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1.
J Hazard Mater ; 422: 126963, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449333

RESUMO

Epidemiological evidence regarded the relations of phthalates with children's renal function and its underlying mechanism were largely unknown. We conducted a panel study using 287 paired urine-blood samples by repeated measurements of 103 children (4-13 years) across 3 seasons to explore effects of urinary phthalate metabolites on estimated glomerular filtration rate (eGFR) and the potential role of multiple cytokines. We found that mono-ethyl phthalate (MEP), monobutyl phthalate (MBP), mono-benzyl phthalate (MBzP) and mono-n-octyl phthalate (MOP) were significantly associated with eGFR reduction. Compared with the lowest quartile, MBP, MBzP and MEP in the third and fourth quartiles exhibited a graded decrease in eGFR. Meanwhile, weighted quantile sum regression analyses showed an inverse association of metabolites mixture with eGFR, to which MEP, MBzP, MOP were the major contributors. MEP also remained robust in multiple-phthalate model. Age and weight status might modify such relationships with significant interactions. Furthermore, eGFR related phthalate metabolites were associated with increased multiple cytokines, and CCL27, CXCL1 might be potential mediators between MEP and eGFR with mild mediated proportions. Accordingly, urinary phthalate metabolites were related to eGFR reduction in dose-response manner and multiple cytokines elevation, of which CCL27 and CXCL1 might partly mediate phthalate-associated decreased renal function among children.

2.
Front Oncol ; 11: 771579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858850

RESUMO

Adrenocortical carcinoma (ACC) is a rare malignant neoplasm that is prone to local invasion and metastasis. Meanwhile, overexpressed endothelial cell-specific molecule 1 (ESM1) is closely related to tumorigenesis of multitudinous tumors. However, the prognosis value and biological function of ESM1 in ACC remains undefined. In the current essay, the assessment in human ACC samples and multiple public cancer databases suggested that ESM1 was significantly overexpressed in ACC patients. The abnormal expression of ESM1 was evidently correlated with dismal overall survival (OS) in ACC patients. Then, the gene-set enrichment analysis (GSEA) was applied to unravel that ESM1 was mostly involved in cell cycle and Notch4 signaling pathway. Furthermore, in vitro experiment, RNA interference of ESM1 was carried out to state that ESM1 augments CDK1 and p21-mediated G2/M-phase transition of mitosis, cell proliferation via DLL4-Notch signaling pathway in human ACC cell line, SW13 cells. Additionally, two possible or available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored. Immune infiltration analysis highlighted that no significant difference was found in ACC patients between EMS1high and EMS1low group for immune checkpoint-related genes. In addition, the overexpression of ESM1 might trigger the accumulation of tumor mutation burden (TMB) during the cell cycle of DNA replication in ACC. The gene-drug interaction network then indicated that ESM1 inhibitors, such as cisplatin, might serve as potential drugs for the therapy of ACC. Collectively, the results asserted that ESM1 and related regulators might act as underlying prognostic biomarkers or novel therapeutic targets for ACC.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34773240

RESUMO

The antagonistic effect of selenium (Se) against cadmium (Cd)-induced breast carcinogenesis was reported, but underlying mechanisms were unclear. The aim of this study was to identify the epigenetically regulated genes and biological pathways mediating the antagonistic effect. We exposed MCF-7 cells to Cd and Se alone or simultaneously. Cell proliferation was assessed by MTT assay, and differential epigenome (DNA methylation, microRNA, and long non-coding RNA) was obtained by microarrays. We cross-verified the epigenetic markers with differential transcriptome, and the ones modulated by Cd and Se in opposite directions were regarded to mediate the antagonistic effect. The epigenetically regulated genes were validated by using gene expression data in human breast tissues. We further assessed the biological functions of these validated genes. Our results showed that Se alleviated the proliferative effect of Cd on MCF-7 cell. A total of 10 epigenetically regulated genes were regarded to mediate the antagonistic effect, including APBA2, KIAA0895, DHX35, CPEB3, SVIL, MYLK, ZFYVE28, ABLIM2, GRB10, and PCDH9. Biological function analyses suggested that these epigenetically regulated genes were involved in multiple cancer-related pathways, such as focal adhesion and PI3K/Akt pathway. In conclusion, we provided evidence that Se antagonized the Cd-induced breast carcinogenesis via epigenetic modification and revealed the critical pathways.

