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Isoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R-induced upregulation of miR-210, a hypoxia-responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR-210 in regulating the effects of isoflurane preconditioning on OGD/R-induced cardiomyocyte injury, AC16 cells were transfected with anti-miR-210 or control anti-miRNA. Results showed that isoflurane preconditioning attenuated OGD/R-induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK-MB levels), which could be reversed by anti-miR-210. Isoflurane preconditioning also prevented OGD/R-induced increase in apoptotic rate, caspase-3 and caspase-9 activities, and Bax level and decrease in Bcl-2 expression level, while anti-miR-210 blocked these effects. We also found that anti-miR-210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R-induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p-DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR-210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR-210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R-induced cardiac cytotoxicity by regulating the miR-210/BNIP3 axis.
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Previous published data have confirmed that the addition of a citric acid meal improves the accuracy of the 13C-urea breath test (13C-UBT). However, some studies have suggested that a citric acid test meal may not be necessary. Thus, the aim of this study was to evaluate the combination of a 13C-UBT with a citric acid meal for the diagnosis of Helicobacter pylori (Hp) infection in a Chinese population, particularly for patients with results in the gray zone. In this paired self-controlled study, all subjects had previously undergone 13C-UBTs without citric acid meals and were randomly divided into two groups based on different doses of citric acid (a low-dose citric acid group and a high-dose citric acid group, comprising meals with 0.68 g and 3.84 g citric acid powder, respectively). Positive rapid urease test (CLO) test and histology results were considered the 'gold standard'. The mean delta over baseline (DOB) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the two groups, particularly for patients with results in the gray zone. In total, 285 patients were tested. Of these patients, 189 were included in the low-dose citric acid group, and 96 were included in the high-dose citric acid group. Among patients with a positive 13C-UBT result without citric acid [delta over baseline (DOB) value ≥ 4, n = 174] and a negative 13C-UBT result without citric acid (DOB value < 4, n = 111), 8.0% (14/174) were false positive, and 0.9% (1/111) was false negative as determined by gold standard. Of 14 patients with false positive, 78.6% (11/14) false positive were in the gray zone of 4-10. However, there were no false positive 13C-UBT results with citric acid in the the gray zone of 4-10. In the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, NPV and accuracy at 15 min were as follows: 99.1% vs. 99.1%, 97.5% vs. 88.9%, 98.2% vs. 92.2%, 98.8% vs. 98.6% and 98.4% vs. 94.7%, respectively. In the the gray zone of 4.0-10.0, the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, and accuracy at 15 min were as follows: 94.4% vs. 100.0%, 100.0% vs. 0%, 100.0% vs. 75.0% and 95.8% vs. 75.0%, respectively. No significant difference was observed between the 15-min and 30-min measurement intervals in the low- and high-dose citric acid groups, including patients with results in the gray zone. The low-dose citric acid test, with an optimal measurement interval of 15 min, was highly accurate in the diagnosis of Hp infection in the Chinese population, especially for individuals with results in the gray zone.
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Testes Respiratórios , Isótopos de Carbono , Ácido Cítrico , Infecções por Helicobacter , Helicobacter pylori , Ureia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Respiratórios/métodos , China , População do Leste Asiático , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Sensibilidade e Especificidade , Ureia/análiseRESUMO
Introduction: In recent years, there has been a strong association between transient receptor potential (TRP) channels and the development of various malignancies, drug resistance, and resistance to radiotherapy. Consequently, we have investigated the relationship between transient receptor potential channels and cervical cancer from multiple angles. Methods: Patients' mRNA expression profiles and gene variants were obtained from the TCGA database. Key genes in transient receptor potential channel prognosis-related genes (TRGs) were screened using the least absolute shrinkage and selection operator (LASSO) regression method, and a risk signature was constructed based on the expression of key genes. Various analyses were performed to evaluate the prognostic significance, biological functions, immune infiltration, and response to immunotherapy based on the risk signature. Results: Our research reveals substantial differences between high and low-risk groups in prognosis, tumor microenvironment, tumor mutational load, immune infiltration, and response to immunotherapy. Patients in the high-risk group exhibited poorer prognosis, lower tumor microenvironment scores and reduced response to immunotherapy while showing increased sensitivity to specific targeted drugs. In vitro experiments further illustrated that inhibiting transient receptor potential channels effectively decreased the proliferation, invasion, and migration of cervical cancer cells. Discussion: This study highlights the significant potential of transient receptor potential channels in cervical cancer, emphasizing their crucial role in prognostic prediction and personalized treatment strategies. The combination of TRP inhibitors with immunotherapy and targeted drugs may offer promise for individuals affected by cervical cancer.
