Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 270
Filtrar
1.
Immunol Lett ; 270: 106913, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233252

RESUMEN

OBJECTIVE: This study seeks to elucidate the expression, function, and clinical relevance of the T cell receptor interacting molecule (TRIM) within circulating CD4+T cell subsets in systemic lupus erythematosus (SLE) patients. METHODS: We assessed TRIM expression across distinct subpopulations of human peripheral blood mononuclear cells (PBMCs) through the analysis of publicly available single-cell RNA sequencing data. In addition, TRIM expression was investigated within CD4+T cell subsets of peripheral blood and spleens in mice. PBMCs were isolated from both SLE patients, healthy controls (HCs) and rheumatoid arthritis (RA) patients with subsequent measurement and comparative analysis of TRIM expression and functional molecules using flow cytometry. To gauge the clinical relevance of TRIM in SLE, correlation and ROC curve analyses were performed. RESULTS: In both healthy humans and mice, TRIM was higher expressed within CD4+T cell subsets, especially in naive CD4+T cells. TRIM+ Tregs exhibited lower Helios+ cells and CD45RA-FoxP3hi cells percentages compared to TRIM- Treg cells. TRIM+T cells demonstrated reduced granzyme B and perforin secretion and increased IFN-γ secretion in comparison to TRIM- T cells. Notably, the proportion of TRIM+CD4+T cells was diminished in SLE patients. The downregulation of TRIM+ in CD4+T cells positively correlated with diminished complement C3 and C1q levels and inversely correlated with CRP. The identification of TRIM-associated CD4 T cell subsets aids in distinguishing SLE patients from HCs and those with RA. CONCLUSIONS: Reduced TRIM expression is linked to abnormal CD4+T cell activation in SLE. TRIM-associated CD4+T cells may be implicated in the pathogenesis of SLE and hold potential for clinical diagnostic purposes.

2.
Am J Transl Res ; 16(8): 3472-3479, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39262705

RESUMEN

Glial fibrillary acidic protein (GFAP) is a marker associated with astrocyte activation and plays a role in various pathologic processes, including traumatic brain injury, stroke, and neurodegenerative diseases. Interacting boson approximation (Iba-1) is a marker protein for microglia, which are important in neuroinflammatory responses. This meta-analysis aimed to investigate the impact of general anesthetics on the expression of GFAP and Iba-1 in animal models. A meta-analysis was conducted using databases such as PubMed, EMBASE, Springer, and Web of Science. The quality of the selected publications was estimated using the SYRCLE guidelines to ensure credibility and consistency of the research. Continuous variables were measured using mean difference or standardized mean difference (SMD), with a 95% confidence interval (CI) calculated. Ten randomized controlled animal experiments were included in this analysis, utilizing different general anesthetics such as sevoflurane and propofol compared to untreated control groups. The results consistently demonstrated a significant increase in GFAP (SMD = 0.41, 95% CI: 0.09, 0.72, P = 0.01) and Iba-1 (SMD = 0.43, 95% CI: 0.04, 0.83, P = 0.03) expression in the general anesthetic-treated groups, suggesting a neuroinflammatory response induced by these agents. Assessment of publication bias revealed no significant bias in the included studies. This meta-analysis highlights the impact of general anesthetics on GFAP expression in animal models, emphasizing the importance of understanding the neuroinflammatory response associated with anesthesia administration. Further research is warranted to elucidate the underlying molecular pathways and explore possible therapeutic interventions to mitigate adverse effects associated with anesthesia administration.

