RESUMO
BACKGROUND: Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD-related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction. METHOD: We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome-based CRC prognostic models. RESULT: Our integrated model successfully identified differentially expressed PCD-related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high-risk and low-risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis. CONCLUSION: The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC.
Assuntos
Apoptose , Neoplasias Colorretais , Humanos , Prognóstico , Aprendizado de Máquina , Neoplasias Colorretais/genéticaRESUMO
The rotate vector (RV) reducer has a complex structure and highly coupled internal components. Acoustic emission (AE) signal, which is more sensitive to a weak fault, is selected for fault diagnosis of the RV reducer. The high sampling frequency and big data are the challenges for AE signal store and analysis. This study combines compressed sensing (CS) and convolutional neural networks. As a result, data redundancy is significantly reduced while retaining most of the information, and the analysis efficiency is improved. Firstly, the time-domain AE signal was projected into the compression domain to obtain the compression signal; then, the wavelet packet decomposition in the compressed domain was performed to obtain the information of each frequency band. Next, the frequency band information was sent into the input layer of the multi-channel convolutional layer, and the energy pooling layer mines the energy characteristics of each frequency band. Finally, the softmax classifier was used to classify and predict different fault types of RV reducers. The self-fabricated RV reducer experimental platform was used to verify the proposed method. The experimental results show that the proposed method can effectively extract the fault features in the AE signal of the RV reducer, improve the efficiency of signal processing and analysis, and achieve the accurate classification of RV reducer faults.
Assuntos
Algoritmos , Compressão de Dados , Acústica , Redes Neurais de Computação , Processamento de Sinais Assistido por ComputadorRESUMO
In fault diagnosis research, compound faults are often regarded as an isolated fault mode, while the association between compound faults and single faults is ignored, resulting in the inability to make accurate and effective diagnoses of compound faults in the absence of compound fault training data. In an examination of the rotate vector (RV) reducer, a core component of industrial robots, this paper proposes a compound fault identification method that is based on an improved convolutional capsule network for compound fault diagnosis of RV reducers. First, one-dimensional convolutional neural networks are used as feature learners to deeply mine the feature information of a single fault from a one-dimensional time-domain signal. Then, a capsule network with a two-layer stack structure is designed and a dynamic routing algorithm is used to decouple and identify the single fault characteristics for compound faults to undertake the diagnosis of compound faults of RV reducers. The proposed method is verified on the RV reducer fault simulation experimental bench, the experimental results show that the method can not only diagnose a single fault, but it is also possible to diagnose the compound fault that is composed of two types of single faults through the learning of two types of single faults of the RV reducer when the training data of the compound faults of the RV reducer are missing. At the same time, the proposed method is used for compound fault diagnosis of bearings, and the experimental results confirm its applicability.
RESUMO
Background: Osteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model. Method: We retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments. Result: In our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes-CLTCL1, EDIL3, and SQLE-resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets. Conclusion: The five genes constituting the OS-PCDS model-CLTCL1, MTM1, MLH1, EDIL3, and SQLE-were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.
Assuntos
Apoptose , Neoplasias Ósseas , Osteossarcoma , Osteossarcoma/genética , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Humanos , Apoptose/genética , Prognóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/mortalidade , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Aprendizado de Máquina , Perfilação da Expressão Gênica , Transcriptoma , Proliferação de Células/genética , Bases de Dados Genéticas , Biologia Computacional/métodosRESUMO
Toxicologic studies reported that organophosphate esters (OPEs) may disrupt lipid metabolism, thus affecting serum lipid levels. However, epidemiological evidence regarding the association between OPEs and the risk of hyperlipidemia (HPL) as well as serum lipid levels is scarce. In the present study, our aim was to investigate the impact of individual and mixed OPE exposure on HPL. A total of 1981 Chinese adults were involved based on a cross-sectional design. Overall, we found a positive association between bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and the risk of HPL. Bis(1-chloro-2-propyl) phosphate (BCIPHIPP) showed a positive association with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). BDCIPP, diphenyl phosphate (DPHP), di-ocresyl phosphate and di-p-cresyl phosphate (Docp&Dpcp), and 4-hydroxyphenyl-diphenyl phosphate (4-OH-DPHP) exhibited a negative association with high-density lipoprotein cholesterol (HDL-C). In stratified analyses, BDCIPP and BCIPHIPP were significantly correlated with the increased risk of HPL in the age ≤ 45 group. Bis(2-butoxyethyl) phosphate (BBOEP) was in relationship with an elevated risk of HPL in the subgroup of BMI < 24 kg/m2. BDCIPP was also positively associated with HPL in men. Quantile-based g computation (qgcomp) and generalized weighted quantile sum regression (gWQS) models demonstrated a negative association between OPEs mixed exposure and HDL-c in the total population, as well as a positive effect of them on HPL in the subgroup of age ≤ 45 years, which is consistent with the individual analyses. Furthermore, joint effect analyses revealed that participants with detected BDCIPP urinary levels and unhealthy lifestyles had the highest risk of HPL. Our findings offer evidence supporting the correlation between exposure to OPE and the risk of HPL, necessitating further prospective studies for validation.