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Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and often develops on the foundation of chronic liver disease or cirrhosis. Cirrhosis is a clinically prevalent chronic progressive liver disease characterized by diffuse liver damage resulting from long-term or repeated actions of 1 or more etiological factors. However, the impact of CENPF and nuclear division cycle 80 (NDC80) genes on rehabilitation nursing of HCC and cirrhosis remains unclear. HCC and cirrhosis datasets GSE63898 and GSE89377 profile files were downloaded from the gene expression omnibus database generated on platforms GPL13667 and GPL6947, respectively. Differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), survival analysis, immune infiltration analysis, and comparative toxicogenomics database (CTD) analysis were conducted. Gene expression heatmaps were plotted. miRNAs regulating central DEGs were selected through TargetScan. A total of 626 DEGs were identified. According to gene ontology (GO) analysis, they were primarily enriched in small molecule metabolic processes, drug metabolic processes, binding of identical proteins, and lipid metabolic processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis results indicated that the target genes were mainly enriched in metabolic pathways, phagosomes, glycine, serine, and threonine metabolism. The construction and analysis of the PPI network revealed 3 core genes (NDC80, CENPF, RRM2). Gene expression heatmaps showed that core genes (CENPF, NDC80) were highly expressed in HCC and cirrhosis samples. CTD analysis found that 2 genes (CENPF and NDC80) were associated with liver, jaundice, ascites, fever, dyspepsia, and hepatic encephalopathy. CENPF and NDC80 are highly expressed in HCC and cirrhosis, and CENPF and NDC80 might be the biomarkers of rehabilitation nursing of HCC and cirrhosis.
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Carcinoma Hepatocelular , Proteínas do Citoesqueleto , Cirrose Hepática , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , Cirrose Hepática/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Mapas de Interação de Proteínas , Perfilação da Expressão GênicaRESUMO
Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)-induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin-draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin-draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor-ß (TGFß) messenger RNA (mRNA) and interleukin-23 (IL-23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGFß/PU.1/IL-23 signal axis.
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Células de Langerhans , Psoríase , Animais , Camundongos , Interleucina-23 , Fator de Crescimento Transformador beta1 , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Fator de Crescimento Transformador beta , RNA MensageiroRESUMO
Background: Cervical cancer (CC) remains one of the most common and deadly malignancies in women worldwide. FBXO5, a protein-coding gene, is highly expressed in a variety of primary tumors and promotes tumor progression, however, its role and prognostic value in CC remain largely unknown. Methods: A key differential gene, FBXO5, was screened according to WGCNA based on immunohistochemical assays of clinical samples, multiple analyses of the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, including survival analysis, tumor mutational burden, GO, KEGG, tumor immune infiltration, and chemotherapeutic drug sensitivity, to explore the expression and prognostic value of FBXO5 in CC. The migration and invasiveness of cervical cancer cells following FBXO5 knockdown and overexpression were examined using wound healing and transwell assays, and the viability of cancer cells was assessed using CCK8 and EdU assays. Results: FBXO5 was discovered to be substantially expressed in CC tissues using data from our CC cohort and the TCGA database, and a survival analysis indicated FBXO5 as a predictive factor for poor overall survival in CC patients. In vitro, CC cells were more inclined to proliferate, migrate, and invade when FBXO5 was upregulated as opposed to when it was knocked down.
