RNA-seq reveals tight junction-relevant erythropoietic fate induced by OCT4 in human hair follicle mesenchymal stem cells.

BACKGROUND: Human hair follicle mesenchymal stem cells (hHFMSCs) isolated from hair follicles possess multilineage differentiation potential. OCT4 is a gene critically associated with pluripotency properties. The cell morphology and adhesion of hHFMSCs significantly changed after transduction of OCT4 and two subpopulations emerged, including adherent cells and floating cell. Floating cells cultured in hematopoietic induction medium and stimulated with erythropoetic growth factors could transdifferentiate into mature erythrocytes, whereas adherent cells formed negligible hematopoietic colonies. The aim of this study was to reveal the role of cell morphology and adhesion on erythropoiesis induced by OCT4 in hHFMSCs and to characterize the molecular mechanisms involved. METHODS: Floating cell was separated from adherent cell by centrifugation of the upper medium during cell culture. Cell size was observed through flow cytometry and cell adhesion was tested by disassociation and adhesion assays. RNA sequencing was performed to detect genome-wide transcriptomes and identify differentially expressed genes. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by differentially expressed genes. The expression of tight junction core members was verified by qPCR and Western blot. A regulatory network was constructed to figure out the relationship between cell adhesin, cytoskeleton, pluripotency, and hematopoiesis. RESULTS: The overexpression of OCT4 influenced the morphology and adhesion of hHFMSCs. Transcripts in floating cells and adherent cells are quite different. Data analysis showed that upregulated genes in floating cells were mainly related to pluripotency, germ layer development (including hematopoiesis lineage development), and downregulated genes were mainly related to cell adhesion, cell junctions, and the cytoskeleton. Most molecules of the tight junction (TJ) pathway were downregulated and molecular homeostasis of the TJ was disturbed, as CLDNs were disrupted, and JAMs and TJPs were upregulated. The dynamic expression of cell adhesion-related gene E-cadherin and cytoskeleton-related gene ACTN2 might cause different morphology and adhesion. Finally, a regulatory network centered to OCT4 was constructed, which elucidated that he TJ pathway critically bridges pluripotency and hematopoiesis in a TJP1-dependent way. CONCLUSIONS: Regulations of cell morphology and adhesion via the TJ pathway conducted by OCT4 might modulate hematopoiesis in hHFMSCs, thus developing potential mechanism of erythropoiesis in vitro.

Myocyte-specific enhancer factor 2D promotes tumorigenesis and progression in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) ranks as one of the most common cancers worldwide and has a poor prognosis. Myocyte-specific enhancer factor 2 (MEF2D) has recently been considered as a novel factor involved in cancer development. In the present study, the function and underlying mechanism of MEF2D in TSCC were investigated. The levels of MEF2D mRNA and protein were determined in human TSCC samples by RT-qPCR and western blot, respectively. The interaction between MEF2D expression and clinicopathologic features was evaluated by IHC and analysis of clinical information. MEF2D-mediated effects on proliferation, migration, and invasion were explored in TSCC cells after transfection with MEF2D-siRNA. The results showed higher expression of MEF2D at both the mRNA and protein levels in TSCC carcinoma tissues than in paracarcinoma tissues. Furthermore, high expression of MEF2D was positively correlated with tumor differentiation and lymphatic metastasis. MEF2D knocked down TSCCA cells also had reduced proliferative, migratory, and invasive abilities compared to those of control cells. Together, these data confirmed that knockdown of MEF2D might suppress the growth and metastasis of TSCC, which further indicated that MEF2D might serve as a therapeutic target for TSCC treatment.

Experimental demonstration of fronthaul flexibility for enhanced CoMP service in 5G radio and optical access networks.

The RAN architecture towards mobile 5G and beyond is undergoing a fundamental evolution, which brings optics into the radio world. Fronthaul is a new segment that leverages on the advantages of optical communication for RAN transport. However, the current fronthaul architecture shows a fixed connection between an RRH and a BBU, which leads to inefficient resource utilization. In this paper, we focus on the fronthaul flexibility that allows "any-RRH to any-BBU" connection. In particular, we consider a CoMP service and discuss how flexible optical fronthaul helps to improve its performance. To achieve this goal, we propose an SDN-enabled orchestration for coordinating radio and optical access networks. Under this unified control manner, the agile RRH-BBU mapping can be reached through lightpath reconfiguration. To further verify the benefits of flexibility, we experiment the CoMP service in the cloud radio over flexible optical fronthaul (CRoFlex) testbed. Experimental results demonstrate the proposed SDN-enabled flexible optical fronthaul can improve the CoMP performance by optimizing the RRH-BBU mapping.