3.
Sci Rep ; 14(1): 19425, 2024 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169054

RESUMEN

This paper introduces the efficient medical-images-aimed segment anything model (EMedSAM), addressing the high computational demands and limited adaptability of using SAM for medical image segmentation tasks. We present a novel, compact image encoder, DD-TinyViT, designed to enhance segmentation efficiency through an innovative parameter tuning method called med-adapter. The lightweight DD-TinyViT encoder is derived from the well-known ViT-H using a decoupled distillation approach.The segmentation and recognition capabilities of EMedSAM for specific structures are improved by med-adapter, which dynamically adjusts the model parameters specifically for medical imaging. We conducted extensive testing on EMedSAM using the public FLARE 2022 dataset and datasets from the First Hospital of Zhejiang University School of Medicine. The results demonstrate that our model outperforms existing state-of-the-art models in both multi-organ and lung segmentation tasks.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Pulmón/diagnóstico por imagen , Diagnóstico por Imagen/métodos , Tomografía Computarizada por Rayos X/métodos , Modelos Teóricos
4.
J Forensic Sci ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169518

RESUMEN

Next-generation sequencing (NGS) technologies have expanded the spectrum of forensic DNA analysis by facilitating efficient and precise genotyping of a large number of genetic markers. Yet, challenges persist regarding complex sample processing and assurance of equal molar concentrations across pooled samples. Since optimal cluster density is crucial for sequencing performance, the determination of both quantity and quality is indispensable for library preparation. In this study, we investigated the application of the Agilent 2100 Bioanalyzer for library quality control, as studies for forensic approaches, particularly for highly degraded postmortem samples, are rare. Our analysis encompassed assessing total DNA concentrations, fluorescence unit (FU) values, and adapter dimer concentrations in purified DNA libraries derived from buccal swabs and tissue samples of decomposed corpses. The sensitivity study tested a serial dilution derived from buccal swabs and revealed a decrease in FU values and an increase in adapter dimers with declining DNA input concentrations. Deviations in total DNA concentrations and average peak heights between the Agilent 2100 Bioanalyzer runs indicated a lack of repeatability in data and presented challenges in accurate quantification, which was also observed in previous studies. Yet, the analysis of degraded samples from decomposed human remains has shown the ability to detect adapter dimer concentrations, which can be crucial for the quality of subsequent NGS library preparation and sequencing success. Therefore, the Agilent 2100 Bioanalyzer proves to be a valuable tool for NGS quality control.

5.
J Thorac Dis ; 16(7): 4607-4618, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39144353

RESUMEN

Background: Andrographolide sulfonate (Andro-S), a traditional Chinese medicine, is commonly used to treat pediatric respiratory tract infections in China. However, its therapeutic effects in infections caused by respiratory syncytial virus (RSV) have not been reported. We thus aimed to investigate the therapeutic effects of Andro-S using a mouse model of RSV infection-induced airway inflammation. Methods: Immunocompromised (cyclophosphamide-treated) BALB/c mice were intranasally infected with RSV and treated with intranasal or intraperitoneal Andro-S once daily for five consecutive days, starting on the day of infection. Histopathological changes in the lung were evaluated using hematoxylin and eosin staining. Total inflammatory cell counts and macrophage, lymphocyte, neutrophil, and eosinophil counts in the bronchoalveolar lavage fluid (BALF) were microscopically determined. Interferon-γ (IFN-γ) levels in the BALF were detected using enzyme-linked immunosorbent assay (ELISA). The messenger RNA levels of RSV nucleoprotein (N) and Toll-like receptors (TLRs) 1-9 in lung tissues were determined with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of RSV N, RSV fusion protein (F), TLR2, TLR3, and TIR domain-containing adapter-inducing interferon-ß (TRIF) were detected via Western blot analysis. Results: RSV infection caused lung inflammation, manifesting as bronchiolitis, alveolitis, and perivascular inflammation; increased the number of inflammatory cells; and elevated IFN-γ levels in the BALF. Lung inflammation was positively correlated with pulmonary RSV N levels in infected mice. Intranasal Andro-S significantly downregulated RSV N, RSV F, TLR3, and TRIF protein expression in the lung and ameliorated lung inflammation in infected animals. However, intraperitoneal Andro-S showed no effects on lung inflammation caused by RSV infection. Conclusions: Intranasal Andro-S inhibits RSV replication and ameliorates RSV infection-induced lung inflammation by downregulating TLR3 and TRIF. Therefore, intranasal administration may be a suitable drug delivery method for treating RSV infection.

