RESUMEN
BACKGROUND AND AIM: This study aims to determine whether endoscopic papillectomy (EP) is a safe and effective treatment for early duodenal papillary carcinoma with long-term follow-up. METHODS: From June 2012 to September 2022, 48 patients with early duodenal papilloma carcinoma who received endoscopic treatment were included. The histological types, percentage of complete resections, postoperative residuals, adverse events, and recurrences were evaluated. RESULTS: EP was successful in all patients; 46 were lumped, and two were fragmented, with a 95.8% intact removal rate (46/48). The preoperative biopsy pathological positive rate was 70.8% (34/48). The incidence of early postoperative adverse events (within 1 month after EP) were 16.7% (8/48), including four cases of acute pancreatitis, three cases of delayed bleeding, and one case of acute cholangitis. In addition, 4.2% (2/48) of the late adverse events were bile duct stenosis. After 6 months, the postoperative residual rate was 0%. The median time to recurrence was 17.5 months, and the postoperative recurrence rate was 16.7% (8/48) in patients treated with radiofrequency ablation. The median progression-free survival was 18.6 months (95% CI, 12.1-25.1), and the median overall survival was 121.5 months (95% CI, 105.6-120.9). CONCLUSIONS: EP is a safe and efficient alternative therapy for early duodenal papillary carcinoma. Endoscopic follow-up and treatment are essential because of the potential for recurrence.
Asunto(s)
Neoplasias Duodenales , Humanos , Masculino , Femenino , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/patología , Neoplasias Duodenales/mortalidad , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Factores de Tiempo , Carcinoma Papilar/cirugía , Carcinoma Papilar/patología , Carcinoma Papilar/mortalidad , Estudios de Seguimiento , Adulto , Recurrencia Local de Neoplasia , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Anciano de 80 o más AñosRESUMEN
Various clinical symptoms of digestive system, such as infectious, inflammatory, and malignant disorders, have a profound impact on the quality of life and overall health of patients. Therefore, the chase for more potent medicines is both highly significant and urgent. Nanozymes, a novel class of nanomaterials, amalgamate the biological properties of nanomaterials with the catalytic activity of enzymes, and have been engineered for various biomedical applications, including complex gastrointestinal diseases (GI). Particularly, because of their distinctive metal coordination structure and ability to maximize atom use efficiency, single-atom nanozymes (SAzymes) with atomically scattered metal centers are becoming a more viable substitute for natural enzymes. Traditional nanozyme design strategies are no longer able to meet the current requirements for efficient and diverse SAzymes design due to the diversification and complexity of preparation processes. As a result, this review emphasizes the design concept and the synthesis strategy of SAzymes, and corresponding bioenzyme-like activities, such as superoxide dismutase (SOD), peroxidase (POD), oxidase (OXD), catalase (CAT), and glutathione peroxidase (GPx). Then the various application of SAzymes in GI illnesses are summarized, which should encourage further research into nanozymes to achieve better application characteristics.
Asunto(s)
Enfermedades Gastrointestinales , Nanoestructuras , Humanos , Nanoestructuras/química , Animales , Enzimas/química , Enzimas/metabolismo , Superóxido Dismutasa/química , Superóxido Dismutasa/metabolismo , Catalasa/química , Catalasa/metabolismo , Catálisis , Glutatión Peroxidasa/metabolismoRESUMEN
This paper introduces an optical-mechanical system designed for the dynamic detection and analysis of lunar dust, typically characterized as particles under 20 micrometers on the lunar surface. The system's design is both compact and lightweight, aligning with the payload constraints of lunar exploration missions. It is capable of real-time tracking and recording the motion of lunar dust at various altitudes, a crucial capability for understanding the environmental dynamics of the lunar surface. By capturing images and applying sophisticated algorithms, the system accurately measures the velocity and size of dust particles. This approach significantly advances the quantitative analysis of lunar dust, especially during agitation events, filling a critical gap in our current understanding of lunar surface phenomena. The insights gained from this study are not only pivotal for developing theoretical models of lunar surface air flow disturbances and dust movement but also instrumental in designing effective dust mitigation and hazard avoidance strategies for future lunar missions, thereby enhancing both scientific knowledge and the engineering applications in lunar exploration.