Epithelioid angiosarcoma of the kidney: A case report and literature review.

Epithelioid angiosarcoma (EAS) is a rare disease which presents a great diagnostic challenge. The present study reports a case of EAS in the kidney in a 75-year-old male who presented with gross hematuria. An abdominal computed tomography scan revealed space-occupying lesions of the right kidney and renal cell carcinoma was suspected. Histological examination of the resected specimens showed pleomorphic epithelioid cells with vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm that lined irregular vascular spaces. Immunohistochemical staining revealed that the tumor cells were positive for AE1/AE3, cytokeratin (CK) 7, vimentin, cluster of differentiation (CD) 31 and E-cadherin, but showed no staining for CD10, CD34, factor VIII, CK20, carcinoembryonic antigen or desmin. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with epithelioid angiosarcoma. Postoperative radiation therapy was administered and no recurrence was observed six months after surgery.

Ocular adnexal IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease.

IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. In the present report, we describe a case of IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease. The patient was a 55-year-old male who was being followed for right orbital tumor over 1.5 years. The lesion had recently increased in size, so a biopsy was performed. Histologically, the lesion was consistent with IgG4-related disease ; however, IgG4+ plasma cells showed immunoglobulin light-chain restriction and immunoglobulin heavy chain gene rearrangement was detected in the lesion. Therefore, the lesion was diagnosed as IgG4-producing mucosa-associated lymphoid tissue lymphoma. In conclusion, in histological diagnosis of IgG4-related disease, it is important to examine not only IgG4-immunostain but also immunoglobulin light-chain restriction.

Nodal follicular lymphoma without complete follicular dendritic cell networks is related to localized clinical stage.

Follicular lymphoma is the most common low-grade lymphoma and it frequently presents with a systemic disease, often showing advanced clinical stage (III/IV). The lymphoma cells are usually growing associated with follicular dendritic cell (FDC) networks. Abnormal FDC networks have been reported in duodenal follicular lymphoma, in which cases exhibit lower clinical stages than the nodal cases. In the present study, we analyzed the FDC network distribution pattern of 242 nodal follicular lymphomas by immunohistochemistry. Out of the 242 cases, 27 cases (11%) demonstrated an atypical pattern of FDC networks, in which the CD21 staining totally or partially disappeared in the neoplastic follicles. Furthermore, we compared the clinical data of these 27 cases and 58 typical FDC network cases of follicular lymphoma. We found that in the typical cases, 52 out of 58 patients (90%) showed advanced clinical stage (III or IV), whereas 10 of 27 (37%) atypical FDC network cases showed localized clinical stage (I or II) (P < 0.01). In conclusion, nodal follicular lymphoma with total loss or partially disrupted FDC networks therefore show a lower clinical stage.

Immunoglobulin G4-related lymphadenopathy with inflammatory pseudotumor-like features.

Immunoglobulin (Ig) G4-related disease has been recently described. This disease affects various organs, including lymph nodes. We describe the case of a 52-year-old Japanese man with IgG4-related lymphadenopathy with inflammatory pseudotumor (IPT)-like features. Five years ago, the patient noticed a painless mass in the mandible but did not consult a doctor. Recently, he noted that the mass had increased in size and consulted an oral surgeon in the hospital. Excisional biopsy was performed for diagnosis. Histopathological examination revealed that most of the enlarged lymph node was occupied by the hyalinized tissue. A few residual lymphoid follicles with hyperplastic germinal centers and infiltration of plasma cells and eosinophils were observed. Most of the plasma cells expressed IgG4, and the ratio of IgG4-positive cells to IgG-positive cells was 57.1%. These findings were consistent with IgG4-related lymphadenopathy. In conclusion, pathologists should consider IgG4-related lymphadenopathy when diagnosing a lesion with IPT-like features.

Downregulation of the B-cell receptor signaling component CD79b in plasma cell myeloma: a possible post transcriptional regulation.