6.
Stem Cell Res Ther ; 15(1): 258, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39135132

RESUMEN

BACKGROUND: Alzheimer disease (AD) is a heterogenous and multifactorial disease, and its pathology is partly driven by microglia and their activated phenotype. Brain organoids (BOs) are gaining prominence as a relevant model of the human brain for the study of AD; however, BOs are commonly devoid of microglia. To overcome this limitation, current protocols incorporate microglia through either (1) co-culture (BO co-culture), or (2) molecular manipulation at critical windows of BO development to have microglia arise innately (BO innate cultures). It is currently unclear whether the microglia incorporated into BOs by either of these two protocols differ in function. METHODS: At in vitro day 90, BO innate cultures and BO-co-cultures were challenged with the AD-related ß-amyloid peptide (Aß) for up to 72 h. After Aß challenge, BOs were collected for immunoblotting. Immunoblots compared immunodensity and protein banding of Aß and ionized calcium-binding adapter molecule 1 (IBA1, a marker of microglial activation) in BOs. The translational potential of these observations was supported using 56 human cortical samples from neurocognitively normal donors and patients with early-onset AD and late-onset AD. Statistical analyses were conducted using the Kruskal-Wallis test, a two-way ANOVA, or a simple linear regression, and where applicable, followed by Dunn's or Sidak's test. RESULTS: We show that BO co-cultures promote Aß oligomerization as early as 24 h and this coincides with a significant increase in IBA1 levels. In contrast, the Aßs do not oligomerize in BO innate cultures and the IBA1 response was modest and only emerged after 48 h. In human cortical samples, we found IBA1 levels correlated with age at onset, age at death, and the putative diagnostic Aß(1-42)/Aß(1-40) ratio (particularly in their oligomeric forms) in a sex-dependent manner. CONCLUSIONS: Our unique observations suggest that BOs with innate microglia model the response of a healthy brain to Aß, and by extension the initial stages of Aß challenge. It would be impossible to model these early stages of pathogenesis in BOs where microglia are already compromised, such as those with microglia incorporated by co-culture.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Encéfalo , Técnicas de Cocultivo , Microglía , Organoides , Humanos , Microglía/metabolismo , Técnicas de Cocultivo/métodos , Péptidos beta-Amiloides/metabolismo , Organoides/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Femenino , Masculino , Anciano , Persona de Mediana Edad
7.
J Arthroplasty ; 39(10): 2561-2568, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39025279

RESUMEN

BACKGROUND: Outcomes and safety of "mix and match" in total hip arthroplasty (THA) using universal head-neck adapters (UHNA) are a matter of ongoing discussion and concern due to legal affairs. This study aimed at analyzing the "mix and match" use of UHNA and evaluating complication and reoperation rates, possible risk factors, and the implant's survival. METHODS: A total of 306 patients treated with THA (94.1% revisions) using a UHNA at our institution between 2006 and 2022 were identified and included. Diagnoses, comorbidities, implants, and UHNA specifications were retrospectively recorded. Outcomes, complications, and survival analyses were evaluated, taking into account various possible risk factors. RESULTS: There were 19.9% of the 306 included cases (58.5% women; median age 74 years; median follow-up 57 months) that had at least 1 complication. There were 43 patients (14.1%) who had to receive ≥1 rerevision surgery. The most common complication was postoperative recurrent dislocation (n = 27, 8.8%). There was one case of a prosthetic stem-neck fracture that was registered. Statistically significant risk factors for postoperative recurrent dislocations and postoperative aseptic loosening were, respectively, dislocation as an indication for UHNA implantation (P < .001) and oversized neck lengths (≥2XL; P = .004). The overall revision-free survival was 92% after 1 year and 82% at ten years. Statistically significant better survival rates were registered in patients ≥60 years old, who had fewer comorbidities (<2), and normal neck lengths (S to XL). CONCLUSIONS: The results of this study underline the overall safety of UHNA use in THA through "mix and match." Only one case of a stem-neck fracture was identified. The highlighted risk factors for failure must be kept in mind during the decision-making process with patients.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Falla de Prótesis , Reoperación , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/instrumentación , Femenino , Masculino , Anciano , Reoperación/estadística & datos numéricos , Prótesis de Cadera/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , Factores de Riesgo , Diseño de Prótesis , Adulto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
8.
Genet Test Mol Biomarkers ; 28(7): 267-274, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39034913