4.
Front Immunol ; 12: 749317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777361

RESUMO

Backgrounds: Takayasu arteritis (TAK) is a chronic, granulomatous vasculitis correlated with tuberculosis (TB). The two diseases share similar pathological characteristics and clinical manifestations which increase the difficulty to diagnose. Active tuberculosis (ATB) has implications for treatment strategies in TAK patients. Therefore, the investigation of clinical features and potential risk factors of ATB in TAK patients is vital. Methods: The study reviewed hospitalized patients diagnosed with TAK in our hospital from 2008, to 2021. TAK patients with ATB were enrolled as the case group. The control group was randomly selected in a 3:1 ratio. The clinical characteristics of TAK patients with and without ATB were compared. Multivariate logistic regression analysis was performed to determine risk factors for ATB in TAK patients. Results: We reviewed 1,789 patients and ultimately identified 30 (1.7%) ATB cases. TAK patients with ATB were more prone to develop symptoms including fever (p=0.001), fatigue (p=0.003), cough (p=0.037), expectoration (p<0.001), weight loss (p=0.003), and night sweating (p<0.001). Increased level of hypersensitive C reactive protein (hsCRP, p=0.001), decreased level of albumin (p=0.031), and higher positive rate of T-SPOT.TB test (p<0.001) were observed in the case group. Multivariate logistic regression analysis revealed that hsCRP >8 mg/L (OR 9.108; 95% CI, 1.096-75.711; p=0.041) and positive T-SPOT.TB result (OR 68.669; 95% CI, 7.291-646.738; p<0.001) were risk factors for ATB in TAK patients. The proportion of patients undergoing subsequent surgery for Takayasu arteritis was lower in patients with ATB (p<0.001). Conclusion: Our study suggested that the diagnosis of ATB should be considered when TAK patients experienced symptoms including fever, fatigue, weight loss, etc. hsCRP >8 mg/L and positive T-SPOT.TB result were identified as independent risk factors for ATB in TAK patients.

5.
Cornea ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34759200

RESUMO

PURPOSE: The purpose of this study was to assess the distribution and morphological variation of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects and patients with meibomian gland dysfunction (MGD) using laserscanningin vivo confocal microscopy. METHODS: A total of 34 healthy subjects and 32 patients with MGD were enrolled. All subjects underwent a conventional examination consisting of slitlamp biomicroscopy, tear film break-up time, and the Schirmer test. In vivo microscopy was applied to analyze the morphological changes in the diffuse lymphoid layer and lymphoid follicles in CALT. Conjunctival impression cytology (CIC) of samples of patients' palpebral conjunctiva and immunofluorescence staining of CD4 and CD8 antibodies were also performed to indicate the immune response status of CALT. RESULTS: In the MGD group, the density of diffuse lymphocytes (P < 0.001), follicles (P < 0.001), and perifollicular lymphocytes was higher (P < 0.001) and the central reflection of the follicles was stronger (P < 0.001) than in the control group, while there was no difference in the follicle area (P = 0.758). Besides, diffuse lymphocyte density was correlated with telangiectasia, and follicular center reflection intensity was correlated with plugging. CIC immunofluorescence staining showed a higher percentage of CD4+ (P < 0.001) and CD8+ (P < 0.001) cells in the MGD group than in the control group. CONCLUSIONS: Using laser scanning in vivo confocal microscopy and CIC immunofluorescence staining, we observed the activation of CALT in patients with MGD, and some CALT-related parameters correlated with the lid margin findings of patients with MGD.

