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1.
Cureus ; 16(10): e70732, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39493017

RESUMEN

Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic condition characterized by hyperglycemia, which can lead to various microvascular complications, including diabetic nephropathy, neuropathy, and retinopathy. Identifying reliable biomarkers for early detection and risk stratification of these complications is crucial for improving patient outcomes. Adenosine deaminase (ADA) and HbA1c have emerged as potential markers associated with immune function, inflammation, and long-term glycemic control. This study investigates the correlation between ADA and HbA1c levels and microvascular complications in patients with T2DM. Material and methods This prospective observational cross-sectional study involved 150 patients diagnosed with T2DM, focusing on those with diabetic nephropathy, neuropathy, and retinopathy. Clinical data were collected through patient interviews, clinical examinations, and laboratory tests, including measurements of fasting blood glucose, HbA1c, serum creatinine, ADA levels, and urine protein creatinine ratio (UPCR). Fundus examinations and nerve conduction velocity (NCV) tests were performed to assess diabetic retinopathy and neuropathy, respectively. Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, New York), with statistical tests to evaluate the correlation between ADA and HbA1c levels and microvascular complications. Results The study found a significant correlation between elevated ADA and HbA1c levels and microvascular complications in patients with T2DM. Higher ADA levels were particularly associated with diabetic nephropathy (p=0.003), while HbA1c levels showed a positive correlation with all three complications: nephropathy, neuropathy, and retinopathy. The findings suggest that ADA and HbA1c levels can serve as valuable biomarkers for identifying patients at higher risk of developing these complications. Conclusion This study highlights the potential of ADA and HbA1c as biomarkers for early detection and risk assessment of microvascular complications in T2DM patients. Routine monitoring of these markers could improve the management and prognosis of diabetic patients by enabling timely interventions to prevent or mitigate the progression of complications. Further research is needed to explore the underlying mechanisms linking ADA with diabetic complications and to validate its clinical utility.

2.
Cell Rep ; 43(11): 114899, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39441717

RESUMEN

Although adenosine deaminase 2 (ADA2) is considered an extracellular ADA, evidence questions the physiological relevance of this activity. Our study reveals that ADA2 localizes within the lysosomes, where it is targeted through modifications of its glycan structures. We show that ADA2 interacts with DNA molecules, altering their sequences by converting deoxyadenosine (dA) to deoxyinosine (dI). We characterize its DNA substrate preferences and provide data suggesting that DNA, rather than free adenosine, is its natural substrate. Finally, we demonstrate that dA-to-dI editing of DNA molecules and ADA2 regulate lysosomal immune sensing of nucleic acids (NAs) by modulating Toll-like receptor 9 (TLR9) activation. Our results describe a mechanism involved in the complex interplay between NA metabolism and immune response, possibly impacting ADA2 deficiency (DADA2) and other diseases involving this pathway, including autoimmune diseases, cancer, or infectious diseases.

3.
Luminescence ; 39(10): e4930, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39401986

RESUMEN

Phototheranostics with near-infrared fluorescence and reactive oxygen species generation ability and high photothermal conversion efficiency (PCE) plays a significant role in fluorescence imaging-guided synergetic photodynamic and photothermal therapy of tumors. Here, a star molecule in organic photovoltaic materials, NCBDT-4C with an A-D-A conjugated structure, was assembled with DSPE-PEG-NH2 to prepare water dispersive nanoparticles (NPs). The prepared NCBDT-4Cl NPs exhibited a maximum NIR absorption peak at 764 nm and a maximum fluorescence peak at 798 nm. These NPs could generate superoxide anion, singlet oxygen (1O2), and heat under 808 nm laser irradiation. The 1O2 generation quantum yield and PCE of the NPs were 37.5% and 53.6%, respectively. The combination of photodynamic and photothermal therapy of cancer was demonstrated in vitro and in vivo. This work presents the advanced application of organic photovoltaic materials in cancer phototherapy.


