at Tottori University Hospital, Yonago, Japan from July 1 to August 31, 2023. We set the subjective happiness scale (SHS) scores as the outcomes. We used the Mann-Whitney U test to compare the SHS scores between the two groups. Moreover, we extracted the clinical and demographic factors affecting the SHS scores of parents of children with SMID using univariate linear regression analysis. RESULTS: We obtained responses from 12 parents with SMID and 105 controls. The average SHS scores of parents with SMID and controls were 4.8 and 4.7, respectively, and both groups did not differ significantly. Univariate analysis showed that parental male sex and the presence of a tracheostomy were negatively associated with the SHS scores of parents. CONCLUSIONS: The SHS scores did not differ significantly between parents with SMID and controls. However, more attention seemed necessary for fathers and parents of children who have undergone tracheostomies. Given the exploratory nature of this study and its small sample size, larger-scale investigations are warranted. Additionally, qualitative research conducted after establishing trustful relationships could provide further insights.

20.
Exp Dermatol ; 33(8): e15158, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39115029

RESUMEN

S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies.


Asunto(s)
Homeostasis , Proteínas S100 , Piel , Humanos , Proteínas S100/metabolismo , Piel/metabolismo , Piel/patología , Dermatitis/metabolismo , Enfermedades de la Piel/metabolismo , Biomarcadores/metabolismo , Animales
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