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1.
Thorac Cancer ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984426

RESUMO

Anti-gamma-aminobutyric acid receptor type A (GABAA) encephalitis is a relatively rare autoimmune encephalitis, and often associated with thymoma. Here, a 44-year-old female was diagnosed as having a thymoma with autoimmune encephalitis. At 4-month follow-up she was without recurrence of symptoms after treatment with methylprednisolone pulse therapy and immunotherapy. This case report provides a reference for the identification of this type of paraneoplastic encephalitis and for a therapeutic schedule. It also highlights that conservative treatment may be effective for patients with a tumor and GABAA encephalitis.

2.
Nat Commun ; 15(1): 5498, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38944647

RESUMO

IncX3 plasmids carrying the New Delhi metallo-ß-lactamase-encoding gene, blaNDM-5, are rapidly spreading globally in both humans and animals. Given that carbapenems are listed on the WHO AWaRe watch group and are prohibited for use in animals, the drivers for the successful dissemination of Carbapenem-Resistant Enterobacterales (CRE) carrying blaNDM-5-IncX3 plasmids still remain unknown. We observe that E. coli carrying blaNDM-5-IncX3 can persist in chicken intestines either under the administration of amoxicillin, one of the largest veterinary ß-lactams used in livestock, or without any antibiotic pressure. We therefore characterise the blaNDM-5-IncX3 plasmid and identify a transcription regulator, VirBR, that binds to the promoter of the regulator gene actX enhancing the transcription of Type IV secretion systems (T4SS); thereby, promoting conjugation of IncX3 plasmids, increasing pili adhesion capacity and enhancing the colonisation of blaNDM-5-IncX3 transconjugants in animal digestive tracts. Our mechanistic and in-vivo studies identify VirBR as a major factor in the successful spread of blaNDM-5-IncX3 across one-health AMR sectors. Furthermore, VirBR enhances the plasmid conjugation and T4SS expression by the presence of copper and zinc ions, thereby having profound ramifications on the use of universal animal feeds.


Assuntos
Antibacterianos , Galinhas , Conjugação Genética , Escherichia coli , Plasmídeos , beta-Lactamases , Animais , Plasmídeos/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Galinhas/microbiologia , Humanos , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Sistemas de Secreção Tipo IV/genética , Sistemas de Secreção Tipo IV/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Amoxicilina/farmacologia , Regiões Promotoras Genéticas/genética , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/transmissão , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Intestinos/microbiologia
3.
Small ; : e2309907, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712486

RESUMO

The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.

4.
Phys Life Rev ; 50: 13-26, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38821019

RESUMO

The gut immune system embodies a complex interplay between the gut mucosal barrier, the host's immune cells, and gut microbiota. These components exist within a dynamic environment characterized by a variety of physical cues, e.g., compression, tension, shear stress, stiffness, and viscoelasticity. The physical cues can be modified under specific pathological conditions. Given their dynamic nature, comprehending the specific effects of these physical cues on the gut immune system is critical for pathological and therapeutic studies of intestinal immune-related diseases. This review aims to discuss how physical cues influence gut immunology by affecting the gut mucosal barrier, host immune cells, and gut microbiota, defining this concept as gut mechanoimmunology. This review seeks to highlight that an enhanced understanding of gut mechanoimmunology carries therapeutic implications, not only for intestinal diseases but also for extraintestinal diseases.

5.
Cancer Med ; 13(10): e7245, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38785171

RESUMO

BACKGROUNDS: Platelet-to-albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. METHODS: A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms-one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. RESULTS: Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune-Inflammation Index (SII), platelet-to-lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five-cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. CONCLUSIONS: PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life.


Assuntos
Cistite , Nomogramas , Lesões por Radiação , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia , Cistite/etiologia , Cistite/diagnóstico , Cistite/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Lesões por Radiação/sangue , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Adulto , Idoso , Fatores de Risco , Biomarcadores/sangue , Inflamação/sangue , Plaquetas/patologia , Contagem de Plaquetas , Albumina Sérica/análise , Prognóstico
6.
Pathogens ; 13(5)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38787278

