The Stability of Physician-Compounded Foam is Influenced by the Angle of Connector.

BACKGROUND: Foam sclerotherapy is an effective treatment for varicose veins and venous malformations, with its efficacy influenced by foam stability. The methods for preparing physician-compounded foam (PCF) are the double syringe system (DSS) and Tessari method. Few studies have been performed to compare the PCF stability produced by the 2 methods and their mechanisms. We aim to compare the stability of PCF produced by 2 two methods in the same connector and explore the reasons for the difference. METHODS: Foam was generated by the 2 methods under different circumstances. In the Tessari method, 2 syringes were connected at right angles (90°) by a 3-way tap. In the DSS method, 2 syringes were connected by the same 3-way tap in a straight line (180°). The stability and uniformity of foam produced by the 2 methods were compared using foam half-time and optical microscopy, respectively. Assuming that the difference in foam stability between the 2 methods was related to the angles of a connector, we compared the foam stability when 2 syringes were connected with a plastic connector bent to different angles. RESULTS: The DSS method could produce more uniform foam with longer foam half-time than the Tessari method, which was related to the angle of the connector. CONCLUSIONS: The stability of PCF is influenced by the angle of the connector.

Itraconazole inhibits proliferation, induces apoptosis, and reduces angiogenesis of hemangioma endothelial cells by downregulating the hedgehog signaling pathway.

Infantile hemangioma (IH) is among the most prevalent benign vascular tumours in infants. The pathogenesis of IH mainly involves abnormal proliferation of vascular endothelial cells and the formation of new vessels. Itraconazole was shown to be effective in treating IH; however, the mechanism underlying its action is still unclear. The purpose of this study was to examine the effects of itraconazole on the proliferation, apoptosis, and angiogenesis of hemangioma endothelial cells (HemECs); human umbilical vein endothelial cells served as the control group. The expression of genes involved in the hedgehog (HH) signaling pathway (SHH, PTCH1, SMO, and GLI1) was determined using real-time quantitative polymerase chain reaction. Western blotting was used to determine the expression of related proteins. In this study, itraconazole significantly dose- and time-dependently inhibited the viability of HemECs. Itraconazole suppressed the expression of PCNA, Ki67, and vascular endothelial growth factor (VEGF), demonstrating that this treatment inhibited cell proliferation and angiogenesis. Moreover, itraconazole induced apoptosis of HemECs by activating the expression of BAX and inhibiting the expression of BCL2. Itraconazole inhibited SHH, PTCH1, SMO, and GLI1 expression. Activation of the HH pathway by recombinant human sonic hedgehog (rhSHH) protein attenuated the effect of itraconazole on HemECs. In conclusion, itraconazole inhibits proliferation, induces apoptosis, and reduces angiogenesis of HemECs via the downregulation of the HH signaling pathway. Therefore, itraconazole may be an alternative choice for the treatment of IH.

Microbiome landscape of lesions and adjacent normal mucosal areas in oral lichen planus patient.

The pathogenesis of oral lichen planus (OLP) remains unclear, and microbial dysbiosis has been proposed to play a role in the pathogenesis of OLP. Oral mucosal swabs from 77 OLP patients and 76 healthy subjects were collected. The bacterial community among the OLP lesion, the adjacent normal mucosal, and the oral mucosal surface in healthy people were analyzed by 16S sequencing. The factor of gender and age that may affect the flora distribution of OLP patients were explored. Results indicate no significant difference in microbiota between OLP and the adjacent group. Compared with the healthy group, Neisseria, Haemophilus, Fusobacterium, Porphyromonas, Rothia, Actinomyces, and Capnocytophaga significantly increased in the OLP group. Actinomyces increased in male OLP patients, and the other six bacteria increased in female OLP patients. In female OLP patients, Lautropia and Dialister were positively correlated with age. While in male OLP patients, Moraxella, Porphyromonas, and Fusobacterium were positively correlated with age. Functional enrichment analysis suggested that abnormal energy metabolism related to ATP synthases, abnormal transport and metabolism of glycans, amino acids, and vitamins, and disorders of the local immune microenvironment might exist in OLP lesion.