6.
Front Oncol ; 11: 726671, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760693

RESUMO

Clear cell renal cell carcinoma (ccRCC) carrying wild-type Von Hippel-Lindau (VHL) tumor suppressor are more invasive and of high morbidity. Concurrently, competing endogenous RNA (ceRNA) network has been suggested to play an important role in ccRCC malignancy. In order to understand why the patients carrying wild-type VHL gene have high degrees of invasion and morbidity, we applied bioinformatics approaches to identify 861 differentially expressed RNAs (DE-RNAs) between patients carrying wild-type and patients carrying mutant VHL from The Cancer Genome Atlas (TCGA) database, established a ceRNA network including 122 RNAs, and elected six survival-related DE-RNAs including Linc00942, Linc00858, RP13_392I16.1, hsa-miR-182-5p, hsa-miR-183-5p, and PAX3. Examining clinical samples from our hospital revealed that patients carrying wild-type VHL had significantly higher levels of all six RNAs than those carrying mutant VHL. Patients carrying wild-type VHL had significantly higher risk scores, which were calculated based on expression levels of all six RNAs, than those carrying mutant VHL. Patients with higher risk scores had significantly shorter survival times than those with lower risk scores. Therefore, the risk scores serve well to predict malignancy and prognosis.

7.
Front Pharmacol ; 12: 765790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733164

RESUMO

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

8.
Int Med Case Rep J ; 14: 765-771, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803407

RESUMO

Background: Bladder paraganglioma (BPG) is one of the rare neuroendocrine neoplasms that develops from neural crest cells. It categorizes into functional and non-functional types based on the catecholamines secretion. Currently, functional BPG is predicted in advance based on signs and symptoms of catecholamine excess, such as hypertension and "micturition attacks". However, it is often overlooked because of its rareness. Misdiagnosis of a functional tumor may increase the risk of surgical intervention. Case Presentation: We reported 3 cases of BPG that they were admitted to the hospital due to abdominal pain or gross hematuria. Computed tomography (CT) scans showed space-occupying lesions in the bladders with diameters less than 3cm. There were no typical catecholamine excess symptoms before surgical intervention. Postoperative pathology confirmed BPG after removal of the tumor. We also analyze 69 cases of BPG that has been reported and found that 78.0% cases were functional among the tumors larger than 3cm. Conclusion: Bladder tumors larger than 3cm in diameter can serve as an additional predictor of functional BPG. Patients who are suspected should undergo magnetic resonance imaging (MRI) scans, 123/131 metaiodobenzylguanidine (MIBG) scan, and have their catecholamine levels tested. Once the diagnosis is confirmed, patients should be started on fluid replacement therapy and adrenergic blockade to abate the disorders associated with catecholamine excess.

9.
Infect Drug Resist ; 14: 4689-4697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785916

RESUMO

Background: The antimicrobial activities of some new oxazolidinones against slowly growing mycobacteria (SGM) have never been well evaluated. Methods: We evaluate the in vitro susceptibility of 20 reference strains and 157 clinical isolates, pertaining different SGM species, against four oxazolidinones, ie, delpazolid, sutezolid, tedizolid and linezolid. In addition, the association of linezolid resistance and mutations in 23srRNA, rplC, rplD were also tested. Results: Sutezolid presented the strongest antimicrobial activity against the clinical isolates of M. intracellulare than the other oxazolidinones, with MIC50 at 2 µg/mL and MIC90 at 4 µg/mL. MICs of sutezolid were usually 4- to 8-fold lower than these of linezolid against M. intracellulare and M. avium. The tested isolates of M. kansasii were susceptible to all of the four oxazolidinones. According to the multiple sequence alignment, novel 23srRNA mutations (A2267C and A2266G) in M. intracellulare and rplD mutations (Thr147Ala) in M. avium were identified in this study which have plausible involvement in rendering resistance against linezolid. Conclusion: This study showed that sutezolid harbors the strongest inhibitory activity against M. intracellulare, M. avium and M. kansasii in vitro, which provided important insights on the potential clinical application of oxazolidinones for treating SGM infections.

