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1.
Toxicol In Vitro ; 98: 105827, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657712

RESUMO

Recent times have witnessed an increase in both incidence and mortality rates of prostate cancer. While some individuals with localized or metastatic cancer may progress slowly with a lower mortality risk, those with intermediate or high-risk cancer often face a higher likelihood of death, despite treatment. Bisphenol A (BPA) has been linked to various cancers, including prostate and breast cancer, yet the relationship between bisphenol S (BPS) and human health remains underexplored. In our study, we employed ssGSEA analysis to evaluate the BPS-associated score in a prostate cancer cohort. Additionally, differential expression analysis identified BPS-related genes within the same group. Through COX and LASSO regression analyses, we developed and validated a BPS-related risk model using ROC curve and survival analyses. A nomogram, integrating clinical characteristics with this risk model, was established for improved predictive accuracy, further substantiated by calibration curve validation. Molecular docking analysis suggested potential binding between SDS and BPS. We also conducted cell proliferation assays on C4-2 and LNCaP prostate cancer cells, revealing increased cell growth at a BPS concentration of 10-7 M, as evidenced by CCK8 and EdU assays. In summary, our findings shed light on the BPS-prostate cancer linkage, identifying BPS-associated genes, establishing a validated risk model, exploring SDS-BPS binding potential, and assessing BPS's effect on prostate cancer cell growth. These insights underscore the need for further investigation into BPS and its impact on human diseases.

2.
J Transl Med ; 22(1): 5, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38169393

RESUMO

BACKGROUND: Bladder cancer is very common worldwide. PIGT is a subunit of the glycosylphosphatidylinositol transamidase which involves in tumorigenesis and invasiveness. m6A modification of mRNA has been linked to cell proliferation, tumor progression and other biological events. However, how PIGT is regulated and what is the function of PIGT in bladder cancer remains to be elucidated. METHODS: PIGT was silenced or overexpressed to study its role in regulating bladder cancer. Cell proliferation and invasion were examined with the Cell Counting Kit-8, colony formation and Transwell assay, respectively. Cellular oxygen consumption rates or extracellular acidification rates were detected by a XF24 Analyzer. Quantitative RT-PCR and immunoblots were performed to detect mRNA and protein levels. RESULTS: PIGT was overexpressed in bladder cancer. Silencing PIGT inhibited cell proliferation, oxidative phosphorylation, and glycolysis. Overexpressing PIGT promoted cell proliferation, oxidative phosphorylation, glycolysis in vitro and tumor metastasis in vivo by activating glucose transporter 1 (GLUT1). PIGT also promoted GLUT1 glycosylation and membrane trafficking. Wilms' tumor 1-associated protein (WTAP) mediated PIGT m6A modification, and m6A reader, insulin-like growth factor 2 mRNA-binding protein (IGF2BP2), binds to the methylated PIGT to promote the stability of PIGT, leading to up-regulation of PIGT. CONCLUSION: WTAP mediates PIGT m6A modification to increase the stability of PIGT via the IGF2BP2, which enhances cell proliferation, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Linhagem Celular Tumoral , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glicosilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proliferação de Células/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Glicólise/genética , Proteínas de Ligação a RNA/metabolismo
3.
Eur J Med Res ; 28(1): 588, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38093375