The CD79 molecule, encoded by the CD79a and CD79b genes, is a signaling unit of the B-cell receptor complex, which transmits signals of B-cell activation, growth, and differentiation. They are B-cell-specific and expressed at most stages of B-cell development. Although plasma cells have been believed to lack these gene products, the regulation of CD79 expression in plasma cells is still controversial. In particular, the regulation of CD79b expression remains unclear. We sought to examine CD79b expression in normal and neoplastic plasma cells by immunohistochemical analysis. Out of the 23 clinical samples and 11 cell lines of plasma cell myeloma (PCM), none of the clinical samples and only 1 of 11 cell lines expressed CD79b immunohistologically, whereas non-neoplastic plasma cells in reactive hyperplastic lymph nodes exhibited loss of CD79b protein expression. This finding is quite different from our previous report on CD79a. Not only immunocytochemistry, but also RT-PCR and Western blot analysis of PCM cell lines gave identical results. Interestingly, we detected mRNA transcripts of CD79b in PCM cell lines, although protein translation was lacking. These findings suggest that expression of CD79b is downregulated in both plasma cells and plasma cell myeloma, and this process is possibly under post transcriptional regulation.

Multi-step aberrant CpG island hyper-methylation is associated with the progression of adult T-cell leukemia/lymphoma.

Aberrant CpG island methylation contributes to the pathogenesis of various malignancies. However, little is known about the association of epigenetic abnormalities with multistep tumorigenic events in adult T cell leukemia/lymphoma (ATLL). To determine whether epigenetic abnormalities induce the progression of ATLL, we analyzed the methylation profiles of the SHP1, p15, p16, p73, HCAD, DAPK, hMLH-1, and MGMT genes by methylation specific PCR assay in 65 cases with ATLL patients. The number of CpG island methylated genes increased with disease progression and aberrant hypermethylation in specific genes was detected even in HTLV-1 carriers and correlated with progression to ATLL. The CpG island methylator phenotype (CIMP) was observed most frequently in lymphoma type ATLL and was also closely associated with the progression and crisis of ATLL. The high number of methylated genes and increase of CIMP incidence were shown to be unfavorable prognostic factors and correlated with a shorter overall survival by Kaplan-Meyer analysis. The present findings strongly suggest that the multistep accumulation of aberrant CpG methylation in specific target genes and the presence of CIMP are deeply involved in the crisis, progression, and prognosis of ATLL, as well as indicate the value of CpG methylation and CIMP for new diagnostic and prognostic biomarkers.

[Changes of nerve growth factor and its receptors in the lung tissues in asthmatic rats and their effects on the airway inflammation].

OBJECTIVE: To determine the expression of nerve growth factor (NGF), tyrosine kinase receptor A (trkA), and pan-neurotrophin receptor (p75) in the lung tissues in asthmatic rats, and to explore their effects on the airway inflammation. METHODS: Thirty-two SD rats were randomly divided into 4 groups: the control, asthma, NGF and anti-NGF groups. The asthmatic model was established by the inhalation and injection of ovalbumin. The total cell count and differential cell count in the bronchoalveolar lavage fluid (BALF) were performed. The pathologic changes in the lung tissues of the 4 groups was detected by HE staining. The NGF mRNA expression in the lung tissues of the asthma and control groups was determined by reverse transcription-polymerase chain reaction (RT-PCR). The changes of trkA and p75 mRNA expressions in the lung tissues in the 4 groups were also investigated by RT-PCR. RESULTS: Compared with the control group, the BALF total cell, the BALF eosinophils (Eos), and the BALF lymphocytes (Lyms) significantly increased (All P <0. 001) in the asthma group; and the lung tissues of the asthma group had more infiltrating inflammatory cells. Not only the expression of NGF mRNA, but also its receptors trkA and p75 mRNA in the lung tissues were significantly higher in the asthma group than those in the control group (All P < 0.01). Positive correlation was found between the expression of NGF mRNA and the BALF total cell, the BALF Lyms in the asthma group. Compared with the asthma group, the total cell, the Eos, and the lyms in BALF in the NGF group significantly increased (All P < 0.01), and the lungs of the NGF group had apparent inflammatory changes. The expre-ssions of p75 and trkA mRNA were enhanced significantly (All P < 0.05). Compared with the asthma group, the total cell, the Eos, and the lyms in BALF in the anti-NGF group significantly decreased (All P < 0.001), and the lungs of the anti-NGF group showed alleviative inflammatory changes. The expre-ssions of p75 and trkA mRNA significantly decreased (All P < 0.01). CONCLUSION: In lungs of asthmatic rats, the elevated expression of NGF mRNA is closely related to the airway inflammation. NGF can upregulate the expressions of p75 and trkA mRNA in asthmatic rats, and then may promote their role in the airway neuronal inflammation in asthma.