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BACKGROUND AND OBJECTIVE: The pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Homocysteine may reduce the compliance of intracranial arteries and damage the endothelial function of the blood-brain barrier (BBB), which may be the underlying mechanism of iNPH. The overlap cases between deep perforating arteriopathy (DPA) and iNPH were not rare for the shared risk factors. We aimed to investigate the relationship between serum homocysteine and iNPH in DPA. METHODS: A total of 41 DPA patients with iNPH and 49 DPA patients without iNPH were included. Demographic characteristics, vascular risk factors, laboratory results, and neuroimaging data were collected. Multivariable logistic regression analysis was performed to investigate the relationship between serum homocysteine and iNPH in DPA patients. RESULTS: Patients with iNPH had significantly higher homocysteine levels than those without iNPH (median, 16.34 mmol/L versus 14.28 mmol/L; P = 0.002). There was no significant difference in CSVD burden scores between patients with iNPH and patients without iNPH. Univariate logistic regression analysis demonstrated that patients with homocysteine levels in the Tertile3 were more likely to have iNPH than those in the Tertile1 (OR, 4.929; 95% CI, 1.612-15.071; P = 0.005). The association remained significant after multivariable adjustment for potential confounders, including age, male, hypertension, diabetes mellitus, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia, and eGFR level. CONCLUSION: Our study indicated that high serum homocysteine levels were independently associated with iNPH in DPA. However, further research is needed to determine the predictive value of homocysteine and to confirm the underlying mechanism between homocysteine and iNPH.
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Hidrocefalia de Pressão Normal , Doenças Vasculares , Humanos , Masculino , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/complicações , Estudos Transversais , Doenças Vasculares/complicações , Fatores de Risco , NeuroimagemRESUMO
Since chemotherapy's therapeutic impact is diminished by drug resistance, treating ovarian cancer is notably challenging. Thereafter, it is critical to develop cutting-edge approaches to treating ovarian cancer. Baohuoside I (derived from Herba Epimedii) is reported to have antitumor properties in various malignancies. It is unknown, however, what role Baohuoside I plays in cisplatin (DDP)-resistant ovarian cancer cells. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), colony formation, and flow cytometry assay were used to investigate the impact of Baohuoside I on ovarian cancer A2780 cells and DDP-resistant A2780 (A2780/DDP) cells. The level of microtubule associated protein 1 light chain 3 (LC3) was determined using immunofluorescence staining. Utilizing the mRFP-GFP-LC3B tandem fluorescent probe allowed us to analyse the autophagy flux. Analysis of mRNA and protein level was performed using RT-qPCR and Western blot analysis, respectively. The interaction between hypoxia inducible factor 1 subunit alpha (HIF-1α) and autophagy related 5 (ATG5) promoter was investigated by dual luciferase and ChIP assay. Additionally, evaluation of Baohuoside I's role in ovarian cancer was performed using a nude mouse xenograft model. Baohuoside I decreased the viability and proliferation and triggered the apoptosis of both A2780 and A2780/DDP cells in a concentration-dependent manner. Baohuoside I also increased the sensitivity of A2780/DDP cells to DDP. Concurrently, HIF-1α could promote A2780/DDP cells resistance to DDP. In addition, HIF-1α could induce the autophagy of A2780/DDP cells through transcriptionally activating ATG5, and Baohuoside I imporved the chemosensitivity of A2780/DDP cells to DDP by downregulating HIF-1α. Moreover, Baohuoside I could inhibit the chemoresistance to DDP in ovarian cancer in vivo. Baohuoside I sensitizes ovarian cancer cells to DDP by suppressing autophagy via downregulating the HIF-1α/ATG5 axis. Consequently, Baohuoside I might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of drug treatment for ovarian cancer.
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Antineoplásicos , Neoplasias Ovarianas , Animais , Camundongos , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Autofagia , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Proteína 5 Relacionada à AutofagiaRESUMO
Background: Lymphatic metastasis is a common phenomenon of cervical cancer. Tumor necrosis factor-α (TNF-α) was found to be closely associated with lymphatic cancer metastasis. However, the mechanism through which TNF-α regulates lymphatic metastasis in cervical cancer remains unclear. Methods: In this study, cervical cancer cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with or without TNF-α for 48 h, and then the corresponding conditional medium (CM-TNF-α or CM) was collected. The level of vascular endothelial growth factor (VEGFC) in the corresponding CM was then detected using an enzyme-linked immunosorbent assay (ELISA). Next, human lymphatic endothelial cells (HLECs) were cultured in CM-TNF-α or CM for 48 h. Cell viability was measured using the cell counting kit-8 (CCK-8) assay, and angiogenesis was detected using a tube formation assay. Subsequently, the expressions of AKT, p-AKT, ERK, and p-ERK in HLECs were detected using western blotting. In addition, to further investigate the effect of TNF-α on the progression of cervical cancer, a C33A subcutaneous xenograft model was established in vivo. Results: We found that TNF-α significantly stimulated cervical cancer cells to secrete VEGFC. Additionally, the CM collected from the TNF-α-treated cervical cancer cells notably promoted the proliferation, migration, and angiogenesis of HLECs; however, these changes were reversed by MAZ51, a VEGFR3 inhibitor. Moreover, TNF-α obviously elevated D2-40 and VEGFC protein expressions in tumor tissues, promoting lymphangiogenesis and lymphatic metastasis in vivo. Meanwhile, TNF-α markedly upregulated p-AKT and p-ERK expressions in tumor tissues, whereas these changes were reversed by MAZ51. Conclusion: Collectively, TNF-α could promote tumorigenesis, lymphangiogenesis, and lymphatic metastasis in vitro and in vivo in cervical cancer via activating VEGFC-mediated AKT and ERK pathways. These results may provide new directions for the treatment of cervical cancer.