RESUMO

Targeted therapy is pivotal in renal carcinoma treatment, and the dual-inhibitor NVP-BEZ235 has emerged as a promising candidate in preliminary studies. Its effectiveness against renal carcinoma and the mechanisms underlying potential resistance, however, warrant further exploration. This study aims to elucidate these aspects, enhancing our understanding of NVP-BEZ235's future clinical utility. To investigate resistance mechanisms, renal cancer cell lines were exposed to progressively increasing concentrations of NVP-BEZ235, leading to the development of stable resistance. These resistant cells underwent extensive RNA-sequencing analysis. We implemented gene interference techniques using plasmid vectors and lentivirus and conducted regular IC50 assessments. To pinpoint the role of LncRNAs, we utilized FISH and immunofluorescence staining assays, supplemented by RNA pull-down and RIP assays to delineate interactions between LncRNA and its RNA-binding protein (RBP). Further, Western blotting and qRT-PCR were employed to examine alterations in signaling pathways, with an animal model providing additional validation. Our results show a marked increase in the IC50 of NVP-BEZ235 in resistant cell lines compared to their parental counterparts. A significant revelation was the role of LncRNA-CHKB-AS1 in mediating drug resistance. We observed dysregulated expression of CHKB-AS1 in both clinical samples of clear cell renal cell carcinoma (ccRCC) and cell lines. In vivo experiments further substantiated our findings, showing that CHKB-AS1 overexpression significantly enhanced tumor growth and resistance to NVP-BEZ235 in a subcutaneous tumorigenesis model, as evidenced by increased tumor volume and weight, whereas CHKB-AS1 knockdown led to a marked reduction in these parameters. Critically, CHKB-AS1 was identified to interact with MAP4, a key regulator in the phosphorylation of the PI3k/Akt/mTOR pathway. This interaction contributes to a diminished antitumor effect of NVP-BEZ235, highlighting the intricate mechanism through which CHKB-AS1 modulates drug resistance pathways, potentially impacting therapeutic strategies against renal carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Animais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Serina-Treonina Quinases TOR/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proliferação de Células , Proteínas Associadas aos Microtúbulos , Linhagem Celular Tumoral
4.
Eur J Med Res ; 28(1): 487, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932808

RESUMO

Tanshinone IIA is a lipophilic organic compound from the root of Danshen (Salvia miltiorrhiza) and is one of the most well-known Tanshinone molecules by pharmacologists. In recent years, in addition to effects of anti-cardiovascular and neurological diseases, Tanshinone IIA has also shown some degrees of anti-prostate cancer potential. Although they do have some studies focusing on the molecular mechanism of Tanshinone IIA's anti-prostate cancer effects, a further understanding on the transcriptomic and structural level is still lacking. In this study, transcriptomic sequencing technology and computer technology were employed to illustrate the effects of Tanshinone IIA on prostate cancer through bioinformatic analysis and molecular dynamics simulation, and PPARG was considered to be one of the targets for Tanshinone IIA according to docking scoring and dynamic calculation. Our study provides a novel direction to further understand the mechanism of the effects of Tanshinone IIA on prostate cancer, and further molecular biological studies need to be carried on to further investigate the molecular mechanism of Tanshinone IIA's anti-prostate cancer effect through PPARG.


Assuntos
PPAR gama , Neoplasias da Próstata , Humanos , Masculino , Simulação de Acoplamento Molecular , Transcriptoma
5.
Front Oncol ; 13: 1256720, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849802

RESUMO

The aim of our research is to explore the various characteristics and genetic profiles of clear cell renal cell carcinoma (ccRCC) in order to discover possible predictors of prognosis and targets for treatment. By utilizing ssGSEA scores, we categorized patients with ccRCC into groups based on their phenotype, distinguishing between low and high. This categorization revealed significant variations in the expression of crucial immune checkpoint genes and Human Leukocyte Antigen (HLA) genes, suggesting the presence of a potential immune evasion tactic in different subtypes of ccRCC. A predictive model was built using genes that are expressed differently and linked to cell death, showing strong effectiveness in categorizing patient risk. Furthermore, we discovered a noteworthy correlation among risk scores, infiltration of immune cells, the expression of genes related to immune checkpoint inhibitors, and diverse clinical features. This indicates that our scoring system for risk could function as a comprehensive gauge of the severity of the disease. The examination of the mutational terrain further highlighted the predominance of particular genetic changes, including VHL and PBRM1 missense mutations. Finally, we have discovered the function of DKK1 in facilitating cell death in ccRCC, presenting an additional possibility for therapeutic intervention. The results of our study suggest the possibility of incorporating molecular information into clinical prediction, which could lead to personalized treatment approaches in ccRCC.