Assuntos
Ésteres , Hiperlipidemias , Lipídeos , Organofosfatos , Humanos , China , Hiperlipidemias/epidemiologia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Lipídeos/sangue , Exposição AmbientalRESUMO
Exposure to environmental contaminants and the development of hypertension and diabetes represent crucial risk factors for chronic kidney disease (CKD). Toxicological studies have revealed that organophosphate esters (OPEs) impair kidney function. However, the joint effects of OPE exposure on kidney injury and the interactions of OPE exposure with hypertension or diabetes on kidney injury remain unclear. Our study aimed to investigate the individual and joint effects of OPE exposure on renal injury, as well as the potential interaction between OPE exposure and hypertension or diabetes on kidney injury. The study enrolled 1938 participants from Wuhan, China. To explore the relationship between OPE exposure and renal injury, we conducted multivariate linear and logistic regression analysis. The results indicated that each unit increase in 4-hydroxyphenyl diphenyl phosphate (4-HO-DPHP), bis(2-butoxyethyl) phosphate (BBOEP), and tris(2-chloroethyl) phosphate (TCEP) (1 µg/L-ln transformed) was associated with a decreased 0.57 mL/min/1.73 m2 (95%CI: -1.05, -0.09), 0.85 mL/min/1.73 m2 (95%CI: -1.52, -0.19) and 1.24 mL/min/1.73 m2 (95%CI: -2.26, -0.23) of estimated glomerular filtration rate (eGFR), while each unit increase in 4-HO-DPHP and BBOEP (1 µg/L-ln transformed) was associated with 14% and 20% elevation of incident impaired renal function (IRF) risk. Notably the highest tertile of BCIPHIPP was positively associated with eGFR, although the p for trend ï¼ 0.05. We employed Bayesian kernel machine regression (BKMR) and quartile-based g-computation (qgcomp) models to explore the joint effects of OPE mixtures on eGFR and IRF. Both the results of BKMR and qgcomp model consistently demonstrated negative associations between OPE mixtures and eGFR, and TCEP and 4-HO-DPHP were major contributors. Furthermore, we observed multiplicative interactions of diphenyl phosphate (DPHP), BBOEP, di-ocresyl phosphate (DoCP) & di-p-cresyl phosphate (DpCP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and hypertension or diabetes on kidney injury (all Pï¼0.05). Those with diabetes or hypertension and higher OPE metabolite concentrations had increased risk of kidney function impairment compared to those who did not have diabetes or hypertension. These findings suggest that specific OPE exposure may elevate the risk of renal injury, particularly among hypertensive and diabetic populations.
Assuntos
Diabetes Mellitus , Hipertensão , Organofosfatos , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , China/epidemiologia , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Organofosfatos/toxicidade , Adulto , Diabetes Mellitus/epidemiologia , Ésteres , Poluentes Ambientais/toxicidade , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Idoso , Exposição Ambiental/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , População do Leste AsiáticoRESUMO
Rapid industrial and agricultural developments in China have led to the wide use and discharge of chemical products and pesticides, resulting in extensive residues in environmental media. These residues can enter the human body through various pathways, leading to high exposure risks and health hazards. Because the human body is exposed to a variety of chemical pollutants, accurately quantifying the exposure levels of these pollutants in the human body and evaluating their health risks are of great importance. In this study, the serum concentrations of 97 typical chemical pollutants of 60 adults in central China were simultaneously determined using solid-phase extraction coupled with gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS). In this method, 200 µL of a serum sample was mixed with 10 µL of an isotope-labeled internal standard solution. The sample was vortexed and refrigerated overnight at 4 â. Each sample was then deproteinized by the addition of 200 µL of 15% formic acid aqueous solution and vortexed. The serum sample was loaded into a preconditioned Oasis® PRiME HLB SPE cartridge and rinsed with 3 mL of methanol-water (6â¶1, v/v). The SPE cartridge was subsequently vacuumed. The analytes were eluted with 3 mL of dichloromethane followed by 3 mL of n-hexane. The eluent was concentrated to near dryness under a gentle nitrogen stream and reconstituted with 100 