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Conductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair. Herein, we report a miniature self-powered biomimetic trinity triboelectric nanogenerator with a unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis in one cardiac patch. Trinity triboelectric nanogenerator conductive cardiac patches improve the electroactivity of the infarcted heart and can also wirelessly monitor electrocardiosignal to a mobile device for diagnosis. RNA sequencing analysis from rat hearts reveals that this trinity cardiac patches mainly regulates cardiac muscle contraction-, energy metabolism-, and vascular regulation-related mRNA expressions in vivo. The research is spawning a device that truly integrates an electrical stimulation of a functional heart patch and self-powered e-care remote diagnostic sensor. Infarted myocardium hampers the synchronous electroactivity of the cardiac tissue. Here, the authors showcase a battery-free conductive cardiac patch made of reduced graphene and its therapeutic efficacy for cardiac repair. [ABSTRACT FROM AUTHOR]

Lipoxin A4 (LXA4) has been identified as the braking signal of inflammation, but the specific role of LXA4 in regulating the regenerative potential of periodontal ligament stem cells (PDLSCs) remains unclear. The aim of this study was to investigate whether and, if so, how LXA4 improves the osteogenic differentiation of PDLSCs in a lipopolysaccharide (LPS)‐induced inflammatory environment. We detected the effects of LXA4 on the osteogenic differentiation of PDLSCs in vitro and explored the bone regenerative potential of LXA4‐treated inflammatory PDLSCs in vivo using a calvarial critical sized defect model in male rats. RNA sequencing, real‐time PCR and western blot were performed to elucidate the relevant potential mechanisms. Results showed that LXA4 promoted the proliferation, migration and osteogenic differentiation of PDLSCs in vitro, and effectively improved the impaired osteogenic capacity of PDLSCs induced by LPS both in vitro and in vivo. Mechanistically, LXA4 significantly promoted the PI3K/AKT phosphorylation under inflammatory conditions. Additionally, LY294002 (a PI3K inhibitor) blocked the effect of LXA4, suggesting that the PI3K/AKT pathway is a key signaling pathway that mediates the effect of LXA4 on the osteogenesis of inflammatory PDLSCs. These findings indicate LXA4 may be a promising strategy for periodontal regeneration using inflammatory PDLSCs. [ABSTRACT FROM AUTHOR]

MicroRNAs play key regulatory roles in plant development. The changed pattern of miRNA expression is involved in the production of viral symptoms. Here, we showed that a small RNA, Seq119, a putative novel microRNA, is associated with the low seed setting rate, a viral symptom of rice stripe virus (RSV)-infected rice. The expression of Seq 119 was downregulated in RSV-infected rice. The overexpression of Seq119 in transgenic rice plants did not cause any obvious phenotypic changes in plant development. When the expression of Seq119 was suppressed in rice plants either by expressing a mimic target or by CRISPR/Cas editing, seed setting rates were extremely low, similar to the effects of RSV infection. The putative targets of Seq119 were then predicted. The overexpression of the target of Seq119 in rice caused a low seed setting rate, similar to that in Seq119-suppressed or edited rice plants. Consistently, the expression of the target was upregulated in Seq119-suppressed and edited rice plants. These results suggest that downregulated Seq119 is associated with the low seed setting rate symptom of the RSV in rice. [ABSTRACT FROM AUTHOR]