6.
Prev Med Rep ; 36: 102464, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37854665

RESUMO

The coronavirus disease 2019 (COVID-19) may have a negative impact on the sexual health of male adults. An online questionnaire survey was conducted among male adults from February 04, 2023 to March 15, 2023 to analyze the impact of COVID-19 on the sexual health of male adults in China. Participants provided about their medical, social, lifestyle, and family situations information through questionnaires including the Brief Sexual Function Inventory (BSFI). Sexual function problems were defined based on predetermined cutoff values of the BSFI domain scores. A total of 1,250 male adults were included with median age as 32 years. According to the analysis of statistical results, sexual drive and erections firm enough to have sexual intercourse were reported to be present only a few days or less last month among 14.8 % and 11.1 % of COVID-19 survivors, respectively. Compared with uninfected persons, COVID-19 survivors had significantly lower scores on all BSFI domains and an increased risk of problems with sexual drive and erectile. In multivariate models of COVID-19 survivors, age ≥30 years, rural resident, lower education level, manual worker, lower income, and shorter duration from recovery to survey date were significantly associated with poorer overall sexual function. In this study, COVID-19 survivors was reported to have significantly poorer sexual function than uninfected persons. The COVID-19 may have had a significant impact on the sexual health of Chinese male adults. We need to focus on sexual dysfunction in COVID-19 survivors, and proactively provide effective interventions.

7.
Pharmacol Res ; 197: 106940, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37758102

RESUMO

Small nucleolar RNA host gene 15 (SNHG15) plays an oncogenic role in many cancers. However, the role of SNHG15 in bladder cancer (BLCA) remains unclear. In this study, the regulation of SNHG15 on the activities of BLCA cells (T24 and RT112) was investigated. In detail, super-enhancers (SEs), differentially expressed genes, and functional enrichment were detected by bioinformatic analyses. Mutant cell lines lacking SNHG15-SEs were established using CRISPR-Cas9. Relative gene expression was detected by quantitative polymerase chain reaction (qPCR), western blot, in situ hybridization, and immunohistochemistry assays. Cell senescence, apoptosis, viability, and proliferation were measured. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter gene assays were conducted to analyze the interactions between genes. A novel super-enhancer of SNHG15 (SNHG15-SEs) was discovered in several BLCA datasets. The deletion of SNHG15-SEs resulted in a significant downregulation of SNHG15. Mechanistically, the core active region of SNHG15-SEs recruited the transcription factor FOSL1 to facilitate the SNHG15 transcription, thereby inducing the proliferation and metastasis of BLCA cells. Deletion of SNHG15-SEs inhibited the growth and metastasis of T24 and RT112 cells by inactivating the WNT/CTNNB1 pathway activation. Overexpression of FOSL1 in SNHG15-SEs restored the cell proliferation and metastasis. Next, a xenograft mouse model showed that SNHG15-SEs deletion inhibited the proliferation and metastasis of BLCA cells in vivo. Collectively, our data indicate that SNHG15-SEs recruit FOSL1 to promote the expression of SNHG15 which interacts with CTNNB1 in the nucleus to activate the transcription of ADAM12, leading to the malignance of BLCA cells.


Assuntos
Neoplasias da Bexiga Urinária , Via de Sinalização Wnt , Humanos , Animais , Camundongos , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária , Células Epiteliais , Apoptose
8.
Quant Imaging Med Surg ; 13(9): 6129-6138, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37711828

RESUMO

Background: Reproducing the native patellar ridge high point while maximizing osseous coverage is important for the success of patellar replacement, but it cannot always be achieved simultaneously. This study aimed to thoroughly investigate the relationships and their influencing factors between the positions of the high point of patellar ridge (HPPR) and the morphology of the patellar resected surface. Methods: Four hundred seventy-three patients (265 men, 208 women) aged 18 to 50 years with knee injuries before arthroscopy were retrospectively collected for this cross-sectional study. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to construct 3D computer models of the patella and patellar cartilage. The morphometric characteristics of the patellar cut after virtual resection and the HPPR position relative to the patellar cut centre were measured and analyzed. Results: The medial displacements of the HPPR were positively correlated with Wiberg's classification and index (all P<0.001). The mean values of HPPR's medial displacements were 0.15 of the medial width of patellar cut, and 93.2% of all patella ranged from 0 to 0.3. When the implant's apex were placed at 0.15 of the medial width of patellar cut medialized, the proportion of implant placement errors within 1 mm of the native high point was 12% more in female patella (P=0.01), and 7% more in all patella (P=0.03) than 3 mm medialized. Conclusions: Wiberg's system can roughly predicted the medial-lateral position of the HPPR. The HPPR was mainly medially located at the 0.15 of the medial patellar width approximately, and 15% medialized of the implant's apex can better reproduce the native patellar high point than 3 mm medialized. The current results provide basic data for patellar implant selection, preoperative planning, and implant design to reproduce the native patellar high point better while maximizing osseous coverage for patellar resurfacing.

