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Spinal cord injury (SCI) is a severe disabling disease that is characterized by inflammation and oxidative reactions. Tangeretin has been shown to possess significant antioxidant and anti-inflammatory activities. The Keap1/Nrf2 pathway, downstream of the Sesn2 gene, is involved in regulating the inflammation and oxidative response. The main objective of this study was to investigate the effect of tangeretin on SCI and its possible mechanism through cell and animal models. A T9 clamp injury was used for the mouse model and the LPS-induced stimulation of BV-2 cells was used for the cell model. The improvement of motor function after SCI was assessed by open field, swimming, and footprint experiments. The morphological characteristics of mouse spinal cord tissue and the levels of INOS, Sesn2, TNF-α, Keap1, Nrf2, IL-10, and reactive oxygen species (ROS) in vivo and in vitro were measured by several methods including western blotting, qPCR, immunofluorescence, HE, and Nissl staining. In vivo data showed that tangeretin can improve motor function recovery and reduce neuron loss and injury size in mice with SCI. Simultaneously, the in vitro findings suggested that treatment of BV-2 cells with tangeretin after LPS stimulation reduced the production of inflammatory factors and ROS, and could convert BV-2 cells from the M1 to the M2 type. Furthermore, Sesn2 knockout suppressed Keap1/Nrf2, inflammatory factors, ROS levels, and the M1 to M2 transition. Tangeretin can alleviate the inflammation and oxidative response induced by SCI by activating the Sesn2/Keap1/Nrf2 pathway.
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Disruption of the blood-spinal cord barrier (BSCB) is a critical event in the secondary injury following spinal cord injury (SCI). Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics. However, the specific involvement of Mertk in BSCB remains elusive. Here, we demonstrated a distinct role of Mertk in the repair of BSCB. Mertk expression is decreased in endothelial cells following SCI. Overexpression of Mertk upregulated tight junction proteins (TJs), reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis. Ultimately, this led to enhanced neural regeneration and functional recovery. Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk. These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.
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Vaccination-route-dependent adjuvanticity was identified as being associated with the specific features of antigen-carrying nanoparticles (NPs) in the present work. Here, we demonstrated that the mechanical properties and the decomposability of NP adjuvants play key roles in determining the antigen accessibility and thus the overall vaccine efficacy in the immune system when different vaccination routes were employed. We showed that soft nano-vaccines were associated with more efficient antigen uptake when administering subcutaneous (S.C.) vaccination, while the slow decomposition of hard nano-vaccines promoted antigen uptake when intravenous (I.V.) vaccination was employed. In comparison to the clinically used aluminum (Alum) adjuvant, the NP adjuvants were found to stimulate both humoral and cellular immune responses efficiently, irrespective of the vaccination route. For vaccination via S.C. and I.V. alike, the NP-based vaccines show excellent protection for mice from Staphylococcus aureus (S. aureus) infection, and their survival rates are 100% after lethal challenge, being much superior to the clinically used Alum adjuvant.
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INTRODUCTION: To gain an understanding of the changing faces of leadership in surgery, we examined trends in the demographics, additional degrees pursued, and scientific publication characteristics of the past presidents of three major surgery organizations. METHODS: We queried the BoardCertifiedDocs and Web of Science databases for the demographics, as well as the quantity and quality of publications, of the past presidents of the Association for Academic Surgery, Society of University Surgeons, and American College of Surgeons from 1970 to 2020. Data were analyzed by decade to identify any trends. RESULTS: We identified a total of 140 presidents from the organizations. The proportion of female presidents significantly increased from the 1990s to the 2010s (10% versus 33%, P < 0.05). The percentage of non-White presidents increased from the 1970s to the 2010s (3.33% versus 21.2%, P = 0.024). The percentage of presidents with additional degrees also increased from the 1970s to the 2010s (10.0% versus 48.8%, P = 0.039). During this same time period, the most common area of expertise of presidents shifted from cardiothoracic surgery to surgical oncology. The ratio of presidents' postinduction to preinduction publications was significantly increased among all three organizations in the 2010s compared to the 1970s (P < 0.05). Co-cluster analysis revealed a research topic change from the 1970s to the 2010s. CONCLUSIONS: The faces of surgical leadership have changed in terms of gender equality, racial diversity, surgical subspecialty, and additional degrees held. Such a transformation mirrors evolving diversity, equity, and inclusion initiatives, and it further highlights the adaptability of surgical leadership to the ever-changing landscape of surgery.