RESUMEN
BACKGROUND AND PURPOSE: The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION). MATERIALS AND METHODS: This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7-14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement. RESULTS: No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7-14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045). CONCLUSION: Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.
Asunto(s)
Glucocorticoides , Neuropatía Óptica Isquémica , Humanos , Prednisona/uso terapéutico , Neuropatía Óptica Isquémica/tratamiento farmacológico , Estudios Retrospectivos , MetilprednisolonaRESUMEN
BACKGROUND: Endoscopic mucosal resection (EMR) appears to be a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. To assess the effectiveness and safety of EMR for removing SSPs ≥ 10 mm, we conducted this systematic review and meta-analysis. METHODS: We conducted a thorough search of Embase, PubMed, Cochrane, and Web of Science databases for relevant studies reporting on EMR of SSPs ≥ 10 mm, up until December 2023. Our primary endpoints of interest were rates of technical success, residual SSPs, and adverse events (AE). RESULTS: Our search identified 426 articles, of which 14 studies with 2262 SSPs were included for analysis. The rates of technical success, AEs, and residual SSPs were 100%, 2.0%, and 3.1%, respectively. Subgroup analysis showed that the technical success rates were the same for polyps 10-19 and 20 mm, and en-bloc and piecemeal resection. Residual SSPs rates were similar in en-bloc and piecemeal resection, but much lower in cold EMR (1.0% vs. 4.2%, P = 0.034). AEs rates were reduced in cold EMR compared to hot EMR (0% vs. 2.9%, P = 0.168), in polyps 10-19 mm compared to 20 mm (0% vs. 4.1%, P = 0.255), and in piecemeal resection compared to en-bloc (0% vs. 0.7%, P = 0.169). CONCLUSIONS: EMR is an effective and safe technique for removing SSPs ≥ 10 mm. The therapeutic effect of cold EMR is superior to that of hot EMR, with a lower incidence of adverse effects. PROSPERO REGISTRATION NUMBER: CRD42023388959.
Asunto(s)
Pólipos del Colon , Resección Endoscópica de la Mucosa , Humanos , Resección Endoscópica de la Mucosa/métodos , Pólipos del Colon/cirugía , Pólipos del Colon/patología , Resultado del TratamientoRESUMEN
In this paper, we consider a low-latency Mobile Edge Computing (MEC) network where multiple User Equipment (UE) wirelessly reports to a decision-making edge server. At the same time, the transmissions are operated with Finite Blocklength (FBL) codes to achieve low-latency transmission. We introduce the task of Age upon Decision (AuD) aimed at the timeliness of tasks used for decision-making, which highlights the timeliness of the information at decision-making moments. For the case in which dynamic task generation and random fading channels are considered, we provide a task AuD minimization design by jointly selecting UE and allocating blocklength. In particular, to solve the task AuD minimization problem, we transform the optimization problem to a Markov Decision Process problem and propose an Error Probability-Controlled Action-Masked Proximal Policy Optimization (EMPPO) algorithm. Via simulation, we show that the proposed design achieves a lower AuD than baseline methods across various network conditions, especially in scenarios with significant channel Signal-to-Noise Ratio (SNR) differences and low average SNR, which shows the robustness of EMPPO and its potential for real-time applications.
RESUMEN
In the context of Industry 4.0, industrial production equipment needs to communicate through the industrial internet to improve the intelligence of industrial production. This requires the current communication network to have the ability of large-scale equipment access, multiple communication protocols/heterogeneous systems interoperability, and end-to-end deterministic low-latency transmission. Time-sensitive network (TSN), as a new generation of deterministic Ethernet communication technology, is the main development direction of time-critical communication technology applied in industrial environments, and Wi-Fi technology has become the main way of wireless access for users due to its advantages of high portability and mobility. Therefore, accessing WiFi in the TSN is a major development direction of the current industrial internet. In this paper, we model the scheduling problem of TSN and WiFi converged networks and propose a scheme based on a greedy strategy distributed estimation algorithm (GE) to solve the scheduling problem. Compared with the integer linear programming (ILP) algorithm and the Tabu algorithm, the algorithm implemented in this paper outperforms the other algorithms in being able to adapt to a variety of different scenarios and in scheduling optimization efficiency, especially when the amount of traffic to be deployed is large.
RESUMEN
The era of Industry 4.0 is gradually transforming our society into a data-driven one, which can help us uncover valuable information from accumulated data, thereby improving the level of social governance. The detection of anomalies, is crucial for maintaining societal trust and fairness, yet it poses significant challenges due to the ubiquity of anomalies and the difficulty in identifying them accurately. This paper aims to enhance the performance of the current Graph Convolutional Network (GCN)-based Graph Anomaly Detection (GAD) algorithm on datasets with extremely low proportions of anomalous labels. This goal is achieved through modifying the GCN network structure and conducting feature extraction, thus fully utilizing three types of information in the graph: node label information, node feature information, and edge information. Firstly, we theoretically demonstrate the relationship between label propagation and feature convolution, indicating that the Label Propagation Algorithm (LPA) can serve as a regularization penalty term for GCN, aiding in training and enabling learnable edge weights, providing a basis for incorporating node label information into GCN networks. Secondly, we introduce a method to aggregate node and edge features, thereby incorporating edge information into GCN networks. Finally, we design different GCN trainable weights for node features and co-embedding features. This design allows different features to be projected into different spaces, greatly enhancing model expressiveness. Experimental results on the DGraph dataset demonstrate superior AUC performance compared to baseline models, highlighting the feasibility and efficacy of the proposed approach in addressing GAD tasks in the scene with extremely low proportions of anomalous data.
Asunto(s)
Neoplasias de los Conductos Biliares , Terapia por Láser , Humanos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Terapia por Láser/métodos , Endoscopía del Sistema Digestivo/métodos , Masculino , Conductos Biliares Intrahepáticos/cirugía , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Anciano , Femenino , Carcinoma Papilar/cirugía , Carcinoma Papilar/diagnóstico por imagen , Colangiopancreatografia Retrógrada Endoscópica/métodosRESUMEN
Miniaturized passive fliers based on smart materials face challenges in precise control of shape-morphing for aerodynamics and contactless modulation of diverse gliding modes. Here, we present the optical control of gliding performances in azobenzene-crosslinked liquid crystal networks films through photochemical actuation, enabling reversible and bistable shape-morphing. First, an actuator film is integrated with additive constructs to form a rotating glider, inspired by the natural maple samara, surpassing natural counterparts in reversibly optical tuning of terminal velocity, rotational rate, and circling position. We demonstrate optical modulation dispersion of landing points for the photo-responsive microfliers indoors and outdoors. Secondly, we show the scalability of polymer film geometry for miniature gliders with similar light tunability. Thirdly, we extend the material platform to other three gliding modes: Javan cucumber seed-like glider, parachute and artificial dandelion seed. The findings pave the way for distributed microflier with contactless flight dynamics control.
RESUMEN
Background/Aim: We employed Mendelian randomization (MR) analysis to investigate the causal relationship between the gut microbiota, acute pancreatitis, and potential inflammatory proteins. Methods: The data for gut microbiota, acute pancreatitis, and inflammatory proteins are sourced from public databases. We conducted a bidirectional MR analysis to explore the causal relationship between gut microbiota and acute pancreatitis, and employed a two-step MR analysis to identify potential mediating inflammatory proteins. IVW is the primary analysis method, heterogeneity, pleiotropy, and sensitivity analyses were also conducted simultaneously. Results: We identified five bacterial genera associated with the risk of acute pancreatitis, namely genus.Coprococcus3, genus.Eubacterium fissicatena group, genus.Erysipelotrichaceae UCG-003, genus.Fusicatenibacter, and genus.Ruminiclostridium6. Additionally, we have discovered three inflammatory proteins that are also associated with the occurrence of acute pancreatitis, namely interleukin-15 receptor subunit alpha (IL-15RA), monocyte chemoattractant protein-4 (CCL13), and tumor necrosis factor receptor superfamily member 9 (TNFRSF9). Following a two-step MR analysis, we ultimately identified IL-15RA as a potential intermediate factor, with a mediated effect of 0.018 (95% CI: 0.005 - 0.032). Conclusion: Our results support the idea that genus.Coprococcus3 promotes the occurrence of acute pancreatitis through IL-15RA. Furthermore, there is a potential causal relationship between the gut microbiota, inflammatory proteins, and acute pancreatitis. These findings provide new insights for subsequent acute pancreatitis prevention.
Asunto(s)
Microbioma Gastrointestinal , Análisis de la Aleatorización Mendeliana , Pancreatitis , Pancreatitis/microbiología , Humanos , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , InflamaciónRESUMEN
BACKGROUND: Cuproptosis is a novel type of mediated cell death strongly associated with the progression of several cancers and has been implicated as a potential therapeutic target. However, the role of cuproptosis in cholangiocarcinoma for prognostic prediction, subgroup classification, and therapeutic strategies remains largely unknown. METHODS: A systematic analysis was conducted among 146 cuproptosis-related genes and clinical information based on independent mRNA and protein datasets to elucidate the potential mechanisms and prognostic prediction value of cuproptosis-related genes. A 10-cuproptosis-related gene prediction model was constructed, and its effects on cholangiocarcinoma prognosis were significantly connected to poor patient survival. Additionally, the expression patterns of our model included genes that were validated with several cholangiocarcinoma cancer cell lines and a normal biliary epithelial cell line. RESULTS: First, a 10-cuproptosis-related gene signature (ADAM9, ADAM17, ALB, AQP1, CDK1, MT2A, PAM, SOD3, STEAP3, and TMPRSS6) displayed excellent predictive performance for the overall survival of cholangiocarcinoma. The low-cuproptosis group had a significantly better prognosis than the high-cuproptosis group with transcriptome and protein cohorts. Second, compared with the high-risk and low-risk groups, the 2 groups displayed distinct tumor microenvironments, reduced proportions of endothelial cells, and increased levels of cancer-associated fibroblasts based on CIBERSORTx and EPIC analyses. Third, patients' sensitivities to chemotherapeutic drugs and immune checkpoints revealed distinctive differences between the 2 groups. Finally, in replicating the expression patterns of the 10 genes, these results were validated with quantitative real-time polymerase chain reaction results validating the abnormal expression pattern of the target genes in cholangiocarcinoma. CONCLUSIONS: Collectively, we established and verified an effective prognostic model that could separate cholangiocarcinoma patients into 2 heterogeneous cuproptosis subtypes based on the molecular or protein characteristics of 10 cuproptosis-related genes. These findings may provide potential benefits for unveiling molecular characteristics and defining subgroups could improve the early diagnosis and individualized treatment of cholangiocarcinoma patients.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Células Endoteliales , Pronóstico , Colangiocarcinoma/genética , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos , Microambiente Tumoral/genética , Proteínas de la Membrana , Proteínas ADAMRESUMEN
Tissue damage and functional abnormalities in organs have become a considerable clinical challenge. Organoids are often applied as disease models and in drug discovery and screening. Indeed, several studies have shown that organoids are an important strategy for achieving tissue repair and biofunction reconstruction. In contrast to established stem cell therapies, organoids have high clinical relevance. However, conventional approaches have limited the application of organoids in clinical regenerative medicine. Engineered organoids might have the capacity to overcome these challenges. Bioengineering-a multidisciplinary field that applies engineering principles to biomedicine-has bridged the gap between engineering and medicine to promote human health. More specifically, bioengineering principles have been applied to organoids to accelerate their clinical translation. In this review, beginning with the basic concepts of organoids, we describe strategies for cultivating engineered organoids and discuss the multiple engineering modes to create conditions for breakthroughs in organoid research. Subsequently, studies on the application of engineered organoids in biofunction reconstruction and tissue repair are presented. Finally, we highlight the limitations and challenges hindering the utilization of engineered organoids in clinical applications. Future research will focus on cultivating engineered organoids using advanced bioengineering tools for personalized tissue repair and biofunction reconstruction.