RESUMEN

Background: A high-altitude environment has inhibitory effects on obesity. Tibetans are not a high-risk population for obesity, but there are still obese individuals within that population. Obesity has become a worldwide health problem, and previous studies have found that obesity is closely associated with hereditary factors. Few studies have investigated obesity in Tibetans, and the association between gene polymorphisms and obesity in Tibetans remains unclear. Methods: Our study investigated the fat mass of 140 native Tibetan individuals (70 men and 70 women) from Lhasa and analyzed the associations between polymorphisms of melanocortin 4 receptor (MC4R), Src homology 2B adapter protein 1 (SH2B1), and neuronal growth regulator 1 (NEGR1) and obesity. Result: Among Tibetan individuals, there were differences in genotype and allele frequencies between those in the obesity group and those in the healthy group at MC4R (rs17782313) and SH2B1 (rs7359397). The polymorphisms of MC4R (rs17782313) were associated with fat mass and obesity in Tibetan men and women, and there was an association between SH2B1 (rs7359397) polymorphisms and fat mass and obesity in Tibetan men. However, polymorphisms of NEGR1 (rs3101336) were not associated with fat mass or obesity in Tibetan individuals. Conclusion: Among Tibetan individuals, polymorphisms of MC4R (rs17782313) and SH2B1 (rs7359397) were associated with obesity, but NEGR1 (rs3101336) polymorphisms were not associated with obesity.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Moléculas de Adhesión Celular Neuronal , Obesidad , Receptor de Melanocortina Tipo 4 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Adaptadoras Transductoras de Señales/genética , Alelos , Estudios de Casos y Controles , Moléculas de Adhesión Celular Neuronal/genética , Pueblos del Este de Asia/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Proteínas Ligadas a GPI , Obesidad/genética , Polimorfismo de Nucleótido Simple , Receptor de Melanocortina Tipo 4/genética , Tibet
9.
3D Print Med ; 10(1): 23, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028380

RESUMEN

BACKGROUND: The revolutionary technology of smartphone-based retinal imaging has been consistently improving over the years. Smartphone-based retinal image acquisition devices are designed to be portable, easy to use, and cost-efficient, which enables eye care to be more widely accessible especially in geographically remote areas. This enables early disease detection for those who are in low- and middle- income population or just in general has very limited access to eye care. This study investigates the limitation of smartphone compatibility of existing smartphone-based retinal image acquisition devices. Additionally, this study aims to propose a universal adapter design that is usable with an existing smartphone-based retinal image acquisition device known as the PanOptic ophthalmoscope. This study also aims to simulate the reliability, validity, and performance overall of the developed prototype. METHODS: A literature review has been conducted that identifies the limitation of smartphone compatibility among existing smartphone-based retinal image acquisition devices. Designing and modeling of proposed adapter were performed using the software AutoCAD 3D. For the proposed performance evaluation, finite element analysis (FEA) in the software Autodesk Inventor and 5-point scale method were demonstrated. RESULTS: Published studies demonstrate that most of the existing smartphone-based retinal imaging devices have compatibility limited to specific older smartphone models. This highlights the benefit of a universal adapter in broadening the usability of existing smartphone-based retinal image acquisition devices. A functional universal adapter design has been developed that demonstrates its compatibility with a variety of smartphones regardless of the smartphone dimension or the position of the smartphone's camera lens. The proposed performance evaluation method generates an efficient stress analysis of the proposed adapter design. The end-user survey results show a positive overall performance of the developed universal adapter. However, a significant difference between the expert's views on the developed adapter and the quality of images is observed. CONCLUSION: The compatibility of existing smartphone-based retinal imaging devices is still mostly limited to specific smartphone models. Besides this, the concept of a universal and suitable adapter for retinal imaging using the PanOptic ophthalmoscope was presented and validated in this paper. This work provides a platform for future development of smartphone-based ophthalmoscope that is universal.