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Especialidades Quirúrgicas , Cirujanos , Humanos , Femenino , Sociedades Médicas , Liderazgo , PublicacionesRESUMEN
BACKGROUND AND OBJECTIVE: Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines. METHODS: A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus. RESULT: Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation. CONCLUSIONS: TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.
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Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Tacrolimus/uso terapéutico , Estudios Retrospectivos , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Human immunodeficiency virus type 1 (HIV-1) is the primary epidemic strain in China. Its genome contains two regulatory genes (tat and rev), three structural genes (gag, pol, and env), and four accessory genes (nef, vpr, vpu, and vif). Long terminal repeats (LTRs) in thegenome regulate integration, duplication, and expression of viral gene. The permissibility of HIV-1 infection hinges on the host cell cycle status. HIV-1 replicates by exploiting various cellular processes via upregulation or downregulation of specific cellular proteins that also control viral pathogenesis. For example, HIV-1 regulates the life cycle of p53, which in turn contributes significantly to HIV-1 pathogenesis. In this article, we review the interaction between HIV-1-associated factors and p53, providing information on their regulatory and molecular mechanisms, hinting possible directions for further research.
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Infecciones por VIH , VIH-1 , Humanos , VIH-1/genética , Proteína p53 Supresora de Tumor/genética , China , Genes ViralesRESUMEN
[This corrects the article DOI: 10.3389/fgene.2022.1090467.].
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The aim of this study was to evaluate the effects of replacing fish meal (FM) or soy protein concentrate (SPC) with wheat gluten on growth performance, feed utilization, and nutrient digestibility and retention in Japanese seabass (Lateolabrax japonicus). Seven isonitrogenous (441-456 g kg-1 crude protein) and isocaloric (21.5-22.0 MJ kg-1 gross energy) diets were produced to replace 0%, 33.3%, 66.7% and 100% of FM or SPC with a mixture of wheat gluten, wheat, and taurine (GWT, 77.5% wheat gluten, 20.5% wheat and 2.0% taurine). The gradual replacement of protein in FM with GWT had no significant effects on feed intake, whole-body composition, and the hepatosomatic and viscerosomatic indices, but resulted in a linear decrease in the weight gain rate, feed efficiency, and retention of nitrogen, energy, and essential amino acids (Arg, His, Ile, Leu, Lys, Met, Phe, Thr, and Val). The apparent digestibility of most essential amino acids (Cys, His, Leu, Lys, and Phe) and total amino acids increased linearly. Replacement protein in SPC with GWT had no significant effects on feed intake, growth, the feed conversion ratio, whole-body composition, and the hepatosomatic index, but resulted in a linear decrease in nitrogen, energy, and Met retention; the digestibility of Cys and Met increased linearly. Overall, wheat gluten is a more effective alternative for replacing protein in SPC than FM.