RESUMO

Human fungal diseases are infections caused by any fungus that invades human tissues, causing superficial, subcutaneous, or systemic diseases. Fungal infections that enter various human tissues and organs pose a significant threat to millions of individuals with weakened immune systems globally. Over recent decades, the reported cases of invasive fungal infections have increased substantially and research progress in this field has also been rapidly boosted. This review provides a comprehensive list of human fungal pathogens extracted from over 850 recent case reports, and a summary of the relevant disease conditions and their origins. Details of 281 human fungal pathogens belonging to 12 classes and 104 genera in the divisions ascomycota, basidiomycota, entomophthoromycota, and mucoromycota are listed. Among these, Aspergillus stands out as the genus with the greatest potential of infecting humans, comprising 16 species known to infect humans. Additionally, three other genera, Curvularia, Exophiala, and Trichophyton, are recognized as significant genera, each comprising 10 or more known human pathogenic species. A phylogenetic analysis based on partial sequences of the 28S nrRNA gene (LSU) of human fungal pathogens was performed to show their phylogenetic relationships and clarify their taxonomies. In addition, this review summarizes the recent advancements in fungal disease diagnosis and therapeutics.

7.
Front Genet ; 15: 1392518, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803545

RESUMO

Objective: Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear. Methods: We explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results. Results: We found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320-2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291-2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295-1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008-1.078, p = 0.0157). Conclusion: Our study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

8.
MycoKeys ; 104: 9-50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665970

RESUMO

This article presents the results of an ongoing inventory of Ascomycota in Yunnan, China, carried out as part of the research project series "Exploring ascomycete diversity in Yunnan". From over 100 samples collected from diverse host substrates, microfungi have been isolated, identified and are currently being documented. The primary objective of this research is to promote the discovery of novel taxa and explore the ascomycete diversity in the region, utilising a morphology-phylogeny approach. This article represents the second series of species descriptions for the project and introduces three undocumented species found in the families Bambusicolaceae, Dictyosporiaceae and Periconiaceae, belonging to the suborder Massarineae (Pleosporales, Dothideomycetes). These novel taxa exhibit typical morphological characteristics of Bambusicola, Periconia and Trichobotrys, leading to their designation as Bambusicolahongheensis, Periconiakunmingensis and Trichobotryssinensis. Comprehensive multigene phylogenetic analyses were conducted to validate the novelty of these species. The results revealed well-defined clades that are clearly distinct from other related species, providing robust support for their placement within their respective families. Notably, this study unveils the phylogenetic affinity of Trichobotrys within Dictyosporiaceae for the first time. Additionally, the synanamorphism for the genus Trichobotrys is also reported for the first time. Detailed descriptions, illustrations and updated phylogenies of the novel species are provided, and thus presenting a valuable resource for researchers and mycologists interested in the diversity of ascomycetes in Yunnan. By enhancing our understanding of the Ascomycota diversity in this region, this research contributes to the broader field of fungal taxonomy and their phylogenetic understanding.

9.
Environ Sci Pollut Res Int ; 31(21): 31028-31041, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38619770

RESUMO

Lead is one of the primary pollutants found in water and poses significant toxicity risks to humans; thus, it is necessary to investigate techniques for removing it economically and efficiently. In order to enhance the removal capacity of Pb2+, coconut shell-based activated carbon (AC) was modified with introducing oxygen-containing functional groups (OFGs) via nitric acid (HNO3) or hydrogen peroxide (H2O2) modification in this study. The characterization results show that after oxidation treatment, the content of OFGs increased, and the textural properties of the samples do not change significantly. This indicates that the modification conditions used in this study effectively introduced OFGs while avoiding the adverse effects on physical adsorption ability of AC caused by oxidation treatment. The Pb2+ adsorption capacities of the AC modified with 10 M HNO3 and 30 wt.% H2O2 were 4.26 and 3.64 times that of the pristine AC, respectively. The experimental data can be well fitted using the Langmuir isotherm model and the Elovich kinetic model, suggesting that the adsorption of Pb2+ on AC belongs to single-layer adsorption, and chemical adsorption dominates the adsorption process. In summary, the hydrothermal-assisted HNO3/H2O2-modified coconut shell-based AC shows great potential in efficiently removing Pb2+ from solutions, offering a solution for utilizing coconut shell waste.


