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Tooth enamel, a highly mineralized tissue covering the outermost area of teeth, is always damaged by dental caries or trauma. Tooth enamel rarely repairs or renews itself, due to the loss of ameloblasts and dental epithelial stem cells (DESCs) once the tooth erupts. selleckchem Unlike human teeth, mouse incisors grow continuously due to the presence of DESCs that generate enamel-producing ameloblasts and other supporting dental epithelial lineages. The ready accessibility of mouse DESCs and wide availability of related transgenic mouse lines make mouse incisors an excellent model to examine the identity and heterogeneity of dental epithelial stem/progenitor cells; explore the regulatory mechanisms underlying enamel formation; and help answer the open question regarding the therapeutic development of enamel engineering. In the present review, we update the current understanding about the identification of DESCs in mouse incisors and summarize the regulatory mechanisms of enamel formation driven by DESCs. The roles of DESCs during homeostasis and repair are also discussed, which should improve our knowledge regarding enamel tissue engineering.Quiescent state has been observed in stem cells (SCs), including in adult SCs and in cancer SCs (CSCs). Quiescent status of SCs contributes to SC self-renewal and conduces to averting SC death from harsh external stimuli. In this review, we provide an overview of intrinsic mechanisms and extrinsic factors that regulate adult SC quiescence. The intrinsic mechanisms discussed here include the cell cycle, mitogenic signaling, Notch signaling, epigenetic modification, and metabolism and transcriptional regulation, while the extrinsic factors summarized here include microenvironment cells, extracellular factors, and immune response and inflammation in microenvironment. Quiescent state of CSCs has been known to contribute immensely to therapeutic resistance in multiple cancers. The characteristics and the regulation mechanisms of quiescent CSCs are discussed in detail. Importantly, we also outline the recent advances and controversies in therapeutic strategies targeting CSC quiescence.Breast cancer, like many other cancers, is believed to be driven by a population of cells that display stem cell properties. Recent studies suggest that cancer stem cells (CSCs) are essential for tumor progression, and tumor relapse is thought to be caused by the presence of these cells. CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies. Additionally, the metabolic properties of cancer cells differ markedly from those of normal cells. The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells. Metabolic targeting of breast CSCs (BCSCs) may be a very effective strategy for anti-cancer treatment of breast cancer cells. Thus, in this review, we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases, injury repair, degenerative diseases, and tumors. Exosomes are small vesicles rich in a variety of nucleic acids [including messenger RNA, Long non-coding RNA, microRNA (miRNA), and circular RNA], proteins, and lipids. Exosomes can be secreted by most cells in the human body and are known to play a key role in the communication of information and material transport between cells. Like exosomes, miRNAs were neglected before their role in various activities of organisms was discovered. Several studies have confirmed that miRNAs play a vital role within exosomes. This review focuses on the specific role of miRNAs in MSC-derived exosomes (MSC-exosomes) and the methods commonly used by researchers to study miRNAs in exosomes. Taken together, miRNAs from MSC-exosomes display immense potential and practical value, both in basic medicine and future clinical applications, in treating several diseases.There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus. Diabetic tendinopathy is an important cause of chronic pain, restricted activity, and even tendon rupture in individuals. Tenocytes and tendon stem/progenitor cells (TSPCs) are the dominant cellular components associated with tendon homeostasis, maintenance, remodeling, and repair. link2 Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy. In this review, the biomechanical properties and histopathological changes in diabetic tendons are described. Then, the cellular and molecular alterations in both tenocytes and TSPCs are summarized, and the underlying mechanisms involved are also analyzed. A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells, resistance to chemotherapy and radiotherapy, and tumor regression capacity. In recent years, it has been shown that the presence of breast cancer stem cells is closely associated with the migration and metastatic ability of cancer cells, as well as with their resistance to chemotherapy and radiotherapy. The tumor microenvironment is one of the main molecular factors involved in cancer and metastatic processes development, in this sense it is interesting to study the role of platelets, one of the main communicator cells in the human body which are activated by the signals they receive from the microenvironment and can generate more than one response. Platelets can ingest and release RNA, proteins, cytokines and growth factors. After the platelets interact with the tumor microenvironment, they are called "tumor-educated platelets." Tumor-educated platelets transport material from the tumor microenvironment to sites adjacent to the tumor, thus helping to create microenvironments conducive for the development of primary and metastatic tumors. It has been observed that the clone capable of