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Highly sensitive staphylococcal enterotoxin B (SEB) assay is of great importance for the prevention of toxic diseases caused by SEB. In this study, we present a gold nanoparticle (AuNP)-linked immunosorbent assay (ALISA) for detecting SEB in a sandwich format using a pair of SEB specific monoclonal antibodies (mAbs) performed in microplates. First, the detection mAb was labeled with AuNPs of different particle sizes (15, 40 and 60 nm). Then the sandwich immunosorbent assay for SEB detection was performed routinely in a microplate except for using AuNPs-labeled detection mAb. Next, the AuNPs adsorbed on the microplate were dissolved with aqua regia and the content of gold atoms was determined by graphite furnace atomic absorption spectrometry (GFAAS). Finally, a standard curve was drawn of the gold atomic content against the corresponding SEB concentration. The detection time of ALISA was about 2.5 h. AuNPs at 60 nm showed the highest sensitivity with an actual measured limit of detection (LOD) of 0.125 pg/mL and a dynamic range of 0.125-32 pg/mL. AuNPs at 40 nm had an actual measured LOD of 0.5 pg/mL and a dynamic range of 0.5 to 128 pg/mL. AuNPs at 15 nm had an actual measured LOD of 5 pg/mL, with a dynamic range of 5-1280 pg/mL. With detection mAb labeled with AuNPs at 60 nm, ALISA's intra- and interassay coefficient variations (CV) at three concentrations (2, 8, and 20 pg/mL) were all lower than 12% and the average recovery level was ranged from 92.7% to 95.0%, indicating a high precision and accuracy of the ALISA method. Moreover, the ALISA method could be successfully applied to the detection of various food, environmental, and biological samples. Therefore, the successful establishment of the ALISA method for SEB detection might provide a powerful tool for food hygiene supervision, environmental management, and anti-terrorism procedures and this method might achieve detection and high-throughput analysis automatically in the near future, even though GFAAS testing remains costly at present.
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Since the 1950s, hypoxia has been recognized as a crucial characteristic of cancer cells and their microenvironment. Indeed, hypoxia promotes the growth, survival, and metastasis of cancer cells. In the early 1990s, we found that as many phenomena in hypoxia can occur through hypoxia-inducible factor-1α (HIF1α). HIF1α is known as an angiogenesis converter in hypoxia, which promotes tumorigenesis, development, immune escape, recurrence, etc; This page goes into great detail on how HIF1α is activated during hypoxia and how the 2 signaling channels interact. It specifically emphasizes the significance of reactive oxygen species, the function of the PI3K/the serine/threonine kinase Akt/mammalian target of rapamycin cascade, and outlines the similarities between the 2 important factors (reactive oxygen species and PI3K/the serine/threonine kinase Akt/mammalian target of rapamycin cascade), nuclear factor κB, for HIF1α Important implications, in an effort to offer fresh views for the treatment of head and neck squamous cell carcinoma and HIF1α research.
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Neoplasias de Cabeza y Cuello , Proteínas Proto-Oncogénicas c-akt , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Especies Reactivas de Oxígeno , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteínas Serina-Treonina Quinasas , Hipoxia , Serina-Treonina Quinasas TOR , Fosfatidilinositol 3-Quinasas , Serina , Microambiente TumoralRESUMEN
Previous studies on solid organ transplantation have reported that a low time in therapeutic range (TTR) of tacrolimus increases the risk of poor outcomes. However, the reproducibility of the findings in liver transplantation has not yet been confirmed. The TTR, coefficient of variation (CV) and standard deviation (SD) were calculated for 207 adult liver transplant patients from the date of transplantation until the first episode of acute rejection (AR), graft loss, acute kidney injury (AKI), biliary complications, infection or the last follow-up. Kaplan-Meier curves, log-rank tests and Cox regression analyses were performed. Sixty-one (29.5%) patients reached the composite endpoint of AR, biliary complications and graft loss. The log-rank test indicated that the low TTR group had an increased risk of the composite endpoint (P < 0.001), AKI (P < 0.001) and infection (P < 0.001). Multivariate Cox regression analyses revealed that a 10% decrease in TTR was associated with an increased hazard for composite endpoint (hazard ratio [HR]: 1.185, P = 0.010), AKI (HR: 1.355, P < 0.001) and infection (HR: 1.357, P < 0.001). Unexpectedly, SD and CV demonstrated no association with the above-mentioned inferior outcomes. Compared with SD and CV, the TTR of tacrolimus was more correlated with inferior outcomes and may be a novel indicator for predicting the prognosis of liver transplantation.