10.
Adv Mater ; : e2107420, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845763

RESUMO

A prerequisite for commercializing perovskite photovoltaics is to develop a swift and eco-friendly synthesis route, which guarantees the mass production of halide perovskites in the industry. Herein, a green-solvent-assisted mechanochemical strategy is developed for fast synthesizing a stoichiometric δ-phase formamidinium lead iodide (δ-FAPbI3 ) powder, which serves as a high-purity precursor for perovskite films deposition with low defects. The pre-synthesized δ-FAPbI3 precursor possesses high concentration of micron-sized colloids, which are in favor of preferable crystallization by spontaneous nucleation. The resultant perovskite films own preferred crystal orientations of cubic (100) plane, which is beneficial for superior carrier transport compared to that of the films with isotropic crystal orientations using "mixture of PbI2 and FAI" as precursors. As a result, high-performance perovskite solar cells with a maximum power conversion efficiency of 24.2% are obtained. Moreover, the δ-FAPbI3 powder shows superior storage stability for more than ten months in ambient environment (40 ± 10% relative humidity), being conducive to a facile and practical storage for further commercialization. This article is protected by copyright. All rights reserved.

11.
Pathol Oncol Res ; 27: 1609967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840533

RESUMO

SLC13A4 is a sodium sulfate co-transporter, which is expressed in brains, placentas, thymes and other tissues, plays an essential role in maintaining the metabolic balance of sulfate in vivo. The TCGA database shows that it is differentially expressed in a variety of tumors, but its prognostic value in tumors has not been clarified. TCGA, Oncomine and Timer databases were used to analyze SLC13A4 mRNA expression in cancer tissues and normal tissues, and its correlation with clinical prognosis in head and neck tumor. The CIBERSORT database was used to analyze the correlation between SLC13A4 expression and the infiltration of immune cells. SLC13A4 enrichment analysis was carried out by GSEA. SLC13A4 mRNA levels were significantly lower in head and neck tumors than in paracancer tissues. SLC13A4 expression in Head and neck squamous cell carcinoma (HNSCC) was closely related to tumor pathological grade and clinical stage. Decreased SLC13A4 expression was associated with poor overall survival (OS), progression free survival (PFS), disease specific survival (DSS) and recurrence free survival (RFS) in HNSCC patients. The expression of SLC13A4 was negatively correlated with Monocytes, M1 macrophages, M2 macrophages, resting CD4+ memory T cells, resting NK cells and activated NK cells, but positively correlated with neutrophils, plasma cells, T follicular helper cells, gamma delta T cells, regulatory T cells and naive B cells. In addition, the genes in SLC13A4 low-expression group were mainly concentrated in immunity-related activities, viral diseases, typical tumor pathways and metabolism. The SLC13A4 high expression group was mainly enriched in metabolic pathways. These suggest that SLC13A4 may be a potential prognostic biomarker in HNSC and correlated with immune infiltrates.

12.
Aging (Albany NY) ; 13(20): 23620-23636, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34644262

RESUMO

Amyloid-ß (Aß) accumulating is considered as a causative factor for formation of senile plaque in Alzheimer's disease (AD), but its mechanism is still elusive. The Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2), a key redox cofactor for energy metabolism, is reduced in AD. Accumulative evidence has shown that the decrease of α-secretase activity, a disintegrin and metalloprotease domain 10 (ADAM10), is responsible for the increase of Aß productions in AD patient's brain. Here, we observe that the activity of α-secretase ADAM10 and levels of Nmnat2 are significantly decreased, meanwhile there is a simultaneous elevation of Aß in Tg2576 mice. Over-expression of Nmnat2 increases the mRNA expression of α-secretase ADAM10 and its activity and inhibits Aß production in N2a/APPswe cells, which can be abolished by Compound C, an AMPK antagonist, suggesting that AMPK is involved in over-expression of Nmnat2 against Aß production. The further assays demonstrate that Nmnat2 activates AMPK by up-regulating the ratio of NAD+/NADH, moreover AMPK agonist AICAR can also increase ADAM10 activity and reduces Aß1-40/1-42. Taken together, Nmnat2 suppresses Aß production and up-regulates ADAM10 in AMPK activity-dependent manner, suggesting that Nmnat2 may serve as a new potential target in arresting AD.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34657238

