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The expression levels of miR-365 vary in different malignancies. Herein, we found that miR-365 was overexpressed in both cells and clinical specimens of cutaneous squamous cell carcinoma (SCC). We demonstrated that the HaCaTpre-miR-365-2 cell line, which overexpressed miR-365, could induce subcutaneous tumors in vivo. Antagomir-365, an anti-miR-365 oligonucleotide, inhibited cutaneous tumor formation in vivo, along with G1 phase arrest and apoptosis of cancer cells. These findings suggest that miR-365 may act as an onco-miR in cutaneous SCC both in vitro and in vivo. The present study provides valuable insight into the role of miR-365 in cutaneous SCC formation, which can help develop new drug and miR-365 target-based therapies for cutaneous SCC.

The aim of the present study was to obtain the prevalence of malocclusions in preschool children in Shanghai, China. A cross-sectional survey was conducted among 2335 children aged 3–5 years from kindergartens. Several occlusal parameters were clinically assessed, including second deciduous molar terminal plane, canine relationship, degree of overjet and overbite, anterior and posterior crossbite, and the presence or absence of physiologic spaces and crowding. All parents of subjects were asked to fill in the oral health knowledge questionnaires. The prevalence of malocclusion in primary dentition in Shanghai was 83.9%, and no significant differences were found in genders. Data showed that the prevalence of deep overbite (63.7%) was the highest in children with malocclusion, followed by deep overjet (33.9%), midline deviation (26.6%), anterior crossbite (8.0%) and anterior crowding (6.5%). The results revealed a high prevalence of malocclusion in primary dentition in children aged 3–5 years old of Shanghai, especially in vertical anomalies. The need for preventive orthodontic therapy is extremely desired and oral health education about malocclusion should be strengthened.

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CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene. Our study was carried out to examine the role of CD99 in tumor progression of classical Hodgkin lymphoma (cHL). Here, we showed that lowly expressed CD99 protein in cHL cell lines and primary cHL cases correlates with the deficient expression of the positive regulatory domain 1 (PRDM1/ BLIMP1). In addition, cHL cell lines showed high levels of miR-9 expression. We determined that the upregulation of CD99 induced expression of transcription factor PRDM1, a master regulator of plasma-cell differentiation, which is also a target for miR-9-mediated downregulation. Indeed, inhibition of miR-9 also triggered upregulation of PRDM1 expression. Furthermore, overexpression of CD99 resulted in changed growth features and reorganization of actin cytoskeleton. As upregulation of CD99 led to a decrease in cHL diagnosis marker CD30 and CD15 and an increase in plasma-cell differentiation marker CD38 and the restoration of B-cell makers PAX5, CD79a and CD19, we suggest that downregulated CD99 leads to the prevention of plasma-cell differentiation in Hodgkin/Reed-Sternberg (H/RS) cells. Furthermore, these data indicate that CD99 may control miR-9 expression, which directly targets PRDM1. Altogether, these results reveal a CD99-miR-9-PRDM1 molecule axis in lymphomagenesis of cHL and suggest that upregulation of CD99 in H/RS cells induces terminal B-cell differentiation, which may provide a novel therapeutic strategies for cHL.The classical Hodgkin lymphoma (cHL) is a malignant lymphoma characterized by the presence of rare Hodgkin and Reed-Sternberg (H/RS) cells residing in a complex admixture of inflammatory cells. Although the nature of H/RS cells is still difficult to interpret, H/RS cells have evidence of abortive plasma-cell differentiation. 1 Recent published data showed that blockage of terminal B-cell differentiation may play a role in the pathogenetic mechanisms of B-cell lymphoma. [2][3][4] The positive regulatory domain 1 (PRDM1), also known as Blimp-1, is a transcriptional repressor that is a master regulator of terminal differentiation of B-cells into plasma cells. 5,6 It also plays a critical role in T FH and CD8 þ T-cell differentiation, 7,8 myeloid differentiation, 9 dendritic cell homeostatic development 10 and NK cell maturation. 11 PRDM1 is found in all plasma cells and in a small proportion of germinal center (GC) cells. 1 In the course of plasmacell differentiation, PRDM1 inhibits GC-B cell repressor BCL6, which can also repress expression of PRDM1. 12 MUM1/IRF4, expressed at high levels in plasma cells, coexpressed with PRDM1, is also critical for plasma-cell differentiation. 13 The consistent expression of MUM1 in H/RS cells demonstrates evidence of initial plasma-cell commitment and proposes a potential plasma-cell differentiation. 1 CD99, encoded by the MIC2 gene, is a human 32-kDa transmembrane glycoprotein, which is highly expressed in Ewing's sarcoma, anaplastic large-cell lymphoma, thymocytes and peripheral T cells. 14-17 CD9...

Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma that includes two forms of BL differing in Epstein-Barr virus (EBV) infection status, EBV-positive and EBV-negative. Although many efforts, such as high-intensity, short-duration combination chemotherapy, have been devoted to improving therapy for this rapidly proliferating neoplasm, there are still significant treatment-associated toxicities. Therefore, there remains a need for novel effective therapeutic strategies. MicroRNAs play a role in "fine tuning" the physiological and pathological differentiation process, by which cells can rapidly regulate dynamic events such as cell-lineage decisions and morphogenesis. This unique miRNA feature shifts the traditional one drug target paradigm to a novel one drug multiple targets paradigm. Here, we found that BL cell lines showed an extremely low expression of microRNA-150 (miR-150), and then restored miR-150 expression at physiologic levels in BL cell lines Daudi, Raji, BJAB, and Ramos. The results showed that re-expression of miR-150 reduced proliferation of Daudi and Raji cells. B urkitt lymphoma is a highly aggressive B-cell malignancy, identified and described for the first time by Dennis Burkitt in 1958.(1) According to the EBV infection status, BLs are divided into two subgroups, EBV-positive and EBV-negative.(2) Burkitt lymphomas have a tendency to morphologically resemble germinal center (GC) cells, (3) and to immunophenotypically express characteristic GC cell markers such as CD10 and BCL6, and coexpress B-cell markers CD19 and CD20, (4) which suggests follicle center B-cell origin for this lymphoma. In recent years, efforts have focused on improving therapy for this, the fastest growing human tumor, while minimizing treatment-associated toxicity. Outcome with intensive chemotherapy has improved and is now excellent in children, but the prognosis is poor in elderly adults. In addition, there are significant associated toxicities, such as frequent myelosuppression, mucositis, neuropathy, and complication of tumor lysis syndrome.(5,6) Therefore, it is imperative and important to pursuit more effective therapies.MicroRNAs, a novel class of small non-coding RNAs of approximately 19-26 nt, exert multiple cellular functions and play critical roles in cellular proliferation, apoptosis, cellular differentiation, and tumorigenesis.(7-9) MicroRNA expression profiling studies have found that in hematopoiesis, certain miRNAs are expressed in a stage-specific fashion in the lymphoid hematopoietic system.(10-14) Therefore, deregulations of their expression may result in the development of hematopoietic malignancies. (15) MicroRNA-150 has attracted our great attention in hematopoiesis among a large number of miRNAs in recent years, which has been studied in B, T, and NK ⁄ T cells. (16)(17)(18)(19)(20) There is strong evidence that miR-150 is preferentially expressed in mature lymphocytes, but not their progenitors. Ectopic miR-150 expression of murine hematopoietic stem cells impairs the transition of pro-B to pre...

Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer’s disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3×Tg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functions, and the hippocampal tissues were examined by protein analysis and quantitative proteomics. Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3×Tg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Aβ1–40 and Aβ1–42) and senile plaques were reduced in the hippocampus. Golgi staining of the hippocampus showed that donepezil prevented dendritic spine loss in hippocampal neurons of 3×Tg-AD mice. Proteomic studies of the hippocampal tissues identified 3131 proteins with altered expression related to AD pathology, of which 262 could be significantly reversed with donepezil treatment. Bioinformatics with functional analysis and protein–protein interaction (PPI) network mapping showed that donepezil significantly elevated the protein levels of PINK 1, NFASC, MYLK2, and NRAS in the hippocampus, and modulated the biological pathways of axon guidance, mitophagy, mTOR, and MAPK signaling. The substantial upregulation of PINK 1 with donepezil was further verified by Western blotting. Donepezil exhibited neuroprotective effects via multiple mechanisms. In particular, PINK 1 is related to mitophagy and cellular protection from mitochondrial dysfunction, which might play important roles in AD pathogenesis and represent a potential therapeutic target.

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