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Lesión Renal Aguda , Trasplante de Riñón , Trasplante de Hígado , Adulto , Humanos , Tacrolimus/efectos adversos , Rechazo de Injerto/prevención & control , Trasplante de Hígado/efectos adversos , Supervivencia de Injerto , Reproducibilidad de los Resultados , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológicoRESUMEN
Nanoparticles have been identified in numerous studies as effective antigen delivery systems that enhance immune responses. However, it remains unclear whether this enhancement is a result of increased antigen uptake when carried by nanoparticles or the adjuvanticity of the nanoparticle carriers. Consequently, it is important to quantify antigen uptake by dendritic cells in a manner that is free from artifacts in order to analyze the immune response when antigens are carried by nanoparticles. In this study, we demonstrated several scenarios (antigens on nanoparticles or inside cells) that are likely to contribute to the generation of artifacts in conventional fluorescence-based quantification. Furthermore, we developed the necessary assay for accurate uptake quantification. PLGA NPs were selected as the model carrier system to deliver EsxB protein (a Staphylococcus aureus antigen) in order to testify to the feasibility of the established method. The results showed that for the same antigen uptake amount, the antigen delivered by PLGA nanoparticles could elicit 3.6 times IL-2 secretion (representative of cellular immune response activation) and 1.5 times IL-12 secretion (representative of DC maturation level) compared with pure antigen feeding. The findings above give direct evidence of the extra adjuvanticity of PLGA nanoparticles, except for their delivery functions. The developed methodology allows for the evaluation of immune cell responses on an antigen uptake basis, thus providing a better understanding of the origin of the adjuvanticity of nanoparticle carriers. Ultimately, this research provides general guidelines for the formulation of nano-vaccines.
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Objective This study is aimed to maximize the contrast of ultrasound imaging in limited nanometer size range, and enhance the accuracy of imaging by introducing specific targeting antibody. Methods A multiple scattering "FIG" nano contrast agent system was established by conventional nanobubble synthesis method. The structure of "FIG" nano contrast agent was composed of phospholipid as the bubble shell with self-decomposable nanoparticles loaded on the inner wall, and the specific antibody to glucose transporter 1 (GLUT-1) on the surface. Characterizations, in vitro and in vivo studies were employed to investigate the contrast and the accuracy of established nano bubble contrast agent. Results The in vitro imaging results revealed that with or without targeting ligand decoration, the "FIG" nano contrast agent system presented similar imaging enhancement, when compared with clinical used contrast imaging agent Sonovue. However, the imaging studies results in vivo showed that the "FIG" nano contrast agent system with targeting ligand decoration presented better imaging contrast and accuracy than free "FIG" nano contrast agent system, and both were better than Sonovue. Conclusion The antibody-targeted multiple scattering "FIG" nano contrast agents possesses the characteristics of high targeting and high enhancement resolution.
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Medios de Contraste , Hexafluoruro de Azufre , Medios de Contraste/química , Ligandos , AnticuerposRESUMEN
Background: Talaromycosis is an invasive endemic mycosis caused by the dimorphic fungus Talaromyces marneffei (T. marneffei, TM). It mainly affects immunodeficient patients, especially HIV-infected individuals, which causes significant morbidity and mortality. Culture-based diagnosis takes a long turnaround time with low sensitivity, leading to treatment delay. In this study, we aimed to evaluate the performance of Metagenomic Next-Generation Sequencing (mNGS) for the rapid diagnosis of talaromycosis in HIV-infected patients. Methods: Retrospectively analysis was conducted in HIV-infected cases at Changsha First Hospital (China) from January 2021 to March 2022. Patients who underwent routine microbiological examination and mNGS testing in parallel were enrolled. The clinical final diagnosis was used as a reference standard, and cases were classified into the TM group (60 cases) and the non-TM group (148 cases). The clinical performances of mNGS were compared with culture and serum Galactomannan (GM). The mixed infections detected by mNGS were analyzed. The impact of mNGS detection on treatment was also investigated. Results: The sensitivity of mNGS test reached 98.3% (95% CI, 89.8-99.9), which was significantly higher than culture (66.7% [95% CI, 53.2-77.9], P < 0.001) and serum GM (83.3% [95% CI, 71.0-91.2], P < 0.05). The specificity of 98.6% (95% CI, 94.7-99.7) was similar to culture (100.0% [95% CI, 96.8-100.0], P = 0.156), and superior to serum GM (91.9% [95% CI, 85.9-95.5], P < 0.05). In bronchoalveolar lavage fluid (BALF) samples, the positive rate of mNGS was 97.6%, which was significantly higher than culture (28.6%, P <0.001). mNGS has excellent performance in the identification of mixed infection in TM group patients. Cytomegalovirus, Epstein-Barr virus and Pneumocystis jirovecii were the most common concurrent pathogens. In summary, 60.0% (36/60) patients were added or adjusted to antimicrobial therapy after mNGS test. Conclusion: mNGS is a powerful technique with high specificity and sensitivity for the rapid diagnosis of talaromycosis. mNGS of BALF samples may be a good option for early identification of T. marneffei in HIV-infected individuals with manifestations of infection. Moreover, mNGS shows excellent performance in mixed infection, which benefits timely treatment and potential mortality reduction.