RESUMO

Clinical trials in patients with ulcerative colitis (UC) face the challenge of high and variable placebo response rates. The Mayo Clinical Score (MCS) is used widely as the primary endpoint in clinical trials to describe the clinical status of patients with UC. The MCS is comprised of four subscores, each scored 0, 1, 2 and 3: rectal bleeding (RB), stool frequency (SF), physician's global assessment (PGA), and endoscopy (ENDO) subscore. Excluding the PGA subscore gives the modified MCS. Quantitative insight on the placebo response, and its impact on the components of the MCS over time, can better inform clinical trial design and interpretation. Longitudinal modeling of the MCS, and the modified MCS, can be challenging due to complex clinical trial design, population heterogeneity, and limited assessments for the ENDO subscore. The current study pooled patient-level placebo/standard of care (SoC) arm data from five clinical trials in the TransCelerate database to develop a longitudinal placebo response model that describes the MCS over time in patients with UC. MCS subscores were modeled using proportional odds models, and the removal of patients from the placebo/SoC arm, or "dropout", was modeled using logistic regression models. The subscore and dropout models were linked to allow for the prediction of the MCS and the modified MCS. Stepwise covariate modeling identified prior exposure to TNF-α antagonists as a statistically significant predictor on the RB + SF subscore. Patients with prior exposure to TNF-α antagonists had higher post-baseline RB + SF subscores than naive patients.

15.
Bioinformatics ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664633

RESUMO

MOTIVATION: Medical image fusion has developed into an important technology, which can effectively merge the significant information of multiple source images into one image. Fused images with abundant and complementary information are desirable, which contributes to clinical diagnosis and surgical planning. RESULTS: In this paper, the concept of the skewness of pixel intensity (SPI) and a novel adaptive co-occurrence filter (ACOF) based image decomposition optimization model are proposed to improve the quality of fused images. Experimental results demonstrate that the proposed method outperforms 22 state-of-the-art medical image fusion methods in terms of five objective indices and subjective evaluation, and it has higher computational efficiency. AVAILABILITY AND IMPLEMENTATION: First, the concept of SPI is applied to the co-occurrence filter to design ACOF. The initial base layers of source images are obtained using ACOF, which relies on the contents of images rather than fixed scale. Then, the widely used iterative filter framework is replaced with an optimization model to ensure that the base layer and detail layer are sufficiently separated and the image decomposition has higher computational efficiency. The optimization function is constructed based on the characteristics of the ideal base layer. Finally, the fused images are generated by designed fusion rules and linear addition. The code and data can be downloaded at https://github.com/zhunui/acof. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

16.
Exp Gerontol ; 155: 111576, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34597711

RESUMO

OBJECTIVE: To evaluate the predict value of serum/urocystatin C in acute kidney injury (AKI) in elderly patients with sepsis. METHODS: A retrospective study was performed and 80 senile patients with sepsis in ** hospital of China was included. According to the diagnosis of AKI, all patients were divided into non-AKI group and AKI group. The clinical characteristics, laboratory and physiological indicators of the two groups were compared. The receiver operating characteristic curve (ROC) was used to analyze the accuracy of the variables, including serum cystatin C, urocystatin C, and serum creatinine, to predict the occurrence of AKI in patients with sepsis. RESULTS: Of the 80 elderly patients with sepsis in China, 29 patients had AKI. Compared with the non-AKI group, patients in the AKI group had higher APACHE II scores, higher SOFA scores, higher procalcitonin, and lower mean arterial pressure (P < 0.05). The levels of serum cystatin C, urocystatin C, and serum creatinine in the AKI group were significantly higher than those in the non-AKI group (P < 0.05), while the difference in intensive care unit (ICU) mortality rate between the two groups was not significantly different (P > 0.05). The ROC curve showed that the area under the curve of serum cystatin C was 0.893, the area under the curve of urocystatin C was 0.898, and the area under the curve of serum creatinine was 0.652. CONCLUSION: Serum cystatin and urocystatin could be used to predict the occurrence of AKI in elderly patients with sepsis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34695267