9.
J Periodontal Res ; 58(6): 1235-1247, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37712743

RESUMO

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. METHODS: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs. CONCLUSION: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis.


Assuntos
Periodontite , RNA Longo não Codificante , Humanos , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteocalcina/metabolismo , Osteogênese , Ligamento Periodontal , Periodontite/metabolismo , Proteínas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células-Tronco/metabolismo , Fatores Estimuladores Upstream/metabolismo
10.
Curr Psychol ; : 1-11, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37359687

RESUMO

The present study proposes a moderated mediation model that examines how and when unethical pro-supervisor behavior is related to employees' family satisfaction. The two-wave study design consisted of 207 full-time employees in China. The study results indicate that unethical pro-supervisor behavior is negatively related to family satisfaction, and that workplace ostracism mediates the influence of unethical pro-supervisor behavior on family satisfaction. In addition, the relationship between workplace ostracism and family satisfaction as well as the indirect influence of unethical pro-supervisor behavior on family satisfaction through workplace ostracism, are moderated by employees' work-home segmentation preference. The study findings not only enrich the literature on unethical pro-supervisor behavior, but also have important practical implications for organizational managers.

11.
PeerJ Comput Sci ; 9: e1411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346629

RESUMO

At present, China is moving towards the direction of "Industry 4.0". The development of the automobile industry, especially intelligent automobiles, is in full swing, which brings great convenience to people's life and travel. However, at the same time, urban traffic pressure is also increasingly prominent, and the situation of traffic congestion and traffic safety is not optimistic. In this context, the Internet of Vehicles (also known as "IoV") opens up a new way to relieve urban traffic pressure. Therefore, in order to further optimize the road network traffic conditions in the IoV environment, this research focuses on the traffic flow prediction algorithm on the basis of deep learning to enhance traffic efficiency and safety. First, the study investigates the short-time traffic flow prediction by combining the characteristics of the IoV environment. To address the issues that existing algorithms cannot automatically extract data features and the model expression capability is weak, the study chooses to build a deep neural network using GRU model in deep learning for short-time traffic flow prediction, thereby improving the prediction accuracy of algorithm. Secondly, a fine-grained traffic flow statistics approach suitable for the IoV situation is suggested in accordance with the deep learning model that was built. The algorithm sends the vehicle characteristic data obtained through GRU model training into the fine-grained traffic flow statistics algorithm, so as to realize the statistics of traffic information of various types of vehicles. The advantage of this algorithm is that it can well count the traffic flow of multiple lanes, so as to better predict the current traffic status and achieve traffic optimization. Finally, the IoV environment is constructed to confirm the effectiveness of the prediction model. The prediction results prove that the new algorithm has good performance in traffic flow statistics in different scenarios.

12.
Front Oncol ; 13: 1136835, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937411

RESUMO

Globally, prostate cancer remains a leading cause of mortality and morbidity despite advances in treatment. Research on prostate cancer has primarily focused on the malignant epithelium, but the tumor microenvironment has recently been recognized as an important factor in the progression of prostate cancer. Cancer-associated fibroblasts (CAFs) play an important role in prostate cancer progression among multiple cell types in the tumor microenvironment. In order to develop new treatments and identify predictive and prognostic biomarkers for CAFs, further research is needed to understand the mechanism of action of prostate cancer and CAF. In this work, we performed the single-cell RNA sequence analysis to obtain the biomarkers for CAFs, and ten genes were finally regarded as the marker genes for CAFs. Based on the ssGSEA algorithm, the prostate cancer cohort was divided into low- and high-CAFs groups. Further analysis revealed that the CAFs-score is associated with many immune-related cells and immune-related pathways. In addition, between the low- and high-CAFs tissues, a total of 127 hub genes were discovered, which is specific in CAFs. After constructing the prognostic prediction model, SLPI, VSIG2, CENPF, SLC7A1, SMC4, and ITPR2 were finally regarded as the key genes in the prognosis of patients with prostate cancer. Each patient was assigned with the risk score as follows: SLPI* 0.000584811158157081 + VSIG2 * -0.01190627068889 + CENPF * -0.317826812875334 + SLC7A1 * -0.0410213995358753 + SMC4 * 0.202544454923637 + ITPR2 * -0.0824652047622673 + TOP2A * 0.140312081524807 + OR51E2 * -0.00136602095885459. The GSVA revealed the biological features of CAFs, many cancer-related pathways, such as the adipocytokine signaling pathway, ERBB signaling pathway, GnRH signaling pathway, insulin signaling pathway, mTOR signaling pathway and PPAR signaling pathway are closely associated with CAFs. As a result of these observations, similar transcriptomics may be involved in the transition from normal fibroblasts to CAFs in adjacent tissues. As one of the biomarkers for CAFs, CENPF can promote the proliferation ability of prostate cancer cells. The overexpress of CENPF could promote the proliferation ability of prostate cancer cells. In conclusion, we discuss the potential prognostic and therapeutic value of CAF-dependent pathways in prostate cancer.

