Our study aimed to investigate whether CAF (cancer-associated fibroblasts) were involved in long noncoding RNAs (lncRNA)-regulated radioresponse in esophageal squamous cell carcinoma (ESCC).
By use ...of lncRNAs PCR array, 38 lncRNAs were screened in esophageal cancer cells and in normal esophageal epithelial cells Het-1A. LncRNA DNM3OS was detected in tumor tissues of patients with ESCC and in matched normal esophageal epithelial tissues by qRT-PCR analysis and
hybridization assay. The association of DNM3OS and tumor radioresistance was investigated
and
. The influences of DNM3OS on DNA damage response (DDR) was investigated by Western blotting, immunofluorescence imaging, and comet assay. The mechanisms by which CAFs promoted DNM3OS expression was investigated by kinase inhibitors' screening, luciferase assay, and chromatin immunoprecipitation.
Among the 38 lncRNAs tested, DNM3OS was found to have a much higher expression level in esophageal cancer cells than in Het-1A. In tumor tissues of 16 patients with ESCC, the expression level of DNM3OS showed an average increase of 6.3429-fold compared with that in matched normal tissues. DNM3OS conferred significant radioresistance
and
by regulating DDR. CAFs promoted the expression of DNM3OS with a 39.2554-fold and 38.3163-fold increase in KYSE-30 and KYSE-140, respectively. CAFs promoted the expression of DNM3OS in a PDGFβ/PDGFRβ/FOXO1 signaling pathway-dependent manner. FOXO1, a transcription factor downstream of PDGFβ/PDGFRβ signaling pathway, initiated the transcription of DNM3OS by binding to DNM3OS promoter.
Our study highlighted CAF-promoted DNM3OS as an attractive target to reverse tumor radioresistance in ESCC.
In genome-wide association study, extracting disease-associated genetic variants among millions of single nucleotide polymorphisms is of great importance. When the response is a binary variable, the ...Cochran-Armitage trend tests and associated MAX test are among the most widely used methods for association analysis. However, the theoretical guarantees for applying these methods to variable screening have not been built. To fill this gap, we propose screening procedures based on adjusted versions of these methods and prove their sure screening properties and ranking consistency properties. Extensive simulations are conducted to compare the performances of different screening procedures and demonstrate the robustness and efficiency of MAX test-based screening procedure. A case study on a dataset of type 1 diabetes further verifies their effectiveness.
Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major ...component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS accumulation following radiation, by which DNA damage repair was enhanced and the radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells induced CXCL1 expression in an autocrine/paracrine signaling loop, which further enhanced tumor radioresistance. Together, our study highlighted CAF-secreted CXCL1 as an attractive target to reverse tumor radioresistance and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy.
Eddy current is a magnetic field effect generated in alternating magnetic field (AMF), which could trigger continuous local heating, reducing the energy consumption without impairing the life of the ...catalyst or reactor. Unfortunately, the investigation of eddy current effect on transition metal disulfides (TMDs) electrocatalysis is still in its infancy, and its actual electrocatalytic applications has been impeded by the multilayered structure of traditional layered TMDs. Typically, the step pyramid MoS2, with a layer‐by‐layer stacking structure just like the silicon steel plate in the transformer, showing an inevitable interlayer potential barrier will suppress the generation of eddy current and cause low efficiency of magnetic heating. In this work, the designed screw pyramid MoS2 can facilitate the formation of micro eddy current and maximize utilization of magnetic heating to boost electrocatalytic activity, benefiting from its eliminated interlayer potential barrier. This work provides a new thinking for the design of field‐assisted electrocatalytic reactions and development of the advanced catalyst technology.
The screw pyramid MoS2 with abundant edge active sites and eliminated interlayer potential barrier can facilitate the formation of micro eddy current and efficiently utilize magnetic heating to boost electrocatalytic activity under alternating magnetic field. It provides a new strategy for further improvement of electrocatalytic performance and advanced catalyst technology.
Cytochrome P450 2C9 (CYP2C9) is involved in the metabolism of cancer drugs and exogenous carcinogens. In our study, CYP2C9 was downregulated in multiple cohorts of human esophageal squamous cell ...carcinoma (ESCC). Until now, its role and epigenetic regulation of CYP2C9 repression in ESCC remain poorly understood. CYP2C9 repression in collected ESCC patient tumor tissues was demonstrated by RT-qPCR and Western blot. The histone acetylation level was carried out by the treatment of histone deacetylase inhibitor TSA and RNA interference. Epigenetic analysis revealed that the increased expression of CYP2C9 in KYSE-150 and TE1 cells was characterized by inhibition of HDAC8 and HDAC1, respectively. TSA decreased the levels of HDAC occupancy around CYP2C9 promoter region greatly. Overexpression of CYP2C9 reduced the invasion and migration of ESCC cells.