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Neoplasias do Colo do Útero , Feminino , Humanos , Carcinogênese/metabolismo , Transformação Celular Neoplásica/metabolismo , Células Endoteliais/metabolismo , Linfangiogênese , Metástase Linfática/patologia , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias do Colo do Útero/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Among gynecological malignancies, ovarian cancer has the highest mortality rate and has sparked widespread interest in studying the mechanisms underlying ovarian cancer development. Based on TCGA and GEO databases, we investigated the highly expressed autophagy-related genes that determine patient prognosis using limma differential expression and Kaplan-Meier survival analyses. The biological processes associated with these genes were also predicted using GO/KEGG functional enrichment analysis. CCK-8, cell scratch, and transwell assays were used to investigate the effects of PXN on the proliferation, migration, and invasion abilities of ovarian cancer cells. Transmission electron microscopy was used to observe the autophagosomes. The expression of autophagy proteins and the PI3K/Akt/mTOR and p110ß/Vps34/Beclin1 pathway proteins in ovarian cancer cells was detected using western blot; autophagy protein expression was further detected and localized using cellular immunofluorescence. A total of 724 autophagy-related genes were found to be overexpressed in ovarian -cancer tissues, with high expression of PEX3, PXN, and RB1 associated with poor prognosis in patients (p < .05). PXN activates and regulates signaling pathways related to cellular autophagy, ubiquitination, lysosomes, PI3K-Akt, and mTOR. Autophagosomes were observed in all cell groups. The increase in PXN gene expression promoted the proliferation, migration, and invasion of ovarian cancer cells, increased the expression of SQSTM1/p62 protein, decreased LC3II/LC3â , inhibited the phosphorylation of Akt and mTOR proteins, and suppressed the expression of PI3K(p110ß) and Beclin1 proteins. The decrease in PXN expression also confirmed these changes. Thus, PXN is highly expressed during ovarian cancer and is associated with poor patient prognosis. It may promote ovarian cancer cell proliferation, migration, and invasion by inhibiting cellular autophagy via suppression of the p110ß/Vps34/Beclin1 pathway.
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Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Humanos , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Neoplasias Ovarianas/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Proliferação de Células , Linhagem Celular Tumoral , Apoptose , Paxilina/metabolismo , Paxilina/farmacologiaRESUMO
Exosomal miRNAs are known to play important roles in ovarian cancer and chemotherapeutic resistance. However, a systematic evaluation of characteristics of exosomal miRNAs involved in cisplatin resistance in ovarian cancer remains totally unclear. Exosomes (Exo-A2780, Exo-A2780/DDP) were extracted from cisplatin-sensitive cells (A2780) and cisplatin-resistant cells (A2780/DDP). Differential exosomal miRNA expression profiles were found by high-throughput sequencing (HTS). Target genes of the exo-miRNAs were predicted by using two online databases to increase the prediction accuracy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to find biological relationships with chemoresistance. RTâqPCR of three exosomal miRNAs was performed, and a proteinâprotein interaction (PPI) network was established to identify the hub genes. The GDSC database was used to prove the association between hsa-miR-675-3p expression and the IC50 value. An integrated miRNA-mRNA network was constructed to predict miRNA-mRNA associations. The connection between hsa-miR-675-3p and ovarian cancer was discovered by immune microenvironment analyses. The upregulated exosomal miRNAs could regulate gene targets through signalling pathways such as the Ras, PI3K/Akt, Wnt, and ErbB pathways. GO and KEGG analyses indicated that the target genes were involved in protein binding, transcription regulator activity and DNA binding. The RTâqPCR results were consistent with the HTS data, and the results of PPI network analysis suggested that FMR1 and CD86 were the hub genes. GDSC database analysis and construction of the integrated miRNA-mRNA network suggested that hsa-miR-675-3p was associated with drug resistance. Immune microenvironment analyses showed that hsa-miR-675-3p was crucial in ovarian cancer. The study suggested that exosomal hsa-miR-675-3p is a potential target for treating ovarian cancer and overcoming cisplatin resistance.