Genetic variation is considered to affect the N6‐methyladenosine (m6A) RNA transcript modification, which is the most prevalent posttranscriptional messenger RNA modification. This study aimed to identify m6A‐associated single‐nucleotide polymorphisms (m6A‐SNPs) that may affect m6A methylation from numerous periodontitis (PD) SNPs. We identified an abundance of m6A‐SNPs by analyzing raw data of published PD genome‐wide association studies and m6A‐SNPs list from the m6AVar database. Other evidence was found in public databases for expression quantitative trait loci (eQTL) and differential gene expression analysis. Accordingly, 1938 m6A‐SNPs were identified, 104 of which appeared to be associated with PD (p < .05) while 65 showed eQTL signals. Lastly, the leading SNP rs2723183 (p = 3.93E−07) was predicted to regulate local gene IL‐37 expression in PD (p = 2.64E−05; in GSE10334) and change regulatory motif RXRA. In summary, dozens of PD‐associated m6A‐SNPs were identified and their possible functions were demonstrated in this study. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. The discovery of prognostic biomarkers is still one of the major challenges to improve clinical treatment of BC patients. In order to assist biologists and clinicians in easily evaluating the prognostic potency of genes in BC patients, we developed a user-friendly Online consensus Survival tool for bladder cancer (OSblca), to analyze the prognostic value of genes. The OSblca includes gene expression profiles of 1,075 BC patients and their respective clinical follow-up information. The clinical follow-up data include overall survival (OS), disease specific survival (DSS), disease free interval (DFI), and progression free interval (PFI). To analyze the prognostic value of a gene, users only need to input the official gene symbol and then click the "Kaplan-Meier plot" button, and Kaplan-Meier curve with the hazard ratio, 95% confidence intervals and log-rank P -value are generated and graphically displayed on the website using default options. For advanced analysis, users could limit their analysis by confounding factors including data source, survival type, TNM stage, histological type, smoking history, gender, lymph invasion, and race, which are set up as optional parameters to meet the specific needs of different researchers. To test the performance of the web server, we have tested and validated its reliability using previously reported prognostic biomarkers, including KPNA2, TP53 , and MYC etc., which had their prognostic values validated as reported in OSblca. In conclusion, OSblca is a useful tool to evaluate and discover novel prognostic biomarkers in BC. The web server can be accessed at http://bioinfo.henu.edu.cn/BLCA/BLCAList.jsp. [ABSTRACT FROM AUTHOR]

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Lipotransfer has been applied in breast augmentation surgery for several years and the resident adipose-derived stem cells (ASCs) play an important role in enhancing fat graft survival. However, the interaction between ASCs and mammary epithelium is not fully understood. Many studies have shown that ASCs have a tumor-supportive effect in breast cancer. To the best of our knowledge, this is the first study on the effect of mammary epithelial cells on the human ASCs in 3D culture. ASCs were cultivated on matrigel in the conditioned medium (CM) prepared from a human breast epithelial cell line (HBL-100). The ASCs formed KRT18-positive acini-like structures after stimulation with breast epithelial cells. The expression of epithelial genes (CDH1 and KRT18) was up-regulated while the expression of mesenchymal specific genes (CDH2 and VIM) was down-regulated as determined by qRT-PCR. The stemness marker (CD29) and angiogenic factors (CD31 and VEGF) were also down-regulated as examined by immunofluorescence. In addition, the CM obtained from HBL-100 enhanced the migration and inhibited the adipogenic differentiation of ASCs. These results demonstrate that ASCs have the ability to transform into epithelial-like cells when cultured with mammary epithelial cells. Given these observations, we infer that ASCs have a positive effect on lipotransfer, not only due to their ability to secrete growth factors, but also due to their direct participation in the formation of new breast tissue. [ABSTRACT FROM AUTHOR]

Fat transplantation is increasingly used in breast augmentation; and recently, the issue of safety concerns from a cellular and molecular point of view has been raised. In this study, attentions were paid to the interaction between adipose-derived stem cells (ADSC) and mammary epithelial cells: human breast cancer cell line - 100 (HBL - 100) cells were used to simulate the normal microenvironment in breast tissue, ADSCs were harvest from human and co-cultured with HBL-100 cells. It was found that ADSCs formed tube-like structures in the co-culture with HBL-100 cells in contrast to the normal morphology of ADSCs in the control group. In addition, the immunofluorescence imaging showed that cytokeratin 18 and 19 (CK18 and 19) were significantly expressed in ADSCs after the co-culture with HBL-100 cells. The ultrastructure of those ADSCs also showed epithelial changes. In conclusion, ADSCs are not biological stable when co-cultured with HBL-100 cells. They differentiate into epithelial-like cells with the expression of epithelial surface marks (CK 18, 19) and form tube-like structures. This may offer an important evidence for the further study of clinical application of transplanting ADSCs rich adipose tissue into the breast in the future. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a leading cause of mortality and permanent disability, with enormous financial repercussions on health systems worldwide. Ischemic brain injury results from a complex sequence of pathophysiological events that evolve over time. In order to examine the molecular mechanisms underlying middle cerebral artery occlusion (MCAO)-induced ischemic stroke, the GSE35338 affymetrix microarray data was obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) between samples from patients with MCAO-induced ischemic stroke and sham controls at various time points were identified. Furthermore, protein-protein interaction (PPI) networks were constructed by mapping the DEGs into PPI data to identify the pathways that these DEGS are involved in. The results revealed that the expression of 438 DEGs, which are mainly involved in cell death, oxidant reduction, cell cycle and cell-cell signaling, were altered in MCAO samples. The nodes of CXC motif chemokine 10 (CXCL10) and interleukin-6 (IL-6) were large, with degrees of >20. In conclusion, the results suggest that CXCL10 and IL-6 have important roles in the occurrence and progression of MCAO-induced ischemic stroke. [ABSTRACT FROM AUTHOR]