10.
Artif Intell Med ; 154: 102926, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38964193

RESUMEN

Pathological myopia (PM) is the leading ocular disease for impaired vision worldwide. Clinically, the characteristics of pathology distribution in PM are global-local on the fundus image, which plays a significant role in assisting clinicians in diagnosing PM. However, most existing deep neural networks focused on designing complex architectures but rarely explored the pathology distribution prior of PM. To tackle this issue, we propose an efficient pyramid channel attention (EPCA) module, which fully leverages the potential of the clinical pathology prior of PM with pyramid pooling and multi-scale context fusion. Then, we construct EPCA-Net for automatic PM recognition based on fundus images by stacking a sequence of EPCA modules. Moreover, motivated by the recent pretraining-and-finetuning paradigm, we attempt to adapt pre-trained natural image models for PM recognition by freezing them and treating the EPCA and other attention modules as adapters. In addition, we construct a PM recognition benchmark termed PM-fundus by collecting fundus images of PM from publicly available datasets. The comprehensive experiments demonstrate the superiority of EPCA-Net over state-of-the-art methods in the PM recognition task. For example, EPCA-Net achieves 97.56% accuracy and outperforms ViT by 2.85% accuracy on the PM-fundus dataset. The results also show that our method based on the pretraining-and-finetuning paradigm achieves competitive performance through comparisons to part of previous methods based on traditional fine-tuning paradigm with fewer tunable parameters, which has the potential to leverage more natural image foundation models to address the PM recognition task in limited medical data regime.


Asunto(s)
Redes Neurales de la Computación , Humanos , Miopía Degenerativa , Aprendizaje Profundo , Fondo de Ojo , Interpretación de Imagen Asistida por Computador/métodos
11.
Stud Health Technol Inform ; 315: 659-660, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049369

RESUMEN

This study introduces the "Adjustable Oxygen Adapter," designed to address interruptions in oxygen supply for patients transitioning from oxygen spray bottles, particularly in wards with single-outlet flowmeters. Inspired by the "Three-Way Piston Rotating Adapter," this innovative design, operated by a single switch, ensures uninterrupted oxygen supply during equipment changes. Stability testing, conducted with a flow monitor by a respiratory therapist, confirms that the adapter provides a stable flow rate and oxygen concentration, offering a practical solution for seamless transitions between oxygen devices in clinical settings.


Asunto(s)
Diseño de Equipo , Terapia por Inhalación de Oxígeno , Seguridad del Paciente , Humanos , Terapia por Inhalación de Oxígeno/instrumentación , Terapia por Inhalación de Oxígeno/métodos , Oxígeno/administración & dosificación
12.
Front Psychol ; 15: 1429232, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035091

RESUMEN

Previous research has argued that consecutive interpreters constitute laminated speakers in the sense that they engage with different kinds of footing at once, representing another's point of view through their words in another language. These multiple roles also play out in their gesturing, as they sometimes indicate deictically who is the source of the ideas and stances they are expressing (the principal). Simultaneous interpreters, though, often work in an interpreting booth; they are often not seen by the audience, yet many of them gesture, sometimes frequently. How are simultaneous interpreters using gesture in relation to stance-taking and footing? We consider the case of simultaneous interpreters rendering popular science lectures between (both to and from) Russian (their L1) and either English or German (their L2). Though only hearing the audio of the lectures, the interpreters produced many gestures, which were analyzed for their function. Some representational and deictic gestures appeared to clearly involve the interpreter as the principal (writing numbers with one's finger to help remember them or pointing to two places on the desk to keep track of two different quantities mentioned). Other representational and deictic gestures are ambiguous as to whether they are enacting what the interpreter may have imagined what the lecturer did or whether they arose out of the interpreter's own thinking for speaking (e.g., tracing the form of a bird being mentioned or pointing to an empty space when the lecturer was referring to a graph). Pragmatic gestures, showing one's stance toward the topic of the talk, were the most ambiguous as to the footing, reflecting how the interpreter may be engaged in fictive interaction with their imagined audience. Self-adapters, however, more clearly involve the interpreter as the principal, as such actions are known to support cognitive focussing and self-soothing. In sum, we see varying degrees of clarity as to whose stance and principal footing simultaneous interpreters are expressing bodily as laminated speakers. The variable ambiguity can be attributed to the nature of gesture as a semiotic system, the functions of which are more often dependent on co-occurring speech than vice versa.