Assuntos
Carvão Vegetal , Chumbo , Oxigênio , Poluentes Químicos da Água , Adsorção , Chumbo/química , Carvão Vegetal/química , Oxigênio/química , Poluentes Químicos da Água/química , Cocos/química , Cinética , Peróxido de Hidrogênio/química , Carbono/química
10.
MedComm (2020) ; 5(4): e530, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576458

RESUMO

Currently, there is a lack of effective treatments for spinal cord injury (SCI), a debilitating medical condition associated with enduring paralysis and irreversible neuronal damage. Extradural decompression of osseous as well as soft tissue components has historically been the principal objective of surgical procedures. Nevertheless, this particular surgical procedure fails to tackle the intradural compressive alterations that contribute to secondary SCI. Here, we propose an early intrathecal decompression strategy and evaluate its role on function outcome, tissue sparing, inflammation, and tissue stiffness after SCI. Durotomy surgery significantly promoted recovery of hindlimb locomotor function in an open-field test. Radiological analysis suggested that lesion size and tissue edema were significantly reduced in animals that received durotomy. Relative to the group with laminectomy alone, the animals treated with a durotomy had decreased cavitation, scar formation, and inflammatory responses at 4 weeks after SCI. An examination of the mechanical properties revealed that durotomy facilitated an expeditious restoration of the injured tissue's elastic rigidity. In general, early decompressive durotomy could serve as a significant strategy to mitigate the impairments caused by secondary injury and establish a more conducive microenvironment for prospective cellular or biomaterial transplantation.

11.
Oncogene ; 43(21): 1631-1643, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38589675

RESUMO

Androgen deprivation therapy (ADT) is the first line of treatment for metastatic prostate cancer (PCa) that effectively delays the tumor progression. However, it also increases the risk of venous thrombosis event (VTE) in patients, a leading cause of mortality. How a pro-thrombotic cascade is induced by ADT remains poorly understood. Here, we report that protein disulfide isomerase A2 (PDIA2) is upregulated in PCa cells to promote VTE formation and enhance PCa cells resistant to ADT. Using various in vitro and in vivo models, we demonstrated a dual function of PDIA2 that enhances tumor-mediated pro-coagulation activity via tumor-derived extracellular vehicles (EVs). It also stimulates PCa cell proliferation, colony formation, and xenograft growth androgen-independently. Mechanistically, PDIA2 activates the tissue factor (TF) on EVs through its isomerase activity, which subsequently triggers a pro-thrombotic cascade in the blood. Additionally, TF-containing EVs can activate the Src kinase inside PCa cells to enhance the AR signaling ligand independently. Androgen deprivation does not alter PDIA2 expression in PCa cells but enhances PDIA2 translocation to the cell membrane and EVs via suppressing the clathrin-dependent endocytic process. Co-recruitment of AR and FOXA1 to the PDIA2 promoter is required for PDIA2 transcription under androgen-deprived conditions. Importantly, blocking PDIA2 isomerase activity suppresses the pro-coagulation activity of patient plasma, PCa cell, and xenograft samples as well as castrate-resistant PCa xenograft growth. These results demonstrate that PDIA2 promotes VTE and tumor progression via activating TF from tumor-derived EVs. They rationalize pharmacological inhibition of PDIA2 to suppress ADT-induced VTE and castrate-resistant tumor progression.


Assuntos
Progressão da Doença , Neoplasias de Próstata Resistentes à Castração , Isomerases de Dissulfetos de Proteínas , Trombose Venosa , Animais , Humanos , Masculino , Camundongos , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/efeitos adversos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Isomerases de Dissulfetos de Proteínas/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Tromboplastina/metabolismo , Tromboplastina/genética , Trombose Venosa/metabolismo , Trombose Venosa/induzido quimicamente , Trombose Venosa/patologia , Trombose Venosa/genética , Trombose Venosa/etiologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Chemosphere ; 355: 141661, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521103

RESUMO

The accumulation of lead (Pb) in soil resulted from industrialization and urbanization poses a threat to human health and the ecosystem. This study proposes a mathematical model for Pb migration and transformation in soil porous media, aiming to guide the design of electrokinetic remediation schemes for Pb-contaminated soils. To improve the validity of the model, the chemical reactions considered in the model are all based on chemical reaction kinetics, which were usually overlooked for model simplification. The model quantitatively describes various physical and chemical processes of Pb at the soil-pore fluid interface and in the pore fluid, including diffusion, electromigration, electroosmosis, electrolytic water reaction, precipitation, adsorption/desorption, protonation/deprotonation reaction, and water self-ionization reaction. The numerical results show that the pH value is a key factor affecting the distribution of Pb in the soil and determining the removal efficiency of Pb. The effects of different enhancement methods on Pb concentration distribution and removal efficiency were evaluated with this model. It was found that placing a cation exchange membrane at the cathode boundary while using 0.01 M nitric acid as anode electrolyte can effectively improve Pb removal efficiency from 3.9% to 93.6%. The developed model can be used to guide the design of the enhanced electrokinetic remediation schemes.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Humanos , Chumbo , Ecossistema , Cinética , Solo , Água
14.
IEEE Trans Vis Comput Graph ; 30(5): 2496-2506, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38498759