Asunto(s)
Rayos Infrarrojos , Imagen Óptica , Fotoquimioterapia , Terapia Fototérmica , Animales , Humanos , Ratones , Nanopartículas/química , Nanomedicina Teranóstica , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Estructura Molecular , Ratones Endogámicos BALB C , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Supervivencia Celular/efectos de los fármacos , Oxígeno Singlete/química , Oxígeno Singlete/metabolismo
4.
Gels ; 10(10)2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39451302

RESUMEN

Injectable, in situ-forming hydrogels, both biocompatible and biodegradable, have garnered significant attention in tissue engineering due to their potential for creating adaptable scaffolds. The adaptability of these hydrogels, made from natural proteins and polysaccharides, opens up a world of possibilities. In this study, sodium alginate was used to synthesize alginate di-aldehyde (ADA) through periodate oxidation, resulting in a lower molecular weight and reduced viscosity, with different degrees of oxidation (54% and 70%). The dual-crosslinking mechanism produced an injectable in situ hydrogel. Initially, physical crosslinking occurred between ADA and borax via borax complexation, followed by chemical crosslinking with gelatin through a Schiff's base reaction, which takes place between the amino groups of gelatin and the aldehyde groups of ADA, without requiring an external crosslinking agent. The formation of Schiff's base was confirmed by Fourier-transform infrared (FT-IR) spectroscopy. At the same time, the aldehyde groups in ADA were characterized using FT-IR, proton nuclear magnetic resonance (¹H NMR), and gel permeation chromatography (GPC), which determined its molecular weight. Furthermore, borax complexation was validated through boron-11 nuclear magnetic resonance (¹¹B NMR). The hydrogel formulation containing 70% ADA, polyethylene glycol (PEG), and 9% gelatin exhibited a decreased gelation time at physiological temperature, attributed to the increased gelatin content and higher degree of oxidation. Rheological analysis mirrored these findings, showing a correlation with gelation time. The swelling capacity was also enhanced due to the increased oxidation degree of PEG and the system's elevated gelatin content and hydrophilicity. The hydrogel demonstrated an average pore size of 40-60 µm and a compressive strength of 376.80 kPa. The lower molecular weight and varied pH conditions influenced its degradation behavior. Notably, the hydrogel's syringeability was deemed sufficient for practical applications, further enhancing its potential in tissue engineering. Given these properties, the 70% ADA/gelatin/PEG hydrogel is a promising candidate and a potential game-changer for injectable, self-crosslinking applications in tissue engineering. Its potential to revolutionize the field is inspiring and should motivate further exploration.

5.
J Clin Med ; 13(20)2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-39458206

RESUMEN

Background: Several GLP-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes (T2DM). Their cardio- and renal-protective effects and their association with substantial weight loss have been evident and progressively expanded their role in the American Diabetes Association (ADA) guidelines, which are endorsed by the European Association for the Study of Diabetes (EASD). The increased demand led to a global shortage. Methods: We utilized a repeated cross-sectional design, drawing data from national prescribing databases, to analyze six GLP-1 RAs: Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Semaglutide, and Tirzepatide. AutoRegressive Integrated Moving Average (ARIMA) models with exogenous variables were applied to assess the trends over time and in different regions. Results: The prescription rates significantly differ between regions. Wales shows the highest prescribing rate for most GLP-1 RAs. The ARIMA models indicated a significant increase in their prescribing rates after the release of the 2022 ADA guidelines (e.g., Dulaglutide: Post-ADA effect of 15.22, 95% CI: [12.97, 17.47]). Following the GLP-1 RA shortages in July 2023, the prescribing rates, particularly for Semaglutide, increased (Shortage effect: 74.36, 95% CI: [71.92, 76.80]). Model diagnostics, including the Akaike Information Criterion (AIC) and Durbin-Watson statistics, confirmed the robustness of these trends. Conclusions: Informed decisions should be made by considering the prescribing trends before and after important events such as the issuing of new guidelines or safety alerts.