13.
Neural Netw ; 178: 106414, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38936110

RESUMEN

The recent surge in large-scale foundation models has spurred the development of efficient methods for adapting these models to various downstream tasks. Low-rank adaptation methods, such as LoRA, have gained significant attention due to their outstanding parameter efficiency and no additional inference latency. This paper investigates a more general form of adapter module based on the analysis that parallel and sequential adaptation branches learn novel and general features during fine-tuning, respectively. The proposed method, named Hydra, combines parallel and sequential branch to integrate capabilities, which is more expressive than existing single branch methods and enables the exploration of a broader range of optimal points in the fine-tuning process. In addition, the proposed method explicitly leverages the pre-trained weights by performing a linear combination of the pre-trained features. It allows the learned features to have better generalization performance across diverse downstream tasks. Furthermore, we perform a comprehensive analysis of the characteristics of each adaptation branch with empirical evidence. Through an extensive range of experiments, we substantiate the efficiency and demonstrate the superior performance of Hydra. This comprehensive evaluation underscores the potential impact and effectiveness of Hydra in a variety of applications. The source code of this work is publicly opened on https://github.com/extremebird/Hydra.


Asunto(s)
Redes Neurales de la Computación , Algoritmos
14.
Reprod Sci ; 31(8): 2199-2208, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38907125

RESUMEN

Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A165) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A165 (1 × 1010 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR.


Asunto(s)
Adenoviridae , Encéfalo , Retardo del Crecimiento Fetal , Terapia Genética , Microglía , Arteria Uterina , Factor A de Crecimiento Endotelial Vascular , Animales , Cobayas , Embarazo , Femenino , Terapia Genética/métodos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Retardo del Crecimiento Fetal/terapia , Retardo del Crecimiento Fetal/metabolismo , Adenoviridae/genética , Encéfalo/metabolismo , Encéfalo/patología , Microglía/metabolismo , Desarrollo Fetal/fisiología , Vectores Genéticos
15.
Int J Biol Sci ; 20(8): 2881-2903, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904019

RESUMEN

The mechanism that maintains ER-to-Golgi vesicles formation and transport is complicated. As one of the adapters, Ninein-like protein (Nlp) participated in assembly and transporting of partial ER-to-Golgi vesicles that contained specific proteins, such as ß-Catenin and STING. Nlp acted as a platform to sustain the specificity and continuity of cargoes during COPII and COPI-coated vesicle transition and transportation through binding directly with SEC31A as well as Rab1B. Thus, we proposed an integrated transport model that particular adapter participated in specific cargo selection or transportation through cooperating with different membrane associated proteins to ensure the continuity of cargo trafficking. Deficiency of Nlp led to vesicle budding failure and accumulation of unprocessed proteins in ER, which further caused ER stress as well as Golgi fragmentation, and PERK-eIF2α pathway of UPR was activated to reduce the synthesis of universal proteins. In contrast, upregulation of Nlp resulted in Golgi fragmentation, which enhanced the cargo transport efficiency between ER and Golgi. Moreover, Nlp deficient mice were prone to spontaneous B cell lymphoma, since the developments and functions of lymphocytes significantly depended on secretory proteins through ER-to-Golgi vesicle trafficking, including IL-13, IL-17 and IL-21. Thus, perturbations of Nlp altered ER-to-Golgi communication and cellular homeostasis, and might contribute to the pathogenesis of B cell lymphoma.