RESUMO

Nowadays, AR HMDs are widely used in scenarios such as intelligent manufacturing and digital factories. In a factory environment, fast and accurate text input is crucial for operators' efficiency and task completion quality. However, the traditional AR keyboard may not meet this requirement, and the noisy environment is unsuitable for voice input. In this article, we introduce Eye-Hand Typing, an intelligent AR keyboard. We leverage the speed advantage of eye gaze and use a Bayesian process based on the information of gaze points to infer users' text input intentions. We improve the underlying keyboard algorithm without changing user input habits, thereby improving factory users' text input speed and accuracy. In real-time applications, when the user's gaze point is on the keyboard, the Bayesian process can predict the most likely characters, vocabulary, or commands that the user will input based on the position and duration of the gaze point and input history. The system can enlarge and highlight recommended text input options based on the predicted results, thereby improving user input efficiency. A user study showed that compared with the current HoloLens 2 system keyboard, Eye-Hand Typing could reduce input error rates by 28.31 % and improve text input speed by 14.5%. It also outperformed a gaze-only technique, being 43.05% more accurate and 39.55% faster. And it was no significant compromise in eye fatigue. Users also showed positive preferences.


Assuntos
Fixação Ocular , Interface Usuário-Computador , Teorema de Bayes , Gráficos por Computador , Mãos
15.
Front Cell Dev Biol ; 12: 1362671, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425500

RESUMO

Producing an adequate number of muscle stem cells (MuSCs) with robust regenerative potential is essential for the successful cell therapy of muscle-wasting disorders. We have recently developed a method to produce skeletal myogenic cells with exceptional engraftability and expandability through an in vivo pluripotent stem cell (PSC) differentiation approach. We have subsequently mapped engraftment and gene expression and found that leukemia inhibitory factor receptor (Lifr) expression is positively correlated with engraftability. We therefore investigated the effect of LIF, the endogenous ligand of LIFR, on cultured MuSCs and examined their engraftment potential. We found that LIF-treated MuSCs exhibited elevated expression of PAX7, formed larger colonies from single cells, and favored the retention of PAX7+ "reserve cells" upon myogenic differentiation. This suggested that LIF promoted the maintenance of cultured MuSCs at a stem cell stage. Moreover, LIF enhanced the engraftment capability of MuSCs that had been expanded in vitro for 12 days by 5-fold and increased the number of MuSCs that repopulated the stem cell pool post-transplantation. These results thereby demonstrated the effectiveness of our in vivo PSC differentiation platform to identify positive regulators of the engraftability of cultured MuSCs.

16.
Oncol Rep ; 51(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456515

RESUMO

After the publication of the article, an interested reader drew to the authors' attention that, in the western blots shown in Fig. 5C and D, a pair of data panels were inadvertently duplicated comparing between panels (C) and (D); in addition, the cell migration data shown in Fig. 7F on p. 1852 were selected incorrectly. The authors have examined their original data, and realize that these errors arose inadvertently as a consequence of their mishandling of their data. The revised versions of Figs. 5 and 7, featuring the corrected data for the caspase-8 experiment in Fig. 5C and alternative data for the cell migration assay experiments in Fig. 7F, are shown on the next two pages. The revised data shown for these Figures do not affect the overall conclusions reported in the paper. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. Furthermore, the authors apologize to the readership for any inconvenience caused. [Oncology Reports 40: 1843-1854, 2018; DOI: 10.3892/or.2018.6593].