6.
Adv Rheumatol ; 64(1): 79, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385260

RESUMEN

Systemic vasculitis is a group of rare diseases that share an essential characteristic: inflammation of blood vessel walls. This injury occurs during the disease course, but specific features vary for each entity. In this paper, we will address relevant aspects of the newest monogenic mutation vasculitis, such as deficiency of adenosine deaminase 2 (ADA2) and VEXAS syndrome (UBA1), and other relevant vasculitis, such as Cogan syndrome and Susac syndrome that may share some similarities with them.


Asunto(s)
Adenosina Desaminasa , Enfermedades Raras , Humanos , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Síndrome de Cogan/complicaciones , Síndrome de Susac/complicaciones , Síndrome de Susac/diagnóstico , Vasculitis Sistémica/diagnóstico , Agammaglobulinemia/complicaciones , Mutación , Vasculitis , Péptidos y Proteínas de Señalización Intercelular
7.
Clin Immunol ; 269: 110394, 2024 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-39481740

RESUMEN

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease characterised by early onset stroke, recurrent fever, and diverse vascular pathologies, caused by loss-of-function homozygous or compound heterozygous variants of ADA2. This research aimed to determine the carrier frequency and expected incidence of DADA2 in China, using massive exome sequencing (ES) data. A total of 50 likely pathogenic/pathogenic variants (LP/PVs) were identified among 69,413 Chinese individuals, including 20 novel and rare variants (<0.0022 % allele frequency), expanding the known spectrum of PVs in ADA2. The overall carrier frequency in the Chinese population was 1.05 % (732/69,413) and the estimated incidence of DADA2 was approximately one in 92,251 individuals. The present study provides an accurate estimation of the prevalence of DADA2 in China, supporting genetic counseling, early diagnosis treatment, and prognostic evaluation.

8.
Foods ; 13(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39272450

RESUMEN

Heavy metal ions such as cadmium, mercury, lead, and arsenic in the soil cannot be degraded naturally and are absorbed by crops, leading to accumulation in agricultural products, which poses a serious threat to human health. Therefore, establishing a rapid and efficient method for detecting heavy metal ions in agricultural products is of great significance to ensuring the health and safety. In this study, a novel optimized spectrometric method was developed for the rapid and specific colorimetric detection of cadmium ions based on N-(2-Acetamido)-iminodiacetic acid (ADA) and Victoria blue B (VBB) as the chromogenic unit. The safety evaluation of ADA showed extremely low biological toxicity in cultured cells and live animals. The standard curve is y = 0.0212x + 0.1723, R2 = 0.9978, and LOD = 0.08 µM (0.018 mg/kg). The liner concentrations detection range of cadmium is 0.1-10 µM. An inexpensive paper strip detection method was developed with a detection limit of 0.2 µM to the naked eye and a detection time of less than 1 min. The method was successfully used to assess the cadmium content of rice, soybean, milk, grape, peach, and cabbage, and the results correlated well with those determined by inductively coupled plasma-mass spectrometry (ICP-MS). Thus, our study demonstrated a novel rapid, safe, and economical method for onsite, real-time detection of cadmium ions in agricultural products.

9.
FEMS Microbiol Ecol ; 100(10)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39227168

RESUMEN

Untargeted genetic approaches can be used to explore the high metabolic versatility of cyanobacteria. In this context, a comprehensive metagenomic shotgun analysis was performed on a population of Dolichospermum lemmermannii collected during a surface bloom in Lake Garda in the summer of 2020. Using a phylogenomic approach, the almost complete metagenome-assembled genome obtained from the analysis allowed to clarify the taxonomic position of the species within the genus Dolichospermum and contributed to frame the taxonomy of this genus within the ADA group (Anabaena/Dolichospermum/Aphanizomenon). In addition to common functional traits represented in the central metabolism of photosynthetic cyanobacteria, the genome annotation uncovered some distinctive and adaptive traits that helped define the factors that promote and maintain bloom-forming heterocytous nitrogen-fixing Nostocales in oligotrophic lakes. In addition, genetic clusters were identified that potentially encode several secondary metabolites that were previously unknown in the populations evolving in the southern Alpine Lake district. These included geosmin, anabaenopetins, and other bioactive compounds. The results expanded the knowledge of the distinctive competitive traits that drive algal blooms and provided guidance for more targeted analyses of cyanobacterial metabolites with implications for human health and water resource use.