Asunto(s)
Retículo Endoplásmico , Aparato de Golgi , Animales , Humanos , Ratones , Vesículas Cubiertas por Proteínas de Revestimiento/metabolismo , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Transporte de Proteínas
16.
Front Immunol ; 15: 1407992, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887285

RESUMEN

Although adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells has achieved unprecedented response rates in patients with certain hematological malignancies, this therapeutic modality is still far from fulfilling its remarkable potential, especially in the context of solid cancers. Antigen escape variants, off-tumor destruction of healthy tissues expressing tumor-associated antigens (TAAs), poor CAR-T cell persistence, and the occurrence of functional exhaustion represent some of the most prominent hurdles that limit CAR-T cell ability to induce long-lasting remissions with a tolerable adverse effect profile. In this review, we summarize the main approaches that have been developed to face such bottlenecks, including the adapter CAR (AdCAR) system, Boolean-logic gating, epitope editing, the modulation of cell-intrinsic signaling pathways, and the incorporation of safety switches to precisely control CAR-T cell activation. We also discuss the most pressing issues pertaining to the selection of co-stimulatory domains, with a focus on strategies aimed at promoting CAR-T cell persistence and optimal antitumor functionality.


Asunto(s)
Antígenos de Neoplasias , Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Neoplasias/terapia , Neoplasias/inmunología , Antígenos de Neoplasias/inmunología , Animales , Linfocitos T/inmunología , Linfocitos T/trasplante , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/genética
17.
J Control Release ; 372: 648-660, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38936743

RESUMEN

In vitro-In vivo correlation (IVIVC) is a main focus of the pharmaceutical industry, academia and the regulatory sectors, as this is an effective modelling tool to predict drug product in vivo performance based on in vitro release data and serve as a surrogate for bioequivalence studies, significantly reducing the need for clinical studies. Till now, IVIVCs have not been successfully developed for in situ forming implants due to the significantly different in vitro and in vivo drug release profiles that are typically achieved for these dosage forms. This is not unexpected considering the unique complexity of the drug release mechanisms of these products. Using risperidone in situ forming implants as a model, the current work focuses on: 1) identification of critical attributes of in vitro release testing methods that may contribute to differences in in vitro and in vivo drug release from in situ forming implants; and 2) optimization of the in vitro release method, with the aim of developing Level A IVIVCs for risperidone implants. Dissolution methods based on a novel Teflon shape controlling adapter along with a water non-dissolvable glass fiber membrane (GF/F) instead of a water dissolvable PVA film (named as GF/F-Teflon adapter and PVA-Teflon adapter, respectively), and an in-house fabricated Glass slide adapter were used to investigate the impact of: the surface-to-volume ratio, water uptake ratio, phase separation rate (measured by NMP release in 24 h post injection in vitro or in vivo), and mechanical pressure on the drug release patterns. The surface-to-volume ratio and water uptake were shown to be more critical in vitro release testing method attributes compared to the phase separation rate and mechanical pressure. The Glass slide adapter-based dissolution method, which allowed for the formation of depots with bio-mimicking surface-to-volume ratios and sufficient water uptake, has the ability to generate bio-relevant degradation profiles as well as in vitro release profiles for risperidone implants. For the first time, a Level A IVIVC (rabbit model) has been successfully developed for in situ forming implants. Release data for implant formulations with slightly different PLGA molecular weights (MWs) were used to develop the IVIVC. The predictability of the model passed external validation using the reference listed drug (RLD), Perseris®. IVIVC could not be developed when formulations with different PLGA molar ratios of lactic acid to glycolic acid (L/G) were included. The present work provides a comprehensive understanding of the impact of the testing method attributes on drug release from in situ forming implants, which is a valuable practice for level A IVIVC development.