13.
Brief Bioinform ; 24(3)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-36960769

RESUMO

Major histocompatibility complex (MHC) class II molecules play a pivotal role in antigen presentation and CD4+ T cell response. Accurate prediction of the immunogenicity of MHC class II-associated antigens is critical for vaccine design and cancer immunotherapies. However, current computational methods are limited by insufficient training data and algorithmic constraints, and the rules that govern which peptides are truly recognized by existing T cell receptors remain poorly understood. Here, we build a transfer learning-based, long short-term memory model named 'TLimmuno2' to predict whether epitope-MHC class II complex can elicit T cell response. Through leveraging binding affinity data, TLimmuno2 shows superior performance compared with existing models on independent validation datasets. TLimmuno2 can find real immunogenic neoantigen in real-world cancer immunotherapy data. The identification of significant MHC class II neoantigen-mediated immunoediting signal in the cancer genome atlas pan-cancer dataset further suggests the robustness of TLimmuno2 in identifying really immunogenic neoantigens that are undergoing negative selection during cancer evolution. Overall, TLimmuno2 is a powerful tool for the immunogenicity prediction of MHC class II presented epitopes and could promote the development of personalized immunotherapies.


Assuntos
Antígenos de Histocompatibilidade Classe II , Neoplasias , Humanos , Antígenos HLA , Apresentação de Antígeno , Aprendizado de Máquina
14.
Genet Res (Camb) ; 2023: 2355891, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741922

RESUMO

Chinese herbal medicine (CHM), which includes herbal slices and proprietary products, is widely used in China. Shenqi Dihuang (SQDH) is a traditional Chinese medicine (TCM) formula with ingredients that affect tumor growth. Despite recent advances in prognosis, patients with renal cell carcinoma (RCC) cannot currently receive curative treatment. The present study aimed to explore the potential target genes closely associated with SQDH. The gene expression data for SQDH and RCC were obtained from the TCMSP and TCGA databases. The SQDH-based prognostic prediction model reveals a strong correlation between RCC and SQDH. In addition, the immune cell infiltration analysis indicated that SQDH might be associated with the immune response of RCC patients. Based on this, we successfully built the prognostic prediction model using SQDH-related genes. The results demonstrated that CCND1 and NR3C2 are closely associated with the prognosis of RCC patients. Finally, the pathways enrichment analysis revealed that response to oxidative stress, cyclin binding, programmed cell death, and immune response are the most enriched pathways in CCND1. Furthermore, transcription regulator activity, regulation of cell population proliferation, and cyclin binding are closely associated with the NR3C2.


Assuntos
Carcinoma de Células Renais , Medicamentos de Ervas Chinesas , Neoplasias Renais , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Medicina Tradicional Chinesa , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo
15.
JCI Insight ; 8(1)2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36413416