µL of acetone. The samples were determined by GC-MS/MS and separated on a DB-5MS capillary column (30 m×0.25 mm×0.25 µm) with temperature programming. The column temperature was maintained at 70 â for 2 min, increased at a rate of 25 â/min to 150 â, increased at a rate of 3 â/min to 200 â, and then held for 2 min. Finally, the column temperature was increased at a rate of 8 â/min to 300 â and maintained at this temperature for 8 min. The samples were detected in multiple-reaction monitoring (MRM) mode and quantitatively analyzed using the internal standard method. Multiple linear regression models were used to analyze the effects of demographic characteristics, lifestyle habits, and diet on the concentrations of the chemical pollutants in the serum samples, and known biomonitoring equivalents (BEs) and human biomonitoring (HBM) values were combined to compute hazard quotients (HQs) and hazard indices (HIs) and evaluate the health risks of single and cumulative exposures to the chemical pollutants. The results showed that the main pollutants detected in human serum were organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The detection rates of eight pollutants, including hexachlorobenzene (HCB) (100%), pentachlorophenol (PCP) (100%), p,p'-dichlorodiphenylene (p,p'-DDE) (100%), PCB-138 (100%), PCB-153 (98.3%), ß-hexachlorocyclohexane (ß-HCH) (91.7%), fluorene (Flu) (85.0%), and anthracene (Ant) (75.0%), were greater than 70%. The serum levels of ß-HCH were higher in females than in males, and age was positively correlated with exposure to p,p'-DDE, PCB-138, PCB-153, and ß-HCH. Increased exposure levels to p,p'-DDE and ß-HCH may be associated with a high frequency of meat intake, whereas increased exposure level to PCP may be associated with a high frequency of vegetable intake. The serum HQ of PCP was greater than 1 in 6.7% of the samples, and no risk was observed for HCB and p,p'-DDE exposure in the study population. Approximately 28.3% of the study subjects had HI values greater than 1. Overall, the general adult population in this region is widely exposed to a wide range of chemical pollutants, and gender, age, and diet are likely to be the main factors influencing the concentration of chemical pollutants. The health risk of single and compound exposures to chemical pollutants should not be ignored.
Assuntos
Poluentes Ambientais , Hexaclorocicloexano , Hidrocarbonetos Clorados , Pentaclorofenol , Praguicidas , Bifenilos Policlorados , Adulto , Masculino , Feminino , Humanos , Poluentes Ambientais/análise , Diclorodifenil Dicloroetileno/análise , Diclorodifenil Dicloroetileno/metabolismo , Hexaclorobenzeno/análise , Espectrometria de Massas em Tandem , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Bifenilos Policlorados/análise , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Pentaclorofenol/análise , Medição de RiscoRESUMO
Exposure to organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) has been reported to be associated with renal impairment and chronic kidney disease (CKD). Nevertheless, the research results thus far have exhibited inconsistency, and the effect of lifestyle on their association is not clear. In this study, we assessed the correlation between serum OCPs/PCBs and CKD and renal function indicators including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) among 1721 Chinese adults. In order to further investigate the potential impact of lifestyle, we conducted joint associations of lifestyle and OCPs/PCBs on CKD. We found a negative correlation between p,p'-DDE and eGFR, while logistic regression results showed a positive correlation between PCB-153 and CKD (OR, 1.92; 95% CI, 1.21, 3.06). Quantile g-computation regression analyses showed that the association between co-exposure to OCPs/PCBs and CKD was not significant, but p,p'-DDE and PCB-153 were the main contributors to the negative and positive co-exposure effects of eGFR and CKD, respectively, which is consistent with the regression results. Participants with both relatively high PCB-153 exposure and an unhealthy lifestyle had the highest risk of CKD, in the joint association analysis. The observed associations were generally supported by the FAS-eGFR method. Our research findings suggest that exposure to OCPs/PCBs may be associated with decreased eGFR and increased prevalence of CKD in humans, and a healthy lifestyle can to some extent alleviate the adverse association between PCB-153 exposure and CKD.