RESUMO

OBJECTIVE: Elder abuse (EA) is a critical social, health, and economic issue worldwide. To date, there is limited information on EA in certain similar culture-specific subpopulations, especially in East Asia. This study aims to summarize EA incidence in East Asia through a systematic review and meta-analysis and identify its variations and heterogeneity in the incidence estimates. METHODS/DESIGN: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol. Systematic review registration number PROSPERO CRD42020197131. A systematic literature search was performed to identify relevant articles published before July 5th, 2020, from six electronic databases. Two reviewers screened for relevance of the studies against eligible criteria and assessed the bias of the included studies independently. A random-effect model was adopted to estimate the incidence of EA, followed by subgroup analyses and multi meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analysis by Stata version 15.1. RESULTS: Twelve eligible studies were included in the meta-analysis, which involved 79,395 subjects from 3 East Asian countries (China, Japan, and South Korea) ranging from 2004 to 2020. The overall incidence of EA was 78.33 per 1000 person-year (95% CI: 39.12-156.87) with high between-study variability (χ2  = 15,568, d.f. = 11, p<0.001; I2  = 99.9%). The sampling method, sample size, scope, instrument, data collection method, income classification, types of participants, and urbanity are all the sources of heterogeneity, which can explain nearly 100% of the variance between studies. CONCLUSIONS: The incidence of EA in this study is not as high as the global level. It may be furtherly underestimated in East Asia due to cultural norms. It is imperative to develop a culture-tailored EA assessment instrument to evaluate potential victims. Future studies should also identify more effective educational programs to raise the public's awareness and promote recognition ability.

18.
J Cancer ; 12(21): 6507-6518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659542

RESUMO

Purpose: Considerable variations in methylation profile have been found in various cancers to modulate tumorigenesis and affect prognosis. To provide a theoretical basis for early detection, prognosis evaluation and targeted treatment for patients with pancreatic ductal adenocarcinoma: PDAC, this study identified methylation-driven genes in PDAC and explored their prognostic performance. Methods: The methylation, expression and clinical data of PDAC patients were extracted from TCGA database. Based on the ß-mixture model of the MethylMix R package, the differential methylation status and connection between methylation and expression degree were examined to screen out methylation-driven genes in PDAC. COX analyses and lasso regressions were applied to construct a linear risk model based on methylation-driven genes. Univariate and multivariate analyses were performed to ensure the risk model was an independent prognostic factor. Joint survival analyses of methylation and gene expression were conducted to explore the prognostic value of component genes. The methylation sites in the key genes were also investigated. Results: A total of 118 methylation-driven genes in PDAC were identified, and two genes (FOXI2, MYEOV) constituted the risk model whose AUC was 0.722 at one year of overall survival rate, displaying a better performance on survival prediction than other clinical features. Further survival analyses demonstrated that the expression of MYEOV and combined methylation and expression levels of the genes MYEOV and FOXI2 can be potential biomarkers for survival prediction and targets of drug manipulation of PDAC patients. Close relationships were discovered between two sites in MYEOV and one site in FOXI2 and the prognosis of PDAC patients. Conclusion: Concentrating on DNA methylation, our study identified potential biomarkers and developed a reliable short-term predictive model for prognosis of PDAC patients.