RESUMO

Chronic inflammation is associated with lung tumorigenesis, in which NF-κB-mediated epigenetic regulation plays a critical role. Lung tumor suppressor G protein-coupled receptor, family C, member 5A (GPRC5A), is repressed in most non-small cell lung cancer (NSCLC); however, the mechanisms remain unclear. Here, we show that NF-κB acts as a transcriptional repressor in suppression of GPRC5A. NF-κB induced GPRC5A repression both in vitro and in vivo. Intriguingly, transactivation of NF-κB downstream targets was not required, but the transactivation domain of RelA/p65 was required for GPRC5A repression. NF-κB did not bind to any potential cis-element in the GPRC5A promoter. Instead, p65 was complexed with retinoic acid receptor α/ß (RARα/ß) and recruited to the RA response element site at the GPRC5A promoter, resulting in disrupted RNA polymerase II complexing and suppressed transcription. Notably, phosphorylation on serine 276 of p65 was required for interaction with RARα/ß and repression of GPRC5A. Moreover, NF-κB-mediated epigenetic repression was through suppression of acetylated histone H3K9 (H3K9ac), but not DNA methylation of the CpG islands, at the GPRC5A promoter. Consistently, a histone deacetylase inhibitor, but not DNA methylation inhibitor, restored GPRC5A expression in NSCLC cells. Thus, NF-κB induces transcriptional repression of GPRC5A via a complex with RARα/ß and mediates epigenetic repression via suppression of H3K9ac.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , NF-kappa B/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Ativação Transcricional , Epigênese Genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Células Epiteliais/metabolismo
16.
Front Immunol ; 13: 1037808, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405755

RESUMO

Renal cell carcinoma (RCC) is one of the leading causes of death in men. Messenger ribonucleic acid (mRNA) vaccines may be an attractive means to achieve satisfactory results. Cancer immunotherapy is a promising cancer treatment strategy. However, immunotherapy is not widely used in renal cell carcinoma, as only a few patients show a positive response. The present study aimed to identify potential antigens associated with renal cell carcinoma to develop an anti-renal cell carcinoma mRNA vaccine. Moreover, the immune subtypes of renal cell carcinoma cells were determined. The Cancer Genome Atlas (TCGA) analysis revealed gene expression profiles and clinical information. Antigen-presenting cells infiltrated the immune system using Tumor Immune Estimation Resource (TIMER) tool (http://timer.cistrome.org/). GDSC (Genomics of Drug Sensitivity in Cancer) database were used to estimate drug sensitivity. The 13 immune-related genes discovery could be targets for immunotherapy in renal cell carcinoma patients, as they were associated with a better prognosis and a higher level of antigen-presenting cells. These immune subtypes have significant relationships with immunological checkpoints, immunogenic cell death regulators, and RCC prognostic variables. Furthermore, DBH-AS1 was identified as a potential antigen for developing an mRNA vaccine. The CCK8 assay demonstrated that the proliferative capacity of 786-O and Caki-1 cells overexpressing DBH-AS1 was higher than in the control group. In addition, transwell assay revealed that 786-O and Caki-1 cells overexpressing DBH-AS1 showed higher invasion capacity compared with control. This study provides a theoretical basis for the development of mRNA vaccines. Our findings suggest that DBH-AS1 could be potential antigens for developing RCC mRNA vaccines.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Carcinoma de Células Renais/patologia , Antígenos de Neoplasias/genética , Neoplasias Renais/patologia , Imunoterapia , Fatores Imunológicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vacinas de mRNA
17.
Front Surg ; 9: 941104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386533

RESUMO

Objective: The limitations of tissue retraction and the amount of surgical working space have a great impact on extraperitoneal single-port robotic-assisted radical prostatectomy (sp-RARP) with the multiport robotic surgical system. We used an extraperitoneal tissue retraction technique to achieve tissue exposure and working space expansion. This study evaluated the safety, feasibility, and efficacy of the extraperitoneal tissue retraction technique in extraperitoneal pure sp-RARP with the da Vinci Si surgical system. Methods: Data from 42 patients were analyzed retrospectively from December 2018 to February 2020. The extraperitoneal tissue retraction technique was not used in 20 patients (group I) and was used in 22 patients (group II). Preoperative, intraoperative, and postoperative data were collected. The oncological and functional data during late follow-up were recorded. Results: All patients successfully underwent extraperitoneal pure sp-RARP. No patients required conversion to a multiport surgery or placement of additional assistant ports. The two groups were similar regarding baseline features. The median operation time in group I was significantly longer than that in group II (P < 0.001). The estimated blood loss volume in group I was significantly higher than that in group II (P < 0.001). There were no serious complications in either group. There were four cases of peritoneal tears in group I and none in group II (P = 0.043). The surgical margin and lymph nodes were negative in both groups. The oncological and functional outcomes were similar between the two groups 6 months after the procedure. Conclusions: The extraperitoneal tissue retraction technique is safe and feasible. The technique promotes tissue exposure and expands the surgical working space, which is important for achieving extraperitoneal pure sp-RARP with the da Vinci Si surgical system, especially for beginners. The short-term oncological and functional outcomes were within acceptable ranges. The long-term effects of this technique need further evaluation.