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MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , Microambiente Tumoral , Proteína do X Frágil da Deficiência IntelectualRESUMO
Background: Immunogenic cell death (ICD) can reshape the immune microenvironment of tumors. Driven by stressful pressure, by directly destroying tumor cells and activating the body's adaptive immunity, ICD acts as a modulator of cell death, enabling the body to generate an anti-tumor immune response that produces a more effective therapeutic effect, while tumor cells are driven to kill. Hence, this research aimed to find and evaluate ICD-related genetic signatures as cervical cancer (CC) prognostic factors. Methods: Data of CC patients from the Tumor Genome Atlas (TCGA) were used as the basis to obtain immunogenic cell-death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated. Results: A prognostic model with four IPGs (PDIA3, CASP8, IL1, and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPGs expression had a lower survival rate. Single and multifactor Cox regression analysis also showed that this risk score was a reliable predictor of overall survival. In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group. Conclusion: A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients.
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OBJECTIVE: Polo-like kinase 1 (PLK1), a serine/threonine-protein kinase, functions as a potent oncogene in the initiation and progression of tumor. The aim of this study is to assess potential correlations between PLK1 expression and immune infiltration in breast cancer (BRCA) and construct a PLK1-based immune risk model applicable for prognosis and treatment response prediction in BRCA. METHODS: We collected data on PLK1 gene expression in BRCA patients from The Cancer Genome Atlas (TCGA) database. Thereafter, we analyzed the associations of PLK1 expression with immune cell infiltration and immunomodulators, and established a prognostic risk model based on seven PLK1-associated immunomodulator genes and a nomogram for survival prediction. RESULTS: BRCA prognosis, clinical stage progression, and tumor classification were all shown to be substantially correlated with PLK1 expression. The PLK1 gene was significantly enriched in T cell and B cell receptors and molecules of the chemokine signaling pathways. Specifically, PLK1 expression was positively correlated with the CD8+ T cell and regulatory T cell (Tregs) activation and negatively correlated with M2 macrophage infiltration. The seven-genes-based risk model could serve as an independent prognostic factor of BRCA. The risk model was markedly correlated with the expression of programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1; both p < 0.001) immune checkpoints, and tumor mutation burden (TMB). High- and low-risk BRCA patients identified by the risk model responded differently to anti-PD-1 and/or anti-CTLA4 therapy, as well as common chemotherapy drugs, like cisplatin, paclitaxel, and gemcitabine. CONCLUSION: This PLK1-based immune risk model can effectively predict the prognosis and tumor progression of BRCA, identify gene mutations, and evaluate patient's response toward immunotherapy and chemotherapy regimens.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Prognóstico , Quinase 1 Polo-LikeRESUMO
Cuproptosis (copper-ion-dependent cell death) is an unprogrammed cell death, and intracellular copper accumulation, causing copper homeostasis imbalance and then leading to increased intracellular toxicity, which can affect the rate of cancer cell growth and proliferation. This study aimed to create a newly cuproptosis-related lncRNA signature that can be used to predict survival and immunotherapy in patients with cervical cancer, but also to predict prognosis in patients treated with radiotherapy and may play a role in predicting radiosensitivity. First of all, we found lncRNAs associated with cuproptosis between cervical cancer tumor tissues and normal tissues. By LASSO-Cox analysis, overlapping lncRNAs were then used to construct lncRNA signatures associated with cuproptosis, which can be used to predict the prognosis of patients, especially the prognosis of radiotherapy patients, ROC curves and PCA analysis based on cuprotosis-related lncRNA signature and clinical signatures were developed and demonstrated to have good predictive potential. In addition, differences in immune cell subset infiltration and differences in immune checkpoint expression between high-risk and low-risk score groups were analyzed, and we investigated the relationship between this signature and tumor mutation burden. In summary, we constructed a lncRNA prediction signature associated with cuproptosis. This has important clinical implications, including improving the predictive value of cervical cancer patients and providing a biomarker for cervical cancer.
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BACKGROUND: Metabolism dysfunction can affect the biological behavior of tumor cells and result in carcinogenesis and the development of various cancers. However, few thoughtful studies focus on the predictive value and efficacy of immunotherapy of metabolism-related gene signatures in endometrial cancer (EC). This research aims to construct a predictive metabolism-related gene signature in EC with prognostic and therapeutic implications. METHODS: We downloaded the RNA profile and clinical data of 503 EC patients and screened out different expressions of metabolism-related genes with prognosis influence of EC from The Cancer Genome Atlas (TCGA) database. We first established a metabolism-related genes model using univariate and multivariate Cox regression and Lasso regression analysis. To internally validate the predictive model, 503 samples (entire set) were randomly assigned into the test set and the train set. Then, we applied the receiver operating characteristic (ROC) curve to confirm our previous predictive model and depicted a nomogram integrating the risk score and the clinicopathological feature. We employed a gene set enrichment analysis (GSEA) to explore the biological processes and pathways of the model. Afterward, we used ESTIMATE to evaluate the TME. Also, we adopted CIBERSORT and ssGSEA to estimate the fraction of immune infiltrating cells and immune function. At last, we investigated the relationship between the predictive model and immune checkpoint genes. RESULTS: We first constructed a predictive model based on five metabolism-related genes (INPP5K, PLPP2, MBOAT2, DDC, and ITPKA). This model showed the ability to predict EC patients' prognosis accurately and performed well in the train set, test set, and entire set. Then we confirmed the predictive signature was a novel independent prognostic factor in EC patients. In addition, we drew and validated a nomogram to precisely predict the survival rate of EC patients at 1-, 3-, and 5-years (ROC1-year = 0.714, ROC3-year = 0.750, ROC5-year = 0.767). Furthermore, GSEA unveiled that the cell cycle, certain malignant tumors, and cell metabolism were the main biological functions enriched in this identified model. We found the five metabolism-related genes signature was associated with the immune infiltrating cells and immune functions. Most importantly, it was linked with specific immune checkpoints (PD-1, CTLA4, and CD40) that could predict immunotherapy's clinical response. CONCLUSION: The metabolism-related genes signature (INPP5K, PLPP2, MBOAT2, DDC, and ITPKA) is a valuable index for predicting the survival outcomes and efficacy of immunotherapy for EC in clinical settings.
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Neoplasias do Endométrio , Humanos , Feminino , Carcinogênese , Ciclo Celular , Mineração de Dados , Bases de Dados FactuaisRESUMO
Intrauterine adhesion (IUA) is a gynaecological disease caused by uterine cavity surgeries and infections that leads to partial or total occlusion of the uterine cavity. However, the underlying mechanism(s) and progression of the disease have not yet been identified. IUA has a high recurrence rate and poor prognosis, and effective drugs to prevent adhesion are lacking. Therefore, establishing an effective animal model of IUA is of great significance for revealing the pathogenesis of IUA and the mechanism(s) governing drug effects. Rats, mice, rabbits, and other animals are currently used to establish intrauterine adhesion models. The IUA induction methods include chemical, thermal, or mechanical damage and mechanical damage combined with an infective method. We analysed the advantages and disadvantages of various models and their clinical simulations in order to provide a precise animal model for exploring the pathogenesis, treatment strategies, and prevention of IUA.