Assuntos
Hidrocarbonetos Clorados , Estilo de Vida , Praguicidas , Bifenilos Policlorados , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Bifenilos Policlorados/sangue , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Exposição Ambiental , Taxa de Filtração Glomerular , China , Idoso , Poluentes AmbientaisRESUMO
Organophosphate esters (OPEs), used as flame retardants and plasticizers, have been indicated to impair growth and development in toxicological studies, but current epidemiological data on their associations with body mass index (BMI) are limited and the underlying biological mechanisms remain unclear. In this study, we aim to explore the association of OPE metabolites with BMI z-score, and assess whether sex hormones mediate the relationships between OPE exposure and BMI z-score. We measured weight and height, and determined OPE metabolites in spot urine samples and sex hormones in serum samples among 1156 children and adolescents aged 6-18 years in Liuzhou city, China. The results showed that di-o-cresyl phosphate and di-pcresyl phosphate (DoCP & DpCP) levels were associated with lower BMI z-score of all participants and a similar pattern of associations were presented in prepubertal boys stratified by sex-puberty groups and male children stratified by sex-age groups. In addition, sex hormone binding globulin (SHBG) were related to reduced BMI z-score among all subgroups including prepubertal boys, prepubertal girls, pubertal boys, and pubertal girls (all Ptrend<0.05). We also found that DoCP & DpCP showed positive associations with SHBG among prepubertal boys. Mediation analysis further showed that SHBG mediated 35.0% of the association between DoCP & DpCP and reduced BMI z-score in prepubertal boys. Our results indicated that OPEs may impair growth and development by disrupting the sex hormones in prepubertal boys.
Assuntos
Retardadores de Chama , Hormônios Esteroides Gonadais , Feminino , Humanos , Masculino , Criança , Adolescente , Índice de Massa Corporal , Organofosfatos/metabolismo , Fosfatos , Retardadores de Chama/análise , ÉsteresRESUMO
Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.
Assuntos
Neoplasias da Mama Masculina , Humanos , Feminino , Masculino , Análise da Expressão Gênica de Célula Única , Terapia de Imunossupressão , Metabolismo dos Lipídeos/genética , Ácidos GraxosRESUMO
Background: Cuproptosis, a newly defined regulated form of cell death, is mediated by the accumulation of copper ions in cells and related to protein lipoacylation. Seven genes have been reported as key genes of cuproptosis phenotype. Cuproptosis may be developed by subsequent research as a target to treat cancer, such as breast cancer. Long-noncoding RNA (lncRNA) has been proved to play a vital role in regulating the biological process of breast cancer. However, the role of lncRNAs in cuproptosis is poorly studied. Methods: Based on TCGA (The Cancer Genome Atlas) database and integrated several R packages, we screened out 153 cuproptosis-related lncRNAs and constructed a novel cuproptosis-related prognostic 2-lncRNAs signature (BCCuS) in breast cancer and then verified. By using pRRophetic package and machine learning, 72 anticancer drugs, significantly related to the model, were screened out. qPCR was used to detect the differentially expression of two model lncRNAs and seven cuproptosis genes between 10 pairs of breast cancer tissue samples and adjacent samples. Results: We constructed a novel cuproptosis-related prognostic 2-lncRNAs (USP2-AS1, NIFK-AS1) signature (BCCuS) in breast cancer. Univariate COX analysis (p < .001) and multivariate COX analysis (p < .001) validated that BCCuS was an independent prognostic factor for breast cancer. Overall survival Kaplan Meier-plotter, ROC curve and Risk Plot validated the prognostic value of BCCuS both in test set and verification set. Nomogram and C-index proved that BCCuS has strong correlation with clinical decision-making. BCCuS still maintain inspection efficiency when patients were splitting into Stage I-II (p = .024) and Stage III-IV (p = .003) breast cancer. BCCuS-high group and BCCuS-low group showed significant differences in gene mutation frequency, immune function, TIDE (tumor immune dysfunction and exclusion) score and other phenotypes. TMB (tumor mutation burden)-high along with BCCuS-high group had the lowest Survival probability (p = .005). 36 anticancer drugs whose sensitivity (IC50) was significantly related to the model were screened out using pRRophetic package. qPCR results showed that two model lncRNAs (USP2-AS1, NIFK-AS1) and three Cuproptosis genes (FDX1, PDHA1, DLAT) expressed differently between 10 pairs of breast cancer tissue samples and adjacent samples. Conclusion: The current study reveals that cuproptosis-related prognostic 2-lncRNAs signature (BCCuS) may be useful in predicting the prognosis, biological characteristics, and appropriate treatment of breast cancer patients.