Asunto(s)
Implantes de Medicamentos , Liberación de Fármacos , Risperidona , Risperidona/administración & dosificación , Risperidona/farmacocinética , Risperidona/química , Antipsicóticos/administración & dosificación , Antipsicóticos/farmacocinética , Antipsicóticos/química , Animales , Solubilidad
18.
Genetics ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861412

RESUMEN

Shc proteins function in many different signaling pathways where they mediate phosphorylation-dependent protein-protein interactions. These proteins are characterized by the presence of two phosphotyrosine-binding domains, an N-terminal PTB and a C-terminal SH2. We describe a previously unrecognized C. elegans Shc gene, shc-3 and characterize its role in stress response. Both shc-3 and shc-1 are required for long-term survival in L1 arrest and survival in heat stress, however, they do not act redundantly but rather play distinct roles in these processes. Loss of shc-3 did not further decrease survival of daf-16 mutants in L1 arrest, suggesting that like SHC-1, SHC-3 functions in the Insulin-like signaling pathway. In the absence of SHC-3, DAF-16 nuclear entry and exit are slowed, suggesting that SHC-3 is required for rapid changes in DAF-16 signaling.

19.
Int J Comput Assist Radiol Surg ; 19(7): 1313-1320, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38717737

RESUMEN

PURPOSE: In surgical image segmentation, a major challenge is the extensive time and resources required to gather large-scale annotated datasets. Given the scarcity of annotated data in this field, our work aims to develop a model that achieves competitive performance with training on limited datasets, while also enhancing model robustness in various surgical scenarios. METHODS: We propose a method that harnesses the strengths of pre-trained Vision Transformers (ViTs) and data efficiency of convolutional neural networks (CNNs). Specifically, we demonstrate how a CNN segmentation model can be used as a lightweight adapter for a frozen ViT feature encoder. Our novel feature adapter uses cross-attention modules that merge the multiscale features derived from the CNN encoder with feature embeddings from ViT, ensuring integration of the global insights from ViT along with local information from CNN. RESULTS: Extensive experiments demonstrate our method outperforms current models in surgical instrument segmentation. Specifically, it achieves superior performance in binary segmentation on the Robust-MIS 2019 dataset, as well as in multiclass segmentation tasks on the EndoVis 2017 and EndoVis 2018 datasets. It also showcases remarkable robustness through cross-dataset validation across these 3 datasets, along with the CholecSeg8k and AutoLaparo datasets. Ablation studies based on the datasets prove the efficacy of our novel adapter module. CONCLUSION: In this study, we presented a novel approach integrating ViT and CNN. Our unique feature adapter successfully combines the global insights of ViT with the local, multi-scale spatial capabilities of CNN. This integration effectively overcomes data limitations in surgical instrument segmentation. The source code is available at: https://github.com/weimengmeng1999/AdapterSIS.git .


Asunto(s)
Redes Neurales de la Computación , Humanos , Instrumentos Quirúrgicos , Procesamiento de Imagen Asistido por Computador/métodos , Cirugía Asistida por Computador/métodos
20.
J Conserv Dent Endod ; 27(4): 429-433, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38779213

RESUMEN

Background: This study aimed to detect the efficiency of anti-retraction adapter (ARA) attached to a handpiece (HP). Materials and Methods: Two types of dental HP with and without the ARA were used in this study. A total of 30 sets of samples were obtained from two groups and were subjected to a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and microbial culture for quantitative analysis of total bacterial and Legionella count. Statistical Analysis Used: The data obtained were tabulated using the Statistical Package for the Social Sciences (SPSS, IBM version 26.0) for statistical analysis. Results: The water samples were analyzed using PCR, Legionella-specific PCR, and culture-based analysis. In Groups 1 and 2, there was no significant difference between bacterial load in the water samples taken from both HP and coupling of the Dental Unit Waterline (DUWL). Conclusions: The reduction in bacterial load in DUWLs analyzed using quantitative RT-PCR was similar in both experimental groups. Overall, the bacterial load was lower in the group with ARA when compared to the group without ARA but not statistically significant. ARA was not effective in reducing the Legionella species load in DUWLs.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA