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1.
Artículo en Inglés | MEDLINE | ID: mdl-39011513

RESUMEN

Papillary adenomas, known precursors to papillary adenocarcinoma, warrant close monitoring due to their malignant potential. Historically, surgical resection represented the mainstay of treatment for papillary adenomas with intraductal extension. However, recent advancements in endoscopic techniques have facilitated the adoption of endoscopic papillectomy as a minimally invasive alternative in carefully selected cases. We report a case of an 82-year-old woman with a diagnosis of papillary adenoma exhibiting intraductal extension. This was managed with a novel endoscopic technique, balloon catheter-assisted endoscopic resection. Due to the obscured intraductal component of the papillary mass, a balloon occlusion catheter was deployed within the common bile duct and used as traction to facilitate endoscopic visualization of the mass. Endoscopic resection via papillectomy was subsequently performed. Histopathological examination of the resected specimen revealed a villous adenoma with high-grade dysplasia. Serial endoscopic ultrasound examinations with targeted papillary biopsies were performed to monitor for disease recurrence.

3.
Biomed Pharmacother ; 177: 117080, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38972151

RESUMEN

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.

4.
BMC Med Genomics ; 17(1): 168, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907304

RESUMEN

BACKGROUND: Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. METHODS: The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. RESULTS: The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. CONCLUSION: COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.


Asunto(s)
Adenocarcinoma , Colágeno Tipo IV , Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/inmunología , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/inmunología , Pronóstico , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Masculino , Femenino , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Estimación de Kaplan-Meier
5.
Nat Commun ; 15(1): 4684, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824184

RESUMEN

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.

6.
Heliyon ; 10(11): e31296, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38828311

RESUMEN

Acute pancreatitis (AP) is an inflammatory disease characterized by localized pancreatic injury and a systemic inflammatory response. Fatty acids (FAs), produced during the breakdown of triglycerides (TGs) in blood and peripancreatic fat, escalate local pancreatic inflammation to a systemic level by damaging pancreatic acinar cells (PACs) and triggering M1 macrophage polarization. This paper provides a comprehensive analysis of lipases' roles in the onset and progression of AP, as well as the effects of long-chain fatty acids (LCFAs) on the function of pancreatic acinar cells (PACs). Abnormalities in the function of PACs include Ca2+ overload, premature trypsinogen activation, protein kinase C (PKC) expression, endoplasmic reticulum (ER) stress, and mitochondrial and autophagic dysfunction. The study highlights the contribution of long-chain saturated fatty acids (LC-SFAs), especially palmitic acid (PA), to M1 macrophage polarization through the activation of the NLRP3 inflammasome and the NF-κB pathway. Furthermore, we investigated lipid lowering therapy for AP. This review establishes a theoretical foundation for pro-inflammatory mechanisms associated with FAs in AP and facilitating drug development.

7.
Front Cell Infect Microbiol ; 14: 1380998, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881734

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 , Inflamación
8.
Front Immunol ; 15: 1406538, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895124

RESUMEN

Inflammatory bowel disease (IBD) is a group of recurrent chronic inflammatory diseases, including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD has been extensively studied for decades, its cause and pathogenesis remain unclear. Existing research suggests that IBD may be the result of an interaction between genetic factors, environmental factors and the gut microbiome. IBD is closely related to non-coding RNAs (ncRNAs). NcRNAs are composed of microRNA(miRNA), long non-coding RNA(lnc RNA) and circular RNA(circ RNA). Compared with miRNA, the role of lnc RNA in IBD has been little studied. Lnc RNA is an RNA molecule that regulates gene expression and regulates a variety of molecular pathways involved in the pathbiology of IBD. Targeting IBD-associated lnc RNAs may promote personalized treatment of IBD and have therapeutic value for IBD patients. Therefore, this review summarized the effects of lnc RNA on the intestinal epithelial barrier, inflammatory response and immune homeostasis in IBD, and summarized the potential of lnc RNA as a biomarker of IBD and as a predictor of therapeutic response to IBD in the future.


Asunto(s)
Enfermedades Inflamatorias del Intestino , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Animales , Biomarcadores , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Regulación de la Expresión Génica , Microbioma Gastrointestinal
9.
Br J Pharmacol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38872396

RESUMEN

BACKGROUND AND PURPOSE: Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein-kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown. EXPERIMENTAL APPROACH: The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod-induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention. KEY RESULTS: Expression of Factor XII was markedly up-regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod-induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil-vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation. CONCLUSION AND IMPLICATIONS: Activation of Factor XII promoted psoriasis via prekallikrein-dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.

10.
J Nanobiotechnology ; 22(1): 286, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796465

RESUMEN

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/metabolismo
11.
iScience ; 27(5): 109272, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38706868

RESUMEN

For a long time, myeloid-derived suppressor cells (MDSCs) dilated in circulation system of colorectal cancer (CRC) patients have been puzzling clinicians. Various evidence shows that MDSCs constitute the bulk of immunosuppression in CRC, which is related to tumor growth, adhesion, invasion, metastasis, and immune escape. However, the mechanisms underlying these cells formation remain incompletely understood. In this study, we reported that CRC cell-derived LC3-dependent extracellular vesicles (LDEVs)-mediated M-MDSCs formation via TLR2-MYD88 pathway. Furthermore Hsp60 was the LDEVs surface ligand that triggered these MDSCs induction. In clinical studies, we reported that accumulation of circulating M-MDSCs as well as IL-10 and arginase1 secretion were reliant upon the levels of tumor cell-derived LDEVs in CRC patients. These findings indicated how local tumor cell-derived extracellular vesicles influence distal hematopoiesis and provided novel justification for therapeutic targeting of LDEVs in patients with CRC.

12.
Sensors (Basel) ; 24(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38732918

RESUMEN

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.

13.
Cell Death Discov ; 10(1): 242, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773098

RESUMEN

Abnormal activation of ferroptosis worsens the severity of acute pancreatitis and intensifies the inflammatory response and organ damage, but the detailed underlying mechanisms are unknown. Compared with other types of pancreatitis, hyperlipidemic acute pancreatitis (HLAP) is more likely to progress to necrotizing pancreatitis, possibly due to peripancreatic lipolysis and the production of unsaturated fatty acids. Moreover, high levels of unsaturated fatty acids undergo lipid peroxidation and trigger ferroptosis to further exacerbate inflammation and worsen HLAP. This paper focuses on the malignant development of hyperlipidemic pancreatitis with severe disease combined with the core features of ferroptosis to explore and describe the mechanism of this phenomenon and shows that the activation of lipid peroxidation and the aberrant intracellular release of many inflammatory mediators during ferroptosis are the key processes that regulate the degree of disease development in patients with HLAP. Inhibiting the activation of ferroptosis effectively reduces the intensity of the inflammatory response, thus reducing organ damage in patients and preventing the risk of HLAP exacerbation. Additionally, this paper summarizes the key targets and potential therapeutic agents of ferroptosis associated with HLAP deterioration to provide new ideas for future clinical applications.

14.
Appl Opt ; 63(9): 2218-2226, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38568575

RESUMEN

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.