18.
Orthop Surg ; 14(9): 2210-2218, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35979987

RESUMO

OBJECTIVE: The bone mass around the prosthesis plays an important role in the stability of the prosthesis. This study aimed to assess the effect of postoperative activity on bone mineral density (BMD) in the proximal tibia 5 years after total knee arthroplasty (TKA). To provide a scientific guidance for postoperative functional exercise. METHODS: 110 patients underwent unilateral primary TKA were divided into three groups based on the University of California Los Angeles (UCLA) activity scale: low activity group (LA group, UCLA = 4, 5); medium activity group (MA group, UCLA = 6, 7); and high activity group (HA group, UCLA = 8, 9). The primary observation was a comparison of the BMD and BMD change percentage (ΔBMD (%)) in the periprosthetic tibia among the LA, MA and HA groups at 1 year, 3 years and 5 years. The secondary observations were radiographic evaluation (prosthetic stability, periprosthetic fractures, aseptic loosening and periprosthetic joint infection) and clinical evaluation (Knee Society Score (KSS), visual analogue score scores and range of motion (ROM)). A one-way ANOVA was used to compare the clinical scores and BMD among the three groups. RESULTS: The BMD of medial region decreased by 10.80%, 12.64%, 13.61% at 1, 3, and 5 years respectively; these were 5.72%, 6.26%, 7.83% in lateral region and 1.42%, 1.78%, 3.28% in diaphyseal region. For medial metaphyseal region, the BMD of the MA group was significantly greater than that of the LA and HA groups at 1 and 3 years (108.9 ± 5.2 vs. 106.1 ± 6.69 vs. 105.4 ± 5.2 and 108.5 ± 6.0 vs. 101.2 ± 6.76 vs. 103.0 ± 6.8, P < 0.01 and P < 0.001), and the BMD changes (ΔBMD (%)) in the MA group were significantly smaller than those in the LA and HA groups (8.75 ± 5.36 vs. 11.92 ± 5.49 vs. 12.70 ± 5.21 and 9.11 ± 5.11 vs. 16.04 ± 4.79 vs. 14.82 ± 4.26, P < 0.01 and P < 0.001). Regarding secondary observations, all of the prostheses were assessed as stable, without periprosthetic fractures, aseptic loosening and periprosthetic joint infection. Regarding KSS scores, there was no significant difference among the three groups. However, the VAS and ROM of the HA group were better than those of the MA and LA groups (1.65 ± 0.79 vs. 2.63 ± 0.77 vs. 3.00 ± 1.17, p < 0.001, and 111.90 ± 9.17 vs. 110.20 ± 6.78 vs. 102.90 ± 8.48, P < 0.001). CONCLUSION: Medium activity prevented periprosthetic bone loss in the medial metaphyseal region of the tibia after posterior-stabilized TKA, and moderate-intensity exercise is recommended for patients after TKA to reduce periprosthetic bone loss.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Fraturas Periprotéticas , Infecções Relacionadas à Prótese , Densidade Óssea , Seguimentos , Humanos , Articulação do Joelho , Osteoartrite do Joelho/cirurgia , Fraturas Periprotéticas/prevenção & controle , Fraturas Periprotéticas/cirurgia , Infecções Relacionadas à Prótese/cirurgia , Tíbia/cirurgia
19.
J Orthop Traumatol ; 23(1): 38, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35972661