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Coinfección , Infecciones por Virus de Epstein-Barr , Infecciones por VIH , Humanos , Estudios Retrospectivos , Herpesvirus Humano 4 , Metagenómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Infecciones por VIH/complicaciones , Sensibilidad y EspecificidadRESUMEN
In the present study, the formation and structure of the inclusion compound of large-ring cyclodextrin and 4-terpineol were obtained through different experiments and molecular dynamics (MD) simulation. The analysis of FTIR, 1 H-NMR, and thermodynamic results confirmed the formation of clathrates. Analysis of molecular structure (root-mean-square deviation and radius of gyration), solubility, and interaction energy (Coul, H bond) based on MD simulations further clarified the nature of the clathrate and the conformational changes caused by guest molecules as well as inclusion complexes process trends. The inclusion complex reportedly has a new crystal structure with improved thermal stability. PRACTICAL APPLICATION: This is the first work to demonstrate the complex formation between 4-terpineol and large-ring cyclodextrin by molecular dynamics simulation. Molecular dynamics simulation confirmed the formation of inclusion complexes theoretically. Conformational changes of the molecules and the formation of complexes with improved thermal stability were observed. Complexing with large-ring cyclodextrin can be used as an effective means to encapsulate the aroma/flavor compounds.
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Ciclodextrinas , beta-Ciclodextrinas , Simulación de Dinámica Molecular , Ciclodextrinas/química , beta-Ciclodextrinas/química , Estructura Molecular , Termodinámica , SolubilidadRESUMEN
BACKGROUND: Despite the "fourth threat" of administrative demands, department chairs of surgery are expected to continue being a "triple threat": productive in research, outstanding in teaching, and exemplary in practice. Increased demands despite limited time are the catch-22 of promotion. This study investigated the influence of becoming department chair on scholarly vigor. METHODS: The surgeons listed in the Society of Surgical Chairs Membership Directory website (n = 118) were included in this study. Three measures were compared during the pre- and post-promotion phases: (1) research productivity (annual publications); (2) authorship position in publications (first-authorship, co-authorship, and senior-authorship); and (3) scholarly impact (m-index and National Institute of Health funding). RESULTS: The median [interquartile range] number of publications per year increased post-promotion versus pre-promotion (7.64 [3.81-14.15] vs 4.12 [2.08-7.03], P < .0005). The median [interquartile range] number of first-authorship publications per year decreased (0.50 [0.00-1.00] vs 0.64 [0.32-1.22], P < .05), whereas the median [interquartile range] number of co-authorship (4.23 [1.98-9.70] vs 2.02 [1.02-3.95], P < .0005) and senior-authorship (1.87 [0.99-4.03] vs 1.00 [0.36-2.24], P < .0005) publications per year increased post-promotion. The mean ± standard deviation m-index increased post-promotion (1.67 ± 1.19 vs 1.23 ± 0.83, P < .01). The mean ± standard deviation annual National Institute of Health grant funding amount of 48% (n = 57) of the department chairs increased post-promotion ($365,000 ± $899,000 vs $98,000 ± $143,000 pre-promotion, P < .05). CONCLUSION: The fourth threat of administrative demands is not a threat to the triple threat. This study showed the department chairs' continued scholarly vigor after promotion, providing insight into their tenacity, resilience, and dedication.