carrying out the metastatic process is a cancer cell with stem cell characteristics. Cancer stem cells go through a series of processes, including epithelial-mesenchymal transition, intravasation into blood vessels, movement through blood vessels, extravasation at the site of the establishment of a metastatic focus, and site colonization. Tumor-educated platelets support all these processes.Breast tumor segmentation provides accurate tumor boundary, and serves as a key step toward further cancer quantification. Although deep learning-based approaches have been proposed and achieved promising results, existing approaches have difficulty in detecting small breast tumors. The capacity to detecting small tumors is particularly important in finding early stage cancers using computer-aided diagnosis (CAD) systems. In this paper, we propose a novel deep learning architecture called Small Tumor-Aware Network (STAN), to improve the performance of segmenting tumors with different size. The new architecture integrates both rich context information and high-resolution image features. We validate the proposed approach using seven quantitative metrics on two public breast ultrasound datasets. The proposed approach outperformed the state-of-the-art approaches in segmenting small breast tumors.Separating overlapped nuclei is a major challenge in histopathology image analysis. Recently published approaches have achieved promising overall performance on public datasets; however, their performance in segmenting overlapped nuclei are limited. To address the issue, we propose the bending loss regularized network for nuclei segmentation. The proposed bending loss defines high penalties to contour points with large curvatures, and applies small penalties to contour points with small curvature. Minimizing the bending loss can avoid generating contours that encompass multiple nuclei. The proposed approach is validated on the MoNuSeg dataset using five quantitative metrics. It outperforms six state-of-the-art approaches on the following metrics Aggregate Jaccard Index, Dice, Recognition Quality, and Panoptic Quality.[This corrects the article on p. 4277 in vol. 12, PMID 32913504.].Sclerosis variant in carotid body tumor (CBT) is characterized by extensive stromal sclerosis, which results in an uncommon pattern of growth that closely resembles that of an invasive malignant neoplasm. However, the clinical significance and the mechanism remains unclear. In this study, we provide evidence that SS-31 exerts protective effects against SDHB suppression-mitochondrial dysfunction-EndMT axis-modulated CBT sclerosis and progression. In human CBT specimens, sclerosis extent was consistently related to decreased recurrence-, death-, systematic metastasis-, and major adverse event-free survival, decreased SDHB expression, and aggravated EndMT. link3 In human umbilical vein endothelial cells (HUVECs), SDHB KD aggravated hypoxia-induced EndMT, mitochondrial dysfunction and metabolic switch, while SS-31 treatment could significantly attenuate these changes caused by SDHB KD and hypoxia. In patient-derived xenograft (PDX) mice models of CBT, we also observed increased tumor growth speed and extent of EndMT, mitochondrial dysfunction, and metabolic switch in sclerosing carotid body tumor (SCBT) group than in conventional carotid body tumor (CCBT) group. And treating with SS-31 could significantly retard SCBT progression by rescuing the mitochondrial dysfunction-induced EndMT. Altogether, these results show that SDHB suppression-mitochondrial dysfunction-EndMT axis is a critical part of the CBT sclerosis and progression, while mitochondria-targeted drug SS-31 exerts an inhibitive effect on the above-mentioned axis, which opens new strategies to prevent and treat malignancies of CBT.With continuous disclosure of the significance of long non-coding RNAs (lncRNAs) in gene expression, the role of lncRNAs in malignant tumors has attracted extensive attention of scholars. Many types of studies found that lncRNA MNX1-AS1 is an over-expressed lncRNA in various malignant tumors. Results also indicate that MNX1-AS1 participates in the biological processes of cancers. Recent studies found that lncRNA MNX1-AS1 has high sensitivities and specificities in tumor tissues and plasma and may be a potential diagnostic biomarker and prognostic predictor. The biological functions of lncRNA MNX1-AS1 and its mechanisms of function in tumors were comprehensively reviewed in this article to lay a molecular foundation for future clinical applications of MNX1-AS1.

The association between LINC01305, a newly discovered long non-coding RNA (lncRNA), and cervical cancer (CC) has been poorly analyzed. In the present study, we revealed high expression of LINC01305 in CC by the cancer genome atlas (TCGA) and Gene Expression Omnibus (GEO), and dissected the related mechanisms.

LINC01305, microRNA (miR) -129-5p and SRY-related high-mobility group box 4 (Sox4) mRNA levels were quantitated by quantitative reverse transcription-PCRy qRT-PCR). CC tissues and cell lines and corresponding controls were enrolled for the quantification of LINC01305 expression in CC. Effects of LINC01305 and miR-129-5p on cell proliferation, metastasis, and apoptosis were evaluated by MTT, colony formation, wound healing, Transwell and flow cytometry assays. Sox4 protein levels were tested by Western blot (WB). Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and dual-luciferase reporter (DLR) assay were performed to determine molecular mechanisms of LINC01305 in CC. Xenograft models of CC were constructed to evaluate the role of LINC01305 in vivo.