Asunto(s)
Lagos , Metagenoma , Metagenómica , Filogenia , Lagos/microbiología , Eutrofización , Cianobacterias/genética , Cianobacterias/clasificación , Cianobacterias/crecimiento & desarrollo , Cianobacterias/metabolismo , Aphanizomenon/genética , Aphanizomenon/crecimiento & desarrollo , Aphanizomenon/metabolismo
10.
Indian J Tuberc ; 71(4): 389-394, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39278671

RESUMEN

BACKGROUND: Tubercular Pleural effusion (TBPE) is one of most common extrapulmonary tuberculosis. It can be difficult to diagnose due to low sensitivity of pleural fluid smear, culture and CBNAAT. Diagnosis of TBPE is then dependent on the level of pleural fluid Adenosine Deaminase (ADA). Thoracoscopic pleural biopsy gives definite diagnosis specially in Low Pleural fluid ADA setting. AIMS AND OBJECTIVE: This study was planned to find out the prevalence of tubercular etiology in patients of exudative pleural effusion with low ADA (ADA <40 IU/L). MATERIAL AND METHODS: A Prospective, observational study was carried out in a tertiary teaching institute in north India. Total 142 patients of pleural effusion with low ADA were enrolled. All patients underwent rigid thoracoscopy for confirmation of their diagnosis. RESULTS: Out of 142 patients, male were 78 (55%) and female were 64 (45%). Mean age of patients were 57.4 years. Tuberculosis was diagnosed as a cause of effusion in 22 (15.5%) out of 142 patients. Majority of TBPE patients had pleural thickening as thoracoscopic finding. Mean ADA level in TBPE was 27.36 ± 11.6 as compared to 18.55 ± 9.02 in non tubercular pleural effusion patients and this difference was significant statistically (P- 0.002). CONCLUSION: The diagnosis of patients having exudative, low ADA pleural effusion can be very easily confirmed by thoracoscopy guided pleural biopsy which has a very high diagnostic yield.


Asunto(s)
Adenosina Desaminasa , Derrame Pleural , Toracoscopía , Tuberculosis Pleural , Humanos , Masculino , Adenosina Desaminasa/análisis , Adenosina Desaminasa/metabolismo , Femenino , Derrame Pleural/diagnóstico , Toracoscopía/métodos , Persona de Mediana Edad , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/patología , Estudios Prospectivos , Adulto , India/epidemiología , Anciano
12.
Cureus ; 16(7): e64505, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39139350

RESUMEN

A 63-year-old man had been smoking bidis for 25 years and developed tubercular empyema, further complicated by pneumothorax and other pulmonary issues. Over a period of three weeks, the individual experienced a gradual onset of symptoms, including progressive shortness of breath, cough, fever, and chest pain. Radiographic examinations revealed significant left-sided pleural effusion with consolidation and evidence of pneumothorax. Other findings included anemia, hyponatremia, substantially increased lactate dehydrogenase, and adenosine deaminase (ADA), consistent with tubercular or chronic infection. The comprehensive treatment plan involved the administration of antibiotics, antitubercular drugs, draining of the pleural fluid, nebulized bronchodilators, corticosteroids, and broad-spectrum antibiotics. The patient exhibited a positive response, showing notable clinical improvement, which was closely monitored through sequential chest X-rays and ECGs. This would continue to highlight the vital need for early tuberculosis detection in patients with chronic obstructive pulmonary disease due to clinical overlap with other diseases. To diagnose and follow up on tuberculous pleural effusion cases, it was critical to integrate both clinical and radiographic findings with laboratory data. It emphasizes the necessity for a multidisciplinary approach to improve overall treatment outcomes.