RESUMEN
PURPOSE: To obtain performance values of PET/CT for determining the nodal status of rectal cancer. MATERIALS: A comprehensive literature search was performed on PubMed and Embase for original diagnostic accuracy studies on the diagnostic performance of PET-CT for detection of LN metastasis in rectal cancer. The QUADAS-2 was used to evaluate the methodological quality of each study. Pooled sensitivity, specificity, and AUC were calculated to estimate the diagnostic role of PET/CT using a random-effects model. A subgroup analysis was performed to investigate the influence of different parameters on diagnostic performance. RESULTS: A total of 15 studies and 1209 patients were included. A publication bias was observed. The pooled sensitivity, specificity, and AUC for PET/CT was 0.62 (95% CI 0.49, 0.74), 0.94 (95% CI 0.87, 0.97), and 0.87 (95% CI 0.83-0.89), respectively. Per-node basis yields higher accuracy than per-patient basis, with pooled sensitivities of 0.65 (95% CI 0.50-0.79) vs. 0.56 (95% CI 0.36-0.77) and specificities of 0.96 (95% CI 0.92-1.00) vs. 0.88 (95% CI 0.76-1.00), but there were no significant differences in diagnostic accuracy. CONCLUSION: PET/CT has high specificity but moderate sensitivity for the detection of LN metastasis in rectal cancer. The current data suggests that the diagnostic capabilities of this method is limited due to its moderate sensitivity.
Asunto(s)
Fluorodesoxiglucosa F18 , Metástasis Linfática , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Neoplasias del Recto , Sensibilidad y Especificidad , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Metástasis Linfática/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patologíaRESUMEN
Cholangiocarcinoma (CCA) is becoming more common and deadly worldwide. Tumor-infiltrating T cell subtypes make distinct contributions to the immune system; collectively, they constitute a significant portion of the tumor microenvironment (TME) in CCA. By secreting cytokines and other chemicals, regulatory T cells (Tregs) decrease activated T cell responses, acting as immunosuppressors. Reduced CD8+ T cell activation results in stimulating programmed death-1 (PD-1), which undermines the immunological homeostasis of T lymphocytes. On the other hand, cancer cells are eliminated by activated cytotoxic T lymphocyte (CTL) through the perforin-granzyme or Fas-FasL pathways. Th1 and CTL immune cell infiltration into the malignant tumor is also facilitated by γδ T cells. A higher prognosis is typically implied by CD8+ T cell infiltration, and survival is inversely associated with Treg cell density. Immune checkpoint inhibitors, either singly or in combination, provide novel therapeutic strategies for CCA immunotherapy. Furthermore, it is anticipated that immunotherapeutic strategies-such as the identification of new immune targets, combination treatments involving several immune checkpoint inhibitors, and chimeric antigen receptor-T therapies (CAR-T)-will optimize the effectiveness of anti-CCA treatments while reducing adverse effects.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Inmunoterapia , Linfocitos Infiltrantes de Tumor , Escape del Tumor , Microambiente Tumoral , Humanos , Colangiocarcinoma/inmunología , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Neoplasias de los Conductos Biliares/inmunología , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Escape del Tumor/efectos de los fármacos , Escape del Tumor/inmunología , Animales , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Linfocitos T Reguladores/inmunologíaRESUMEN