Despite recent advances in understanding the biological behavior of osteosarcoma (OS), OS is still the most common primary bone sarcoma that endangers the health of children and adolescents. High-temperature requirement A (HTRA) protease family plays an important regulatory role in numerous malignancies and acts as a prognostic biomarker. However, the function and underlying mechanisms of the HTRA family in OS development remain unknown. Through analyzing the GSE126209 dataset obtained from different Gene Expression Omnibus (GEO) databases, we found that HTRA3 as a member of the HTRA family was downregulated in OS tissues compared with that in normal tissues. Functional experiments indicated that HTRA3 overexpression suppressed malignant behaviors of OS cells in vitro and tumor growth in vivo. Mechanistically, we found that HTRA3 co-localized with the X-linked inhibitor of apoptosis protein (XIAP) and decreased XIAP stability. Further investigation showed that XIAP knockdown inhibited the degradation of phosphatase and tensin homolog (PTEN) and that HTRA3 caused the blockage of PTEN/phosphoinositide 3-kinase (PI3K)/AKT pathway, characterized as the reverse of cell function caused by HTRA3 overexpression after PTEN inhibitor BpV (HOpic) treatment. Detailed investigations showed that forkhead box protein 1 (FOXP1), an oncogene in OS progression, downregulated HTRA3 expression and inhibited the transcriptional activity of HTRA3 , suggesting that HTRA3 was regulated negatively by FOXP1. In conclusion, our study demonstrates that HTRA3 is a repressor involved in OS development via the PTEN/PI3K/AKT pathway under the modulation of transcription factor FOXP1, and it may provide a therapeutic direction for OS patients. [Display omitted] • High-temperature requirement A3 (HTRA3), was screened as the candidate oncogene by the bioinformatic analysis. • HTRA3 was downregulated in osteosarcoma (OS) tissues and cells. • HTRA3 overexpression induced cell apoptosis and inhibited cell migration and invasion. • HTRA3 co-localized with the X-linked inhibitor of apoptosis protein (XIAP) and decreased XIAP stability. • XIAP knockdown inhibited the degradation of phosphatase and tensin homolog (PTEN). • HTRA3 suppressed the PTEN/PI3K/AKT pathway, a crucial signaling pathway contributed to the OS tumorigenesis. • Transcription factor FOXP1 was confirmed to impede the activity of HTRA3 promoter. [ABSTRACT FROM AUTHOR]

With the exaggerated growth of solid tumor, the depletion of O 2 in interior cells far exceeds their blood supply, leading to low levels of O 2 in tumor microenvironment (Hypoxia). Low concentration of O 2 often cause many problems in tumor cells, including poor prognosis, increased metastasis and pro-survival changes in gene expression. Thus, developing new imaging strategy for living cells under hypoxic conditions is strongly desirable. In this review, we discuss recent progress in hypoxia-responsive fluorescent nanoprobes for imaging and cancer therapy. First, we describe two basic elements of fluorescent nanoprobes, including recognition moiety and nanomaterial-based carrier. Then, recent progress in fluorescent nanoprobes for imaging under hypoxic conditions is summarized. Finally, we outline development of hypoxia-responsive fluorescent nanoprobes for simultaneous imaging and cancer treatment. We aim to provide a comprehensive summary of application for distinguishing tumor hypoxic status, diagnosing disease and developing hypoxia-responsive anticancer nanodrugs. Image 1 • The importance of hypoxia-responsive imaging and therapy has been highlighted. • Two basic elements for fabrication of hypoxia-responsive nanoprobe are recognition moiety and nanomaterial-based carrier. • Mechanisms of moieties response to hypoxia are explained, and characteristics of fluorescent nanoprobes are presented. • We focus on recent progress in hypoxia-responsive fluorescent nanoprobes for imaging and cancer therapy. [ABSTRACT FROM AUTHOR]