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Multifunctional nanoplatforms with integrated diagnostic and therapeutic functions have attracted tremendous attention. Especially, the second near-infrared (NIR-II) light response-based nanoplatforms hold great potential in cancer theranostic applications, which is because the NIR-II window provides larger tissue penetration depth and higher maximum permissible exposure (MPE) than that of the well-studied first near-infrared (NIR-I) window. Herein, we for the first time present a two-dimensional (2D)-nanoplatform based on Cu2MnS2 nanoplates (NPs) for magnetic resonance imaging (MRI)/multispectral optoacoustic tomography (MSOT) dual-modal imaging-guided photothermal therapy (PTT) of cancer in the NIR-II window. Methods: Cu2MnS2 NPs were synthesized through a facile and environmentally friendly process. A series of experiments, including the characterization of Cu2MnS2 NPs, the long-term toxicity of Cu2MnS2 NPs in BALB/c nude mice, the applications of Cu2MnS2 NPs for in vitro and in vivo MRI/MSOT dual-modal imaging and NIR-II PTT of cancer were carried out. Results: The as-synthesized Cu2MnS2 NPs exhibit low cytotoxicity, excellent biocompatibility as well as high photothermal conversion efficiency (~49.38%) and outstanding photostability. Together with their good T1-shortening effect and strong absorbance in the NIR-I and NIR-II region, the Cu2MnS2 NPs display high-contrast imaging performance both in MRI and MSOT (900 nm laser source). Moreover, the subsequent in vitro and in vivo results demonstrate that the Cu2MnS2 NPs possess excellent PTT efficacy under 1064 nm laser irradiation with a low power density (0.6 W cm-2). In addition, the detailed long-term toxicity studies further confirming the safety of Cu2MnS2 NPs in vivo. Conclusion: We have developed a new 2D Cu2MnS2 NPs as multifunctional theranostic agents for MRI/MSOT dual-modal imaging-guided PTT of cancer in the NIR-II window. Such biocompatible Cu2MnS2 NPs might provide a new perspective for exploring new 2D-based nanoplatforms with improved properties for clinical applications in the future.

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Transcription factor B-cell lymphoma/leukemia 11A (BCL11A) gene encodes a zinc-finger protein that is predominantly expressed in brain and hematopoietic tissue. BCL11A functions mainly as a transcriptional repressor that is crucial in brain, hematopoietic system development, as well as fetal-to-adult hemoglobin switching. The expression of this gene is regulated by microRNAs, transcription factors and genetic variations. A number of studies have recently shown that BCL11A is involved in β-hemoglobinopathies, hematological malignancies, malignant solid tumors, 2p15-p16.1 microdeletion syndrome, and Type II diabetes. It has been suggested that BCL11A may be a potential prognostic biomarker and therapeutic target for some diseases. In this review, we summarize the current research state of BCL11A, including its biochemistry, expression, regulation, function, and its possible clinical application in human diseases.

Background Pulpitis is a common inflammatory disease that affects dental pulp. It is important to understand the molecular signals of inflammation and repair associated with this process. Increasing evidence has revealed that long noncoding RNAs (lncRNAs), via competitively sponging microRNAs (miRNAs), can act as competing endogenous RNAs (ceRNAs) to regulate inflammation and reparative responses. The aim of this study was to elucidate the potential roles of lncRNA, miRNA and messenger RNA (mRNA) ceRNA networks in pulpitis tissues compared to normal control tissues. Methods The oligo and limma packages were used to identify differentially expressed lncRNAs and mRNAs (DElncRNAs and DEmRNAs, respectively) based on expression profiles in two datasets, GSE92681 and GSE77459, from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) networks and modules were established to screen hub genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) plugin for Cytoscape, respectively. Furthermore, an lncRNA-miRNA-mRNA-hub genes regulatory network was constructed to investigate mechanisms related to the progression and prognosis of pulpitis. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify critical lncRNAs that may significantly affect the pathogenesis in inflamed and normal human dental pulp. Results A total of 644 upregulated and 264 downregulated differentially expressed genes (DEGs) in pulpitis samples were identified from the GSE77459 dataset, while 8 up- and 19 downregulated probes associated with lncRNA were identified from the GSE92681 dataset. Protein–protein interaction (PPI) based on STRING analysis revealed a network of DEGs containing 4,929 edges and 623 nodes. Upon combined analysis of the constructed PPI network and the MCODE results, 10 hub genes, including IL6, IL8, PTPRC, IL1B, TLR2, ITGAM, CCL2, PIK3CG, ICAM1, and PIK3CD, were detected in the network. Next, a ceRNA regulatory relationship consisting of one lncRNA (PVT1), one miRNA (hsa-miR-455-5p) and two mRNAs (SOCS3 and PLXNC1) was established. Then, we constructed the network in which the regulatory relationship between ceRNA and hub genes was summarized. Finally, our qRT-PCR results confirmed significantly higher levels of PVT1 transcript in inflamed pulp than in normal pulp tissues (p = 0.03). Conclusion Our study identified a novel lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of pulpitis.

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This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Despite advances in treatment modalities, 5-year survival among glioma patients remains poor. Glioma cancer stem cells (CSCs) exhibit high tumorigenic activity and are associated with resistance to treatment and tumor recurrence. Because overexpression of toll-like receptor 4 (TLR4) correlated with cancer development, we investigated LPS-induced TLR4 signaling in glioma CD133-positive (CD133+) CSCs. The proliferation of CD133+ CSCs isolated from CSCs derived from the U251 and SF295 glioma cell lines and from human glioma samples was upregulated on a time- and concentration-dependent basis by LPS stimulation, with increases in CD133, NANOG, and NESTIN mRNA and protein levels. Also elevated was cytokine expression, which was coupled to phosphorylation of mitogen-activated protein kinase, and activation of cyclins and cyclin-dependent kinase complexes. TLR4 knockdown reduced LPS-induced CD133+ CSC proliferation, whereas Adriamycin-induced CD133+ CSC apoptosis was moderately inhibited by treatment with LPS, implying a protective effect of LPS. The capacity of glioma CD133+ CSC-reactive cytotoxic T lymphocyte to selectively kill CD133+ CSCs was reduced by LPS, and this effect was not apparent after TLR4 knockdown in CD133+ CSCs. These data suggest TLR4 signaling is a factor in CD133+ CSC immune evasion, and thus disruption of TLR4 signaling is a potential therapeutic strategy in glioma.