17.
IEEE Trans Image Process ; 33: 2226-2237, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38470583

RESUMO

Cross-modal retrieval (e.g., query a given image to obtain a semantically similar sentence, and vice versa) is an important but challenging task, as the heterogeneous gap and inconsistent distributions exist between different modalities. The dominant approaches struggle to bridge the heterogeneity by capturing the common representations among heterogeneous data in a constructed subspace which can reflect the semantic closeness. However, insufficient consideration is taken into the fact that learned latent representations are actually heavily entangled with those semantic-unrelated features, which obviously further compounds the challenges of cross-modal retrieval. To alleviate the difficulty, this work makes an assumption that the data are jointly characterized by two independent features: semantic-shared and semantic-unrelated representations. The former presents characteristics of consistent semantics shared by different modalities, while the latter reflects the characteristics with respect to the modality yet unrelated to semantics, such as background, illumination, and other low-level information. Therefore, this paper aims to disentangle the shared semantics from the entangled features, andthus the purer semantic representation can promote the closeness of paired data. Specifically, this paper designs a novel Semantics Disentangling approach for Cross-Modal Retrieval (termed as SDCMR) to explicitly decouple the two different features based on variational auto-encoder. Next, the reconstruction is performed by exchanging shared semantics to ensure the learning of semantic consistency. Moreover, a dual adversarial mechanism is designed to disentangle the two independent features via a pushing-and-pulling strategy. Comprehensive experiments on four widely used datasets demonstrate the effectiveness and superiority of the proposed SDCMR method by achieving a new bar on performance when compared against 15 state-of-the-art methods.

18.
J Gene Med ; 26(2): e3673, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38404059

RESUMO

BACKGROUND: Breast cancer (BC), a malignant tumor, is a significant cause of death and disability among women globally. Recent research indicates that copy number variation plays a crucial role in tumor development. In this study, we employed the Single-Cell Variational Aneuploidy Analysis (SCEVAN) algorithm to differentiate between malignant and non-malignant cells, aiming to identify genetic signatures with prognostic relevance for predicting patient survival. METHODS: We analyzed gene expression profiles and associated clinical data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Using the SCEVAN algorithm, we distinguished malignant from non-malignant cells and investigated cellular interactions within the tumor microenvironment (TME). We categorized TCGA samples based on differentially expressed genes (DEGs) between these cell types. Subsequent Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted. Additionally, we developed polygenic models for the DEGs using least absolute shrinkage and selection operator-penalized Cox regression analysis. To assess the prognostic accuracy of these characteristics, we generated Kaplan-Meier and receiver operating characteristic curves from training and validation datasets. We also monitored the expression variations of prognostic genes across the pseudotime of malignant cells. Patients were divided into high-risk and low-risk groups based on median risk scores to compare their TME and identify potential therapeutic agents. Lastly, polymerase chain reaction was used to validate seven pivotal genes. RESULTS: The SCEVAN algorithm identified distinct malignant and non-malignant cells in GSE180286. Cellchat analysis revealed significantly increased cellular communication, particularly between fibroblasts, endothelial cells and malignant cells. The DEGs were predominantly involved in immune-related pathways. TCGA samples were classified into clusters A and B based on these genes. Cluster A, enriched in immune pathways, was associated with poorer prognosis, whereas cluster B, predominantly involved in circadian rhythm pathways, showed better outcomes. We constructed a 14-gene prognostic signature, validated in a 1:1 internal TCGA cohort and external GEO datasets (GSE42568 and GSE146558). Kaplan-Meier analysis confirmed the prognostic signature's accuracy (p < 0.001). Receiver operating characteristic curve analysis demonstrated the predictive reliability of these prognostic features. Single-cell pseudotime analysis with monocle2 highlighted the distinct expression trends of these genes in malignant cells, underscoring the intratumoral heterogeneity. Furthermore, we explored the differences in TME between high- and low-risk groups and identified 16 significantly correlated drugs. CONCLUSION: Our findings suggest that the 14-gene prognostic signature could serve as a novel biomarker for forecasting the prognosis of BC patients. Additionally, the immune cells and pathways in different risk groups indicate that immunotherapy may be a crucial component of treatment strategies for BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Prognóstico , Variações do Número de Cópias de DNA , Células Endoteliais , Reprodutibilidade dos Testes , RNA , Microambiente Tumoral/genética
19.
Commun Biol ; 7(1): 215, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383737

RESUMO

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.


Assuntos
Adenina , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Adenina/análogos & derivados , Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Antígeno CD47/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Pulmonares/patologia , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fagocitose , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
20.
Aging (Albany NY) ; 16(4): 4014-4032, 2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38393698

RESUMO

BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Citofagocitose , Prognóstico , Anticorpos , Nomogramas , Microambiente Tumoral
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