Constitutively Photomorphogenic 1 Reduces the Sensitivity of Chronic Lymphocytic Leukemia Cells to Fludarabine Through Promotion of Ubiquitin-Mediated P53 Degradation.

BACKGROUND/AIMS: Chronic Lymphocytic leukemia (CLL) is characterized by accumulation of cells in the G0/G1 phase of the cell cycle and resistance to apoptosis due to gene mutation or abnormal gene expression. In our previous study, constitutively photomorphogenic 1 (COP1) was shown to be upregulated in Binet C-phase CLL patients. Based on the negative regulation of COP1 in the repair of DNA damage, we further studied the function of COP1 in CLL cell apoptosis induced by fludarabine in vitro and in vivo. METHODS: We analyzed the sensitivity of primary CLL cells to the fludarabine by CCK-8, and detected the expression of p53 in cells after drug treatment by western blot. Next, we constructed COP1 overexrpessing CLL cell line HG3, and analyzed the effect of COP1 overexpression on the HG3 cell's apoptosis, and HG3 transplant mice survival with drug treatment. RESULTS: Here, we found that primary CLL cells with high expression of COP1 showed low sensitivity to the drug and presented delayed enrichment of p53 protein than cells with low COP1 expressed. COP1 overexpression reduced HG3 cell sensitivity to the fludarabine treatment and inhibited cell apoptosis, and also retarded itself via autoubiquitination. The further study showed that COP1 promoted ubiquitin-dependent p53 degradation, which further disrupts the formation of the p53-Brn-3a complex and activation of Bcl-2 transcription. Moreover, mice engrafted with cells overexpressing COP1 showed a shortened survival, increased tumor cells burden in spleen and bone marrow (BM), and reduced tumor cell apoptosis even when fludarabine combined cyclophosphamide (F+C) therapy was administered. CONCLUSION: This study demonstrates that COP1 contributes to drug resistance of CLL cells to the fludarabine treatment in vitro and in vivo.

Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells in response to traditional therapeutic medicine. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a natural compound from Plumbago zeylinica, has been shown to exhibit pro-apoptotic activities in tumor cells. In the present study, we report that plumbagin effectively inhibited CLL cell viability with a lower dose compared to fludarabine, and inhibited cell proliferation in a dose-dependent manner. In addition, plumbagin promoted accumulation of MEC-1 cells in the S phase, and blocked cell cycle transition of HG3 cells from G0/G1 to S phase. Molecularly, plumbagin markedly induced CLL cell apoptosis through reduction of Bcl-2, but through an increase in the Bax protein level. These results suggest that plumbagin may be considered as a potential anticancer agent for CLL therapy.

Expression and regulation of COP1 in chronic lymphocytic leukemia cells for promotion of cell proliferation and tumorigenicity.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis. The aberration of proliferation-related gene in CLL cells induces cell arrest at G0/G1 phase, or a small section shows rapid cell growth, which further complicates the pathogenesis of CLL. The constitutively photomorphogenic 1 (COP1), as an E3 ubiquitin ligase, is involved in many biological processes in mammalian cells, but its role in chronic lymphocytic leukemia (CLL) progression remains unclear. In the present study, we analyzed the expression of COP1 in peripheral blood mononuclear cells (PBMCs) from 23 CLL patients and 3 healthy donors. The observed upregulated expression of COP1 in CLL patients was positively correlated with CLL clinical stage and ZAP-70 expression, but not del(13q14) and del(17q-). Overexpression of COP1 significantly promoted cell colony formation and proliferation, especially contributing to the accumulation of cells in S-phase by inhibition of FoxO1 and p21. Moreover, overexpression of COP1 accelerated tumorigenicity of HG3 cells and promoted xenograft growth. Therefore, the present study revealed that COP1 plays an important role in CLL cell proliferation and tumorigenicity, and may be a useful indicator of the chronic lymphocytic leukemia processes.