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Autoria , Cirujanos , Eficiencia , HumanosRESUMEN
Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.
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Neoplasias , Pueblo Asiatico/genética , Biomarcadores de Tumor/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Neoplasias/epidemiología , Neoplasias/genética , Neoplasias/terapia , Medicina de PrecisiónRESUMEN
A disintegrin and metalloprotease 12 (ADAM12), an essential transmembrane protein with metalloprotease, cell binding and intracellular signalregulating capabilities, has been reported to play a crucial role in various types of cancers. However, the biological function of ADAM12 in gastric cancer (GC) remains unclear. Bioinformatic and experimental analyses were used to determine the expression level and prognostic value of ADAM12 in GC. The level of DNA methylation and the competing endogenous RNA (ceRNA) network was identified using MethSurv, Starbase3.0, miRNet2.0 and experimental analyses. Then, the coexpression profiles of ADAM12 were determined and subjected to enrichment analysis using the LinkedOmics database. The proteinprotein interaction network and the docking model of ADAM12 were constructed using the GeneMANIA, STRING, and HDOCK webservers. The role of ADAM12 in tumor metastasis and immune infiltration was investigated using in vitro assays and TIMER database exploration. It was found that ADAM12 was overexpressed and was correlated with a poor prognosis of GC patients. In addition, the aberrant DNA methylation status and ceRNA regulation may contribute to the upregulation of ADAM12 in GC. Moreover, the enrichment analysis revealed that ADAM12 is involved in multiple vital biological functions and pathways, such as 'macrophage activation', 'extracellular matrix binding' and 'ECMreceptor interaction'. Subsequently, the proteinprotein interaction network and molecular docking model demonstrated that follistatin like 3 (FSTL3) is a potential binding partner of ADAM12. Finally, it was demonstrated that ADAM12 promotes tumor metastasis, immune infiltration and M2 macrophage polarization in GC. In summary, these results highlight the potential of ADAM12 to be used as a therapeutic target for GC.
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Proteína ADAM12/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas/genética , Línea Celular Tumoral , Humanos , Simulación del Acoplamiento Molecular , Pronóstico , Mapas de Interacción de Proteínas , Neoplasias Gástricas/patologíaRESUMEN
Background: Intervertebral disc degeneration (IDD) entails complex pathological changes and causes lower back pain (LBP). However, there is still a lack of understanding of the mechanisms involved in IDD, particularly regarding the roles of autophagy and ferroptosis. The current study used microarray data to investigate the pathogenesis of IDD and potential biomarkers related to autophagy and ferroptosis in IDD. Methods: Differentially expressed genes (DEGs) were identified by analyzing the mRNA and miRNA expression profiles of IDD patients from the Gene Expression Omnibus (GEO). The protein-protein interaction network, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were utilized. The Human Autophagy Database (HADb) and Ferroptosis Database were used in conjunction with hub genes to identify autophagy- and ferroptosis-related genes. The Transcription Factor -hub gene-miRNA network was constructed. Lastly, the expression of DEGs in normal and degenerated nucleus pulposus cells (NPCs) was investigated via the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: A total of 362 DEGs associated with IDD were identified. GO and KEGG analyses indicated that oxidative stress, extracellular matrix, PI3K-AKT signaling pathway, and ferroptosis were key factors in IDD occurrence. GSEA indicated that IDD was associated with changes in autophagy, iron ion homeostasis, extracellular matrix, and oxidative stress. Eighty-nine hub genes were obtained, including five that were autophagy-related and three that were ferroptosis-related. Of these, TP53 and SESN2 were the intersections of autophagy- and ferroptosis-related genes. In qRT-PCR analysis, CANX, SLC38A1, and TP53 were downregulated in degenerative NPCs, whereas GNAI3, SESN2, and VAMP3 were upregulated. Conclusion: The current study revealed aspects of autophagy- and ferroptosis-related genes involved in IDD pathogenesis, warranting further investigation.