BACKGROUND: The distally fixed stem used in revision total hip arthroplasty (rTHA) with extended trochanteric osteotomy (ETO) is subject to periprosthetic fracture, stem subsidence, and stress shielding. The prospective multicentric study aimed to assess the clinical and radiographic outcomes, and complications of using the Corail revision stem in rTHA with ETO. METHODS: Sixty-four patients undergoing rTHA with ETO using the Corail revision stem between 2019 and 2020 were enrolled in the study. We performed a postoperative follow-up of the patient and obtained radiographs and Harris hip scores (HHSs). These results were used to analyze ETO union, Engh scores, bone remodeling, stem stability and hip function. RESULTS: The mean follow-up duration was 34 months (range 23-41). Sixty-two patients who underwent ETOs achieved complete healing at the final follow-up. Fifty-nine hips had bony ingrowth from the osteotomy fragment to the stem without radiolucent lines. The postoperative Engh score was 21.3 ± 3.59 (range 15.5-27.0). Forty-three hips had regeneration in the proximal femur. Two patients had transient thigh pain postoperatively. The postoperative HHS improved from 40.7 ± 16.67 (range 0-67) preoperatively to 82.1 ± 6.83 (range 73-93). CONCLUSION: Corail revision stems are a viable and reliable option in rTHA with ETO. This stem had excellent clinical and radiographic outcomes, resulting in a high rate of ETO union and stem survival. The revision stem enabled restoration of proximal bone stock in femurs with prerevision bone defects, which were prepared for the next revision operation. Level of evidence Level IIb, Prospective self-control study.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Durapatita , Estudios Prospectivos , Fémur/diagnóstico por imagen , Fémur/cirugía , Osteotomía/métodos , Reoperación/métodos , Estudios Retrospectivos , Diseño de Prótesis , Estudios de SeguimientoRESUMEN
Homograft rejection is the main cause of heart transplantation failure. The role of TLR2, a major member of the toll-like receptor (TLR) family, in transplantation rejection is has yet to be elucidated. In this study, we used a mouse model of acute cardiac transplantation rejection to investigate whether the TLR2 signalling pathway can regulate cardiac transplantation rejection by regulating alloreactive IL-17+γδT (γδT17) cells. We found that the expression of TLR2 on the surface of dendritic cells (DCs) and macrophages increased during acute transplantation rejection. In addition, our investigation revealed that γδT17 cells exert a significant influence on acute cardiac transplantation rejection. TLR2 gene knockout resulted in an increase in alloreactive γδT17 cells in the spleen and heart grafts of recipient mice compared with wild-type recipient mice and an increase in the mRNA expression of IL-17, IL-1ß, CCR6, and CCL20 in the heart grafts. In an in vitro experiment, a mixed lymphocyte reaction was conducted to assess the impact of TLR2 deficiency on the generation of γδT17 cells, which further substantiated a significant increase compared to that in wild-type controls. Furthermore, the mixed lymphocyte reaction showed that TLR2 regulated the production of γδT17 cells by regulating the ability of DCs to secrete IL-1ß. These results suggest that TLR2 signalling is important for regulating the generation of γδT17 cells after cardiac allograft transplantation.
Asunto(s)
Trasplante de Corazón , Linfocitos Intraepiteliales , Receptor Toll-Like 2 , Animales , Ratones , Rechazo de Injerto , Interleucina-17/genética , Interleucina-17/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Trasplante Homólogo , Linfocitos Intraepiteliales/inmunologíaRESUMEN
The Lithosphere-Asthenosphere Boundary (LAB) beneath oceanic plates is generally imaged as a sharp seismic velocity reduction, suggesting the presence of partial melts. However, the fate of a melt-rich LAB is unclear after these plates descend into the mantle at subduction zones. Recent geophysical studies suggest its persistence with down-going old and cold slabs, but whether or not it is commonly present remains unclear, especially for young and warm slabs such as in the Cascadia subduction zone. Here we provide evidence for its presence at Cascadia in the form of a large (9.8 ± 1.5 % ) decrease in shear-wave velocity over a very small (<3 km) depth interval. Similarly large and sharp seismic velocity reduction at the bottom of both old and young slabs, as well as along the base of oceanic plates before subduction, possibly represents widespread presence of melts. The melt-rich sub-slab LAB may strongly influence subduction dynamics and viscoelastic earthquake cycles.