Advances in biologic technology enable researchers to obtain a huge amount of genetic and genomic data, whose dimensions are often quite high on both phenotypes and variants. Testing their ...association with multiple phenotypes has been a hot topic in recent years. Traditional single phenotype multiple variant analysis has to be adjusted for multiple testing and thus suffers from substantial power loss due to ignorance of correlation across phenotypes. Similarity-based method, which uses the trace of product of two similarity matrices as a test statistic, has emerged as a useful tool to handle this problem. However, it loses power when the correlation strength within multiple phenotypes is middle or strong, for some signals represented by the eigenvalues of phenotypic similarity matrix are masked by others. We propose a divided-and-combined omnibus test to handle this drawback of the similarity-based method. Based on the divided-and-combined strategy, we first divide signals into two groups in a series of cut points according to eigenvalues of the phenotypic similarity matrix and combine analysis results via the Cauchy-combined method to reach a final statistic. Extensive simulations and application to a pig data demonstrate that the proposed statistic is much more powerful and robust than the original test under most of the considered scenarios, and sometimes the power increase can be more than 0.6. Divided-and-combined omnibus test facilitates genetic association analysis with high-dimensional data and achieves much higher power than the existing similarity based method. In fact, divided-and-combined omnibus test can be used whenever the association analysis between two multivariate variables needs to be conducted.
Chronic wounds caused by severe trauma remain a serious challenge for clinical treatment. In this study, we developed a novel angiogenic 3D-bioprinted peptide patch to improve skin wound healing. The ...3D-bioprinted technology can fabricate individual patches according to the shape characteristics of the damaged tissue. Gelatin methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) have excellent biocompatibility and biodegradability, and were used as a biomaterial to produce bioprinted patches. The pro-angiogenic QHREDGS peptide was covalently conjugated to the 3D-bioprinted GelMA/HAMA patches, extending the release of QHREDGS and improving the angiogenic properties of the patch. Our results demonstrated that these 3D-bioprinted peptide patches showed excellent biocompatibility, angiogenesis, and tissue repair both in vivo and in vitro. These findings indicated that 3D-bioprinted peptide patches improved skin wound healing and could be used in other tissue engineering applications.
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Multiple response regression model is commonly employed to investigate the relationship between multiple outcomes and a set of potential predictors, where single-response analysis and multivariate ...analysis of variance (MANOVA) are two frequently used methods for association analysis. However, both methods have their own limitations. The basis of the former method is independence of multiple responses and the latter one assumes that multiple responses are normally distributed. In this work, the authors propose a test statistic for multiple response association analysis in high-dimensional situations based on
F
statistic. It is free of normal distribution assumption and the asymptotic normal distribution is obtained under some regular conditions. Extensive computer simulations and four real data applications show its superiority over single-response analysis and MANOVA methods.
Aims/Introduction
Long non‐coding RNAs (lncRNAs) exert essential functions in the pathogenesis of diabetic nephropathy (DN). LncRNA T‐cell factor 7 (TCF7) and semaphorin‐3A (SEMA3A) have been found ...to be involved in the progression of diabetic nephropathy. However, whether the effect of TCF7 on the pathogenesis of diabetic nephropathy is mediated by SEMA3A remains unclear.
Materials and Methods
TCF7, miR‐16‐5p, and SEMA3A were quantified by a qRT‐PCR or immunoblotting method. A CCK‐8 assay gauged the cell viability. Measurement of cell apoptosis was done using flow cytometry. RNA immunoprecipitation (RIP), dual‐luciferase reporter, and RNA pull‐down assays were utilized to assay the targeted interactions among the variables.
Results
The TCF7 and SEMA3A levels were elevated in serum from patients with diabetic nephropathy. TCF7 silencing or SEMA3A depletion ameliorated high glucose (HG)‐induced podocyte injury. Moreover, TCF7 silencing protected against HG‐induced podocyte injury by down‐regulating SEMA3A. TCF7 targeted miR‐16‐5p, and miR‐16‐5p targeted SEMA3A. Furthermore, TCF7 affected the expression of SEMA3A by competing specifically for shared miR‐16‐5p.
Conclusions
These findings suggested that TCF7 silencing attenuated high glucose‐induced podocyte damage partially through the miR‐16‐5p/SEMA3A regulation cascade.
our current work indicated that the silencing of TCF7 attenuated HG‐induced injury in human podocytes at least in part through regulating SEMA3A expression via sponging miR‐16‐5p. These findings provided a new insight into the molecular mechanism for HG‐induced podocyte damage.
The purpose of this study was to examine the current state of the application of imaging in sleep research in degenerative disease, as well as hotspots and trends.
A search was conducted on the Web ...of Science Core Collection (WoSCC) between 1 September 2012, and 31 August 2022 for literature related to sleep imaging. This study analyzed 7,679 articles published in this field over the past 10 years, using CiteSpace to analyze tendencies, countries, institutions, authors, and hotspots.
There were 7,679 articles on the application of imaging to sleep research published by 566 institutions located in 135 countries in 1,428 journals; the number of articles was increasing on a yearly basis. According to keyword analysis, the research direction of the application of imaging in sleep research focused on the effects of degenerative diseases on sleep, such as Parkinson's disease, Alzheimer's disease, and small vessel disease. A literature evaluation found that Parkinson's disease, insomnia, sleep quality, and rapid eye movement sleep behavior disorder were the top research trends in this field.
A growing body of research has focused on sleep disorders caused by degenerative diseases. In the application of imaging to sleep research, magnetic resonance functional brain imaging represents a reliable research method. In the future, more aging-related diseases may be the subject of sleep-related research, and imaging could provide convenient and reliable evidence in this respect.
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