RESUMO

OBJECTIVE: Increased femoral anteversion (FA) has been correlated with less varus deformities in osteoarthritic (OA) knees, but the relationship between FA and the degree of valgus deformity in osteoarthritic (OA) knees is still largely unknown. We aimed to thoroughly analyze the distribution of FA in relation to varus or valgus deformities of the lower extremity in OA knees, and to further clarify the relationship between FA and trochlear morphology. METHODS: 235 lower extremities with OA knees were divided into five groups according to the mechanical tibiofemoral angle: excessive valgus (< - 10°), moderate valgus (- 10° to - 3°), neutral (- 3° to 3°), moderate varus (3° to 10°), and excessive varus (> 10°). FA (measured using the posterior condylar axis [pFA] and the transepicondylar axis [tFA]) was measured, and the relationships of FA to the mechanical tibiofemoral angle and femoral trochlear morphology were identified. RESULTS: Excessive FA (pFA ≥ 20°) was observed in 30.2% of all patients and in 58.8% of patients in the excessive valgus group. pFA showed a strong correlation with mechanical tibiofemoral angle (p = 0.018). Both the pFA and the tFA of patients in the excessive valgus group were greater than those in other four groups (all p ≤ 0.037). There were significant correlations between tFA and trochlear parameters, including the sulcus angle (SA), lateral trochlear slope (LTS), and medial trochlear slope (MTS) (all p ≤ 0.028). CONCLUSION: High FA is prevalent, particularly in severe valgus knees, and FA is significantly related to the femoral trochlear morphology in OA knees. With the aim of improving the patellofemoral prognosis and complications, high FA should be considered during total knee arthroplasty.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Fêmur/anatomia & histologia , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Extremidade Inferior/cirurgia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia
20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(7): 853-859, 2022 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-35848182

RESUMO

Objective: To measure the position of patellar high point and the shape of the osteotomy surface, and to analyze their relationship, distribution, and gender differences. Methods: A total of 127 patients who needed anterior cruciate ligament reconstruction or meniscus repair due to trauma between September 2020 and September 2021 were selected as the research subjects. There were 71 males and 56 females, with an average age of 30.5 years (range, 19-43 years). There were significant differences in height and body weight between male and female patients ( P<0.05), but no significant difference in age and body mass index ( P>0.05). The three-dimensional model of the patella was reconstructed in Mimics software based on the CT images of the knee joint, and then imported into Geomagic Studio software for virtual osteotomy of the patella. The horizontal axis and vertical axis of the osteotomy surface represented the total width (W) and total height (H) of the osteotomy surface, respectively. Then the osteotomy surface was divided into four quadrants with the two axes: inner proximal, inner distal, outer proximal, and outer distal, and the inner width (W1), proximal height (H1), outer width (W2), and distal height (H2) were measured. The midpoint of the patellar ridge was selected as the patellar high point, and the point projected onto the osteotomy surface was defined as the optimal point for patellar prosthesis positioning (OPPP). The distances of OPPP on the horizontal axis (L1) and vertical axis (L2) relative to the center of the osteotomy surface were measured and L1/W1 and L2/H1 were also calculated; the quadrant distribution of OPPP was recorded. The patients were grouped according to gender, and the morphological parameters of the osteotomy surface (W, W1, W2, H, H1, H2) and the parameters related to the position of the OPPP (L1, L2, L1/W1, L2/H1) were analyzed between groups. Results: The width and height of each osteotomy surface of the patella in males were significantly larger than those in females ( P<0.05). As for the relationship between OPPP and osteotomy surface, the L1 of both male and female patients was 1-7 mm, and there was no significant difference in the distribution between the two groups ( χ 2=8.068, P=0.149); L1/W1 in both male and female patients was mainly 1/10-3/10. The L2 of male patients was 0-5 mm, and that of female patients was -1-4 mm; the difference in distribution between the two groups was significant ( χ 2=15.500, P=0.006); L2/H1 in both male and female patients was mainly 0-1/5. The OPPP of male patients was mainly distributed in the inner proximal (98.59%) and outer proximal (1.41%) quadrants, while the female patients were distributed in the inner proximal (91.07%), inner distal (7.14%), and outer proximal (1.79%) quadrants. There was significant difference in the OPPP quadrant distribution between the two groups ( χ 2=5.186, P=0.036). Conclusion: The OPPP points are widely distributed but mainly concentrated on around 1/5 of the medial patella surface and around 1/10 of the superior patella surface. A small portion of females' OPPP were inferior while all males' OPPP were superior to the center of the patella.


Assuntos
Artroplastia do Joelho , Patela , Adulto , Artroplastia do Joelho/métodos , China , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Osteotomia/métodos , Patela/diagnóstico por imagem , Patela/cirurgia , Tíbia/cirurgia
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