13.
Front Endocrinol (Lausanne) ; 15: 1416234, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39145313

RESUMEN

Objective: To investigate the factors influencing accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Methods: A total of 216 patients diagnosed with T2DM and CHD between August 2019 and August 2023 at Xuzhou Central Hospital were selected. Patients were divided into an aging group and a non-aging group, based on the positive or negative values of phenotypic age acceleration (PhenoAgeAccel). Logistic regression analysis was conducted. Variables that had a univariate analysis P< 0.05 were included in the multivariate analysis to identify factors influencing aging in patients with T2DM and CHD, and the area under the curve of the model was reported. Results: This study included 216 patients, with 89 in the accelerated aging group, and 127 in the non-accelerated aging group. The average age of patients was 70.40 (95% CI: 69.10-71.69) years, with 137 males (63.4%). Compared with the non-accelerated aging group, patients in the accelerated aging group were older, with a higher proportion of males, and a higher prevalence of hypertension, stable angina pectoris, and unstable angina pectoris. Multivariate Logistic regression analysis indicated that the absolute value of neutrophils (NEUT#), urea (UREA), adenosine deaminase (ADA), and the triglyceride-glucose index (TyG) were risk factors for accelerated aging, while cholinesterase (CHE) was a protective factor. For each unit increase in NEUT#, UREA, ADA, and TyG, the risk of aging increased by 64%, 48%, 10%, and 789%, respectively. The overall area under the receiver operating characteristic (ROC) curve of the model in the training set was 0.894, with a 95% confidence interval (CI) of 0.851-0.938. Conclusion: NEUT#, CHE, UREA, ADA, and TyG are predictors of accelerated aging in patients with T2DM and CHD, with the model showing favorable overall predictive performance.


Asunto(s)
Enfermedad Coronaria , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Anciano , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/sangre , Persona de Mediana Edad , Envejecimiento Prematuro/epidemiología , Factores de Riesgo , Envejecimiento , Triglicéridos/sangre , China/epidemiología , Adenosina Desaminasa/metabolismo , Urea/sangre
14.
ACS Appl Mater Interfaces ; 16(34): 44605-44622, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39159061

RESUMEN

Skeletal muscle tissue can be severely damaged by disease or trauma beyond its ability to self-repair, necessitating the further development of biofabrication and tissue-engineering tools for reconstructive processes. Hence, in this study, a composite bioink of oxidized alginate (ADA) and gelatin (GEL) including cell-laden ribbon-shaped fillers is used for enhancing cell alignment and the formation of an anisotropic structure. Different plasma treatments combined with protein coatings were evaluated for the improvement of cell adhesion to poly(lactic-co-glycolic acid) (PLGA) ribbon surfaces. Oxygen plasma activation of 30 W for 5 min showed high immobilization of fibronectin as a protein coating on the PLGA ribbon surface, which resulted in enhanced cell adhesion and differentiation of muscle cells. Furthermore, the effect of various concentrations of CaCl2 solution, used for ionic cross-linking of ADA, on ADA-GEL physical and mechanical properties as well as encapsulated C2C12 cell viability and proliferation behavior was investigated. The pore area was measured via two approaches, cryofixation and lyophilization, which, in accordance with degradation tests and mechanical analysis, showed that 60 mM CaCl2 concentration is the optimum range for cross-linking of the formulation of ADA 2.5%w/v-GEL 3.75%w/v. These cross-linked hydrogels showed a compression modulus of 11.5 kPa (similar to the native skeletal muscle tissue), a high viability of C2C12 muscle cells (>80%), and a high proliferation rate during 7 days of culture. Rheological characterization of the ADA-GEL composite hydrogel containing short fillers (100 µm long) showed its suitability as a bioink with shear-thinning and flow behavior compared to ADA-GEL.