15.
Front Neurol ; 15: 1365465, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38682033

RESUMEN

Objective: This retrospective study aimed to investigate the clinical features of optic neuritis associated with COVID-19 (COVID-19 ON), comparing them with neuromyelitis optica-associated optic neuritis (NMO-ON), myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON), and antibody-negative optic neuritis (antibody-negative ON). Methods: Data from 117 patients (145 eyes) with optic neuritis at the Shantou International Eye Center (March 2020-June 2023) were categorized into four groups based on etiology: Group 1 (neuromyelitis optica-related optic neuritis, NMO-ON), Group 2 (myelin oligodendrocyte glycoprotein optic neuritis, MOG-ON), Group 3 (antibody-negative optic neuritis, antibody-negative ON), and Group 4 (optic neuritis associated with COVID-19, COVID-19 ON). Characteristics of T2 and enhancement in orbital magnetic resonance imaging (MRI) were assessed. Best-corrected visual acuity (BCVA) was compared before treatment, at a short-term follow-up (14 days), and at the last follow-up after treatment. Results: The COVID-19-associated optic neuritis (COVID-19 ON) group exhibited 100% bilateral involvement, significantly surpassing other groups (P < 0.001). Optic disk edema was observed in 100% of COVID-19 ON cases, markedly differing from neuromyelitis optica-related optic neuritis (NMO-ON) (P = 0.023). Orbital magnetic resonance imaging (MRI) revealed distinctive long-segment lesions without intracranial involvement in T1-enhanced sequences for the COVID-19 ON group compared to the other three groups (P < 0.001). Discrepancies in optic nerve sheath involvement were noted between the COVID-19 ON group and both NMO-ON and antibody-negative optic neuritis (antibody-negative ON) groups (P = 0.028). Before treatment, no significant difference in best-corrected visual acuity (BCVA) existed between the COVID-19 ON group and other groups. At the 14-day follow-up, BCVA in the COVID-19 ON group outperformed the NMO-ON (P < 0.001) and antibody-negative ON (P = 0.028) groups, with no significant difference observed compared to the myelin oligodendrocyte glycoprotein optic neuritis (MOG-ON) group. At the last follow-up after treatment, BCVA in the COVID-19 ON group significantly differed from the NMO-ON group (P < 0.001). Conclusion: Optic neuritis associated with COVID-19 (COVID-19 ON) predominantly presents with bilateral onset and optic disk edema. Orbital magnetic resonance imaging (MRI) demonstrates that COVID-19 ON presents as long-segment enhancement without the involvement of the intracranial segment of the optic nerve in T1-enhanced images. Glucocorticoid therapy showed positive outcomes.

16.
Sensors (Basel) ; 24(8)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38676171

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.

17.
Sensors (Basel) ; 24(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38676208

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.

18.
Technol Cancer Res Treat ; 23: 15330338241239139, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38613350

RESUMEN

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 ADAM
19.
J Orthop Surg Res ; 19(1): 232, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38594698

RESUMEN

BACKGROUND: For knee osteoarthritis patients, analyzing alignment of lower limbs is essential for therapy, which is currently measured from standing long-leg radiographs of anteroposterior X-ray (LLR) manually. To address the time wasting, poor reproducibility and inconvenience of use caused by existing methods, we present an automated measurement model in portable devices for assessing knee alignment from LLRs. METHOD: We created a model and trained it with 837 conforming LLRs, and tested it using 204 LLRs without duplicates in a portable device. Both manual and model measurements were conducted independently, then we recorded knee alignment parameters such as Hip knee ankle angle (HKA), Joint line convergence angle (JCLA), Anatomical mechanical angle (AMA), mechanical Lateral distal femoral angle (mLDFA), mechanical Medial proximal tibial angle (mMPTA), and the time required. We evaluated the model's performance compared with manual results in various metrics. RESULT: In both the validation and test sets, the average mean radial errors were 2.778 and 2.447 (P<0.05). The test results for native knee joints showed that 92.22%, 79.38%, 87.94%, 79.82%, and 80.16% of the joints reached angle deviation<1° for HKA, JCLA, AMA, mLDFA, and mMPTA. Additionally, for joints with prostheses, 90.14%, 93.66%, 86.62%, 83.80%, and 85.92% of the joints reached that. The Chi-square test did not reveal any significant differences between the manual and model measurements in subgroups (P>0.05). Furthermore, the Bland-Altman 95% limits of agreement were less than ± 2° for HKA, JCLA, AMA, and mLDFA, and slightly more than ± 2 degrees for mMPTA. CONCLUSION: The automatic measurement tool can assess the alignment of lower limbs in portable devices for knee osteoarthritis patients. The results are reliable, reproducible, and time-saving.


Asunto(s)
Aprendizaje Profundo , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Reproducibilidad de los Resultados , Extremidad Inferior/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Tibia , Fémur , Estudios Retrospectivos
20.
Biomater Res ; 28: 0016, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628309

RESUMEN

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.

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