19.
Front Cell Dev Biol ; 9: 728242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708039

RESUMO

Background: Spinal cord injury (SCI) is a severe neurological deficit affecting both young and older people worldwide. The potential role of key enhancer RNAs (eRNAs) in SCI remains elusive, which is a prominent challenge in the trauma repair process. This study aims to investigate the roles of key eRNAs, transcription factors (TFs), signaling pathways, and small-molecule inhibitors in SCI using multi-omics bioinformatics analysis. Methods: Microarray data of peripheral blood mononuclear cell (PBMC) samples from 27 healthy volunteers and 25 chronic-phase SCI patients were retrieved from the Gene Expression Omnibus database. Differentially expressed transcription factors (DETFs), differentially expressed enhancer RNAs (DEeRNAs), and differentially expressed target genes (DETGs) were identified using the Linear Models for Microarray Data (limma) package. Fraction of immune cells was estimated using CIBERSORT algorithm. Gene Set Variation Analysis (GSVA) was applied to identify the downstream signaling pathways. The eRNA regulatory network was constructed based on the correlation results. Connectivity Map (CMap) database was used to find potential drugs for SCI patients. The cellular communication analysis was performed to explore the molecular regulation mechanism of SCI based on single-cell RNA sequencing (scRNA-seq) data. Chromatin immunoprecipitation sequencing (ChIP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data were used to validate the key regulatory mechanisms. scRNA-seq dataset was used to validate the cell subtype localization of the key eRNAs. Results: In total, 21 DETFs, 24 DEeRNAs, and 829 DETGs were identified. A regulatory network of 13 DETFs, six DEeRNAs, seven DETGs, two hallmark pathways, two immune cells, and six immune pathways was constructed. The link of Splicing factor proline and glutamine rich (SFPQ) (TF) and vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) (eRNA) (R = 0.990, p < 0.001, positive), VOPP1 (eRNA) and epidermal growth factor receptor (EGFR) (target gene) (R = 0.974, p < 0.001, positive), VOPP1, and T helper (Th) cells (R = -0.987, p < 0.001, negative), and VOPP1 and hallmark coagulation (R = 0.937, p < 0.001, positive) was selected. Trichostatin A was considered the best compound target to SCI-related eRNAs (specificity = 0.471, p < 0.001). Conclusion: VOPP1, upregulated by SFPQ, strengthened the transient expression of EGFR. Th cells and coagulation were the potential downstream pathways of VOPP1. This regulatory network and potential inhibitors provide novel diagnostic biomarkers and therapeutic targets for SCI.

20.
Sci Rep ; 11(1): 21014, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697393

RESUMO

Cisplatin (CDDP) based chemotherapy is widely used as the first-line strategy in treating non-small cell lung cancer (NSCLC), especially lung squamous cell carcinoma (LUSC). However, secondary cisplatin resistance majorly undermines the cisplatin efficacy leading to a worse prognosis. In this respect, we have identified the role of the DLX6-AS1/miR-181a-5p/miR-382-5p/CELF1 axis in regulating cisplatin resistance of LUSC. qRT-PCR and Western blot analysis were applied to detect gene expression. Transwell assay was used to evaluate the migration and invasion ability of LUSC cells. CCK-8 assay was used to investigate the IC50 of LUSC cells. Flow cytometry was used to test cell apoptosis rate. RNA pull-down and Dual luciferase reporter gene assay were performed to evaluate the crosstalk. DLX6-AS1 was aberrantly high expressed in LUSC tissues and cell lines, and negatively correlated with miR-181a-5p and miR-382-5p expression. DLX6-AS1 expression was enhanced by H3K4me1 in cisplatin resistant LUSC cells. Besides, DLX6-AS1 knockdown led to impaired IC50 of cisplatin resistant LUSC cells. Furthermore, DLX6-AS1 interacted with miR-181a-5p and miR-382-5p to regulate CELF1 expression and thereby mediated the cisplatin sensitivity of cisplatin resistant LUSC cells. DLX6-AS1 induced by H3K4me1 played an important role in promoting secondary cisplatin resistance of LUSC through regulating the miR-181a-5p/miR-382-5p/CELF1 axis. Therefore, targeting DLX6-AS1 might be a novel way of reversing secondary cisplatin resistance in LUSC.

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