Asunto(s)
Alginatos , Gelatina , Hidrogeles , Músculo Esquelético , Ingeniería de Tejidos , Gelatina/química , Alginatos/química , Animales , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/citología , Línea Celular , Andamios del Tejido/química , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Diferenciación Celular/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología
15.
Turk J Haematol ; 41(3): 133-140, 2024 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-39120005

RESUMEN

Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessively inherited autoinflammatory disorder caused by loss-of-function mutations in the ADA2 gene. Although the pathogenesis involves the triggering of a proinflammatory cascade due to increased production of inflammatory cytokines such as tumor necrosis factor (TNF)-α and dysregulation of neutrophil extracellular trap formation resulting from an excess accumulation of extracellular adenosine, the pathogenetic mechanism still needs further clarification due to the broad clinical spectrum. In addition to the initially described vasculitis-related symptoms, hematological, immunological, and autoinflammatory symptoms are now well recognized. The diagnosis is made by demonstration of pathogenic variants of ADA2 with biallelic loss of function and identification of low plasma ADA2 catalytic activity. Currently, TNF-α inhibitors are the treatment of choice for controlling vasculitis manifestations and preventing strokes. However, in patients presenting with severe hematologic findings, TNF-α inhibitors are not the treatment of choice and hematopoietic stem cell transplantation has been shown to be successful in selected cases. Recombinant ADA2 protein and gene therapy are promising treatment modalities for the future. In conclusion, ADA2 deficiency has a broad phenotype and should be considered in the differential diagnosis of different clinical situations. In this review, we summarize the disease manifestations of ADA2 deficiency and available treatment options.


Asunto(s)
Adenosina Desaminasa , Humanos , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Péptidos y Proteínas de Señalización Intercelular/genética , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/terapia , Agammaglobulinemia/genética , Trasplante de Células Madre Hematopoyéticas , Fenotipo , Terapia Genética/métodos , Manejo de la Enfermedad , Factor de Necrosis Tumoral alfa , Mutación , Inmunodeficiencia Combinada Grave , Enfermedades Autoinflamatorias Hereditarias
16.
Genes Dev ; 38(15-16): 738-754, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39168636

RESUMEN

Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation. Analyses of data sets in the Cancer Dependency Map Project revealed that many SAGA components are selective dependencies in MM. To define SAGA-specific functions, we focused on ADA2B, the only subunit in the lysine acetyltransferase (KAT) module that specifically functions in SAGA. Integration of RNA sequencing (RNA-seq), assay for transposase-accessible chromatin with sequencing (ATAC-seq), and cleavage under targets and release using nuclease assay (CUT&RUN) results identified pathways directly regulated by ADA2B including MTORC1 signaling and oncogenic programs driven by MYC, E2F, and MM-specific MAF. We discovered that ADA2B is recruited to MAF and MYC gene targets, and that MAF shares a majority of its targets with MYC in MM cells. Furthermore, we found that the SANT domain of ADA2B is required for interaction with both GCN5 and PCAF acetyltransferases, incorporation into SAGA, and ADA2B protein stability. Our findings uncover previously unknown SAGA KAT module-dependent mechanisms controlling MM cell growth, revealing a vulnerability that might be exploited for future development of MM therapy.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Mieloma Múltiple , Mieloma Múltiple/genética , Humanos , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-maf/genética , Proteínas Proto-Oncogénicas c-maf/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Transducción de Señal/genética
17.
Genes Dev ; 38(15-16): 693-694, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39168637