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Endométrio , Doenças Uterinas , Feminino , Humanos , Ratos , Animais , Camundongos , Coelhos , Endométrio/patologia , Doenças Uterinas/patologia , Útero/patologia , Modelos Animais de Doenças , Aderências Teciduais/patologiaRESUMO
Four actinomycete strains isolated from the coral Acropora austera and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring similar ultraviolet absorption based on the analysis of HPLC and LC-MS. The production titers of halogenated compounds from Streptomyces diacarni SCSIO 64983 exceeded those of other similar strains leading us to focus on SCSIO 64983. Four new thiocarbazomycins A-B (1-2), chlocarbazomycin E (3), and brocarbazomycin A (4), together with three known chlocarbazomycins A-C (5-7) containing a carbazole core were identified, and their structures were determined using a combination of spectroscopic analysis including HRESIMS, 1D and 2D NMR. Structurally speaking, compounds 1 and 2 have the rare sulfur-containing carbazole nuclei, and 3 and 4 contain Cl and Br atoms, respectively. Although these compounds have not yet been found to have obvious biological activity, their discovery highlights the role of molecular libraries in subsequent drug discovery campaigns.
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Actinobacteria , Antozoários , Actinobacteria/química , Actinomyces , Animais , Carbazóis , Recifes de Corais , AreiaRESUMO
Paraquat (PQ) has high acute toxicity, even at low concentrations. For most people, the main pathway of exposure to PQ is through the diet. Therefore, the development of simple and efficient methods for PQ testing is critical for ensuring food safety. In this study, a new electrochemical detection strategy for paraquat is proposed based on the specific binding of PQ to its nucleic acid aptamer. Firstly, the Zn/Fe bimetallic ZIF derived nanoporous carbon (Zn/Fe-ZIF-NPC) and nickel hexacyanoferrate nanoparticles (NiHCF-NPs) were sequentially modified onto the glassy carbon electrode (GCE). NiHCF-NPs served as the signal probes, while Zn/Fe-ZIF-NPC facilitated electron transfer and effectively enhanced the sensing signal of NiHCF-NPs. Au nanoparticles (AuNPs) were then electrodeposited on the NiHCF-NPs/Zn/Fe-ZIF-NPC/GCE and then the thiolated aptamer was assembled on the AuNPs/NiHCF-NPs/Zn/Fe-ZIF-NPC/GCE via Au-S bonding. When incubated with PQ, the formation of PQ-aptamer complexes delayed the interfacial electron transport reaction of NiHCF-NPs, which caused a decrease in the current signals. As a result, simple and highly sensitive detection of PQ can be readily achieved by detecting the signal changes. A linear range was obtained from 0.001 to 100 mg/L with a detection limit as low as 0.34 µg/L. Due to the recognition specificity of the aptamer to its target molecule, the proposed method has excellent anti-interference ability. The prepared electrochemical aptasensor was successfully used for PQ assay in lettuce, cabbage and agriculture irrigation water samples with recoveries ranging from 96.20% to 104.02%, demonstrating the validity and practicality of the proposed method for PQ detection in real samples.
RESUMO
In ovarian carcinogenesis and progression, long non-coding RNAs (lncRNAs) have been shown to have a role, although the underlying processes remain a mystery. By modulating the degree of autophagy in ovarian cancer cells, we sought to learn more about the function lncRNA HOXA11-AS plays in the development of ovarian cancer. The expression of HOXA11-AS in ovarian normal cells and ovarian cancer cell lines was measured using R package and qRT-PCR. Ovarian cancer cells expressed HOXA11-AS substantially higher than normal cells, while cisplatin-resistant cells expressed HOXA11-AS significantly higher than ovarian cancer cells. Next, we studied the prognostic data of HOXA11-AS in ovarian cancer in the Tissue Cancer Genome Atlas (TCGA). In the next step, lentiviral transfection of ovarian cancer cells A2780, OVCAR3, and A2780/DDP (cisplatin-resistant) were performed, and HOXA11-AS knockdown was found to significantly inhibit cell viability, migration, and invasion of A2780 and OVCAR3 cells, and promote apoptosis by CCK-8 assay, transwell assay, cell cycle, and apoptosis assay, and promoted the sensitivity of A2780/DDP cells to cisplatin. It has been shown by the western blot test that HOXA11-AS knockdown increases the amount of cellular autophagy in cells. In contrast, adding the autophagy inhibitor 3-methyladenine (3-MA) to HOXA11-AS cells knocked down in vivo reduced its anti-tumor properties. As a whole, this study found that HOXA11-AS knockdown increased the expression of autophagy-related proteins and improved cisplatin sensitivity, decreased ovarian cancer cell proliferation, and promoted cell apoptosis. This study provides new insights into the role of HOXA11-AS in ovarian cancer regulation.