RESUMO
Organophosphate esters (OPEs), known as novel alternative flame retardants, are a class of environmental endocrine disruptors. Long-term exposure to OPEs may bring a non-negligible health risk to human. Urinary OPE metabolites (mOPEs) are generally used as biomarkers to evaluate the internal exposure to OPEs. Diphenyl phosphate (DPHP), the main metabolite of aryl-OPEs, exhibited high detection rates and concentrations in urine samples. To establish a selective and simple analytical method for biomonitoring urinary DPHP, a specific magnetic molecular imprinted polymer (MMIP) was fabricated via a sol-gel method. Under optimum magnetic solid-phase extraction (MSPE) conditions, the resultant MMIP exhibited selective recognition ability, ideal adsorption capacity and good reusability on urinary DPHP enrichment. The developed MSPE method coupled with ultra-high performance liquid chromatography tandem mass spectrometry (U-HPLC-MS/MS) exhibited good precision and accuracy (spiked recoveries of 85.8%-109% with relative standard deviations (RSDs) ranged from 5.1%-13%), low detection limit of 0.035 ng/mL, and negligible matrix inhibition. Then we used this proposed method to detect urinary DPHP levels of recruited 30 college students and investigate the time variability and potential determinants. All urine samples revealed the presence of DPHP at a median concentration of 0.56 µg/g Creatinine (Cr). Moderate reproducibility of DPHP level was observed in first morning urine samples (ICC>0.40). Significant correlations were found between urinary DPHP levels and gender (ß=0.72; 95% CI: 0.48â¼0.96), sampling time (ß=0.36; 95% CI: 0.08â¼0.65) as well as the frequency for take-out food (ß=0.45; 95% CI: 0.07â¼0.74) (p< 0.05). Hence, a fast and sensitive MSPE-U-HPLC-MS/MS method was successfully built to quantify urinary DPHP.
Assuntos
Retardadores de Chama , Espectrometria de Massas em Tandem , Compostos de Bifenilo , Cromatografia Líquida de Alta Pressão/métodos , Retardadores de Chama/análise , Humanos , Fenômenos Magnéticos , Organofosfatos/urina , Fosfatos , Reprodutibilidade dos Testes , Extração em Fase Sólida , Estudantes , Espectrometria de Massas em Tandem/métodosRESUMO
Chemoresistance is closely related to the therapeutic effect and prognosis in breast cancer patients. Increasing evidences demonstrated that RNA binding proteins (RBPs) have notable roles in regulating cancer cell proliferation, metastasis and chemotherapeutic sensitivity. RNA binding motif single stranded interacting protein 2 (RBMS2), an RBP, has been considered to be a tumor suppressor in several cancers. However, its role of doxorubicin sensitivity in breast cancer patients has not yet been fully revealed. Here, we performed doxorubicin cytotoxicity assay, flow cytometry and mouse xenograft model to examine the influence of RBMS2 on doxorubicin sensitization in vitro and in vivo. RIP assay and dual-luciferase reporter assay were performed to explore the relationship between RBMS2 and BMF. Our data demonstrated that upregulation of RBMS2 in breast cancer cells could enhance sensitivity to doxorubicin and promote apoptosis in the presence of doxorubicin, while inhibition of RBMS2 showed an opposite trend. Moreover, this chemosensitizing effect of RBMS2 could be reversed by the inhibition of Bcl-2 modifying factor (BMF). RBMS2 positively regulated BMF expression and increased BMF-induced expression of (cleaved) caspase 3, (cleaved) caspase 9 and poly (ADP-Ribose) polymerase (PARP). These results uncovered a novel mechanism for RBMS2 in the sensibilization of doxorubicin, suggesting that RBMS2 may act as a potential therapeutic target for drug-resistant breast cancer.
Assuntos
Neoplasias da Mama , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genes Supressores de Tumor , Humanos , Camundongos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/metabolismoRESUMO
BACKGROUND: We performed this meta-analysis to provide a comprehensive evaluation of the role of MicroRNA-210 (miR-210) expression on the overall survival (OS) rate of cancers. METHODS: We searched for relevant available literatures on miR-210 and cancer until November 1st, 2016 on the databases PubMed, EMBASE, Cochrane Library, and Science Direct database. We calculated the pooled hazard ratio (HR) with 95% confidence intervals (CIs) for OS, which compared the high and low expression levels of miR-210 in patients of the available studies. Subgroup analysis was performed to evaluate the specific role of miR-210 in ethnicity and the type of cancers. Publication bias was evaluated using Begg funnel plots and Egger regression test. RESULTS: Overall, 19 studies were involved in this meta-analysis. The result indicated that upregulated miR-210 might be associated with poor OS outcome in various carcinomas, with the pooled HR of 1.80 (95% CI: 1.29-2.51). When stratified by disease, significant results were detected in breast cancer (HRâ=â2.67, 95% CI: 1.24-5.76) and glioma (HRâ=â2.42, 95% CI: 1.32-4.43). Besides, in the subgroup analysis by ethnicity, significant results were detected only in Asian populations (HRâ=â2.14, 95% CI: 1.37-3.34). CONCLUSION: The present meta-analysis suggests that high expressed miR-210 is significantly associated with OS in cancer patients, which has the potential to be a prognostic marker in cancers.