RESUMEN

The SAGA complex is an evolutionarily conserved histone acetyltransferase complex and transcription coactivator essential for development and disease. Dysregulation of SAGA is implicated in various human diseases, including cancer. In this issue of Genes & Development, Chen et al. (doi:10.1101/gad.351789.124) uncover a critical role for SAGA in multiple myeloma wherein SAGA's ADA2B component is required for the expression of mTORC1 pathway genes and targets of the MYC, E2F, and MAF (musculoaponeurotic fibrosarcoma) transcription factors. SAGA cooperates with MYC and MAF to sustain oncogenic gene expression programs vital for multiple myeloma survival and thus may serve as a therapeutic target for future cancer therapies.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Mieloma Múltiple , Proteínas Proto-Oncogénicas c-maf , Proteínas Proto-Oncogénicas c-myc , Mieloma Múltiple/genética , Humanos , Proteínas Proto-Oncogénicas c-maf/genética , Proteínas Proto-Oncogénicas c-maf/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transactivadores/genética , Transactivadores/metabolismo , Animales
18.
Cureus ; 16(7): e65659, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39205740

RESUMEN

Introduction Pleural effusion is a challenging diagnosis at times, especially due to the overlap of symptoms in effusions of various etiologies. In this study, we aimed to identify if pleural fluid adenosine deaminase (ADA) or serum C-reactive protein (CRP) can be used as an additional novel biomarker for ADA in diagnosing tubercular, parapneumonic, and malignant pleural effusions. Materials and methods A prospective, observational, cross-sectional study was conducted on 79 patients diagnosed with tubercular, parapneumonic, or malignant pleural effusion from August 2022 to April 2024 at the Department of Respiratory Medicine at Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pimpri, Pune. The pleural fluid ADA/serum CRP ratio was identified in each group, and analysis was done to compare the ratio in each group. The correlation with pleural fluid ADA was also identified. Results A total of 79 patients were enrolled in this study. Out of these patients, 53 (67.1%) were identified as having tubercular pleural effusion, 10 (12.7%) patients had parapneumonic effusion, and 16 (20.3%) had malignant pleural effusion. For malignant effusions, the area under the curve (AUC) using the receiver operating characteristic (ROC) for the ADA/CRP ratio was observed to be 0.862. Sensitivity was 87.50% and specificity was 82.54% at a cut-off value of ≤0.5. The positive predictive value was found to be 56%, and the negative predictive value was found to be 96.3%. For parapneumonic effusions, the AUC using the ROC for the ADA/CRP ratio was observed to be 0.880. Sensitivity was 100% and specificity was 69.57% at a cut-off value of ≤0.67. The positive predictive value was found to be 32.3%, and the negative predictive value was found to be 100%. For tubercular effusions, the AUC using the ROC for the ADA/CRP ratio was observed to be 0.955. Sensitivity was 92.45% and specificity was 88.46% at a cut-off value of >0.54. The positive predictive value was found to be 94.2%, and the negative predictive value was found to be 85.2%. The Pearson correlation coefficient (r) of 0.633 indicates a moderately strong positive linear relationship between ADA and ADA/CRP levels. Conclusion The pleural fluid ADA-to-serum CRP ratio can be used as a useful diagnostic tool for differentiating between tubercular, parapneumonic, and malignant pleural effusions. ADA/CRP ratio has added diagnostic value over ADA. In clinically puzzling scenarios, the ADA/CRP ratio can be a cost-effective tool before opting for a more expensive and invasive procedure, which is also often difficult to obtain in resource-limited healthcare settings. More research with a larger sample size is indicated to incorporate the ADA/CRP ratio as an added diagnostic tool along with ADA.

19.
J Immunol Methods ; 532: 113717, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38960066

RESUMEN

Monitoring belimumab concentrations in patients can be a valuable tool for assessing treatment response and for personalizing drug doses. Various assay formats may be used to measure concentrations of therapeutic monoclonal antibodies. A particularly useful format involves the use of anti-idiotype monoclonal antibodies, selected to be highly specific to the antibody of interest. Here, we describe the development of a specific, high-affinity anti-idiotype antibody to belimumab, and the application of this antibody in a homologous sandwich ELISA to measure belimumab concentrations.


Asunto(s)
Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Monitoreo de Drogas , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/inmunología , Humanos , Ensayo de Inmunoadsorción Enzimática/métodos , Monitoreo de Drogas/métodos , Anticuerpos Antiidiotipos/inmunología , Animales , Inmunosupresores/sangre
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