Background: Tissue factor pathway inhibitor 2 (TFPI-2) has been recently identified as a tumor suppressor gene in several human cancers, whereas its role in thyroid cancer has been unclear. Methods: The TFPI-2 protein level in thyroid cancer tissues and cell lines (8305C and B-CPAP) were examined using immunohistochemistry and immunoblotting. The TFPI-2 promoter methylation was examined using methylation-specific polymerase chain reaction (MSP). Lentivirus containing TFPI-2 cDNA (Lenti-TFPI-2) was constructed to elevate TFPI-2 expression in 8305C and B-CPAP cells. The effects of Lenti-TFPI-2 on cell proliferation in vitro and in vivo were evaluated by MTT assay and mouse xenograft model. Annexin V/PI double staining assay was performed to detect the effect of Lenti-TFPI-2 on cell apoptosis. Results: TFPI-2 protein level were decreased in cancer tissues and lymph node metastasis, and TFPI-2 protein level is positively associated with survival time. The promoter of TFPI-2 is hypermethylated in cancer tissues. TFPI-2 mRNA and protein levels were abundant in normal human thyroid follicular cell line Nthy-ori 3-1 cells, whereas they were decreased in 8305C and B-CPAP cells. pcDNA-TFPI-2 elevated TFPI-2 mRNA and protein in 8305C and B-CPAP cells. TFPI-2 overexpression suppressed proliferation and induced apoptosis of 8305C and B-CPAP cells. Conclusions: TFPI-2 inactivation may play a role in thyroid cancer tumorigenesis and development. TFPI-2 overexpression suppressed cell proliferation through induction of cell apoptosis, suggesting that TFPI-2 may serve as a novel and effective target for thyroid cancer therapy.
ObjectivesHuman gut microbiome has gained great attention for its proposed roles in the development of hypertension. The fungal microbiome in the human gut (i.e. the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. However, the existing knowledge of human mycobiome has never revealed the association between gut mycobiome and hypertension. It is known that inflammation and immunity contribute to human hypertension. Here, we sought to investigate whether gut mycobiome could predict the development of hypertension and its association with immunoglobulin light chains.Methods and materialsParticipants were classified into three cohorts: prehypertension (pre-HTN), hypertension (HTN), and normal-tension (NT) based on their blood pressure. Fresh samples were collected, and the ITS transcribed spacer ribosomal RNA gene sequence was performed. An immunoturbidimetric test was used to examine the serum levels of immunological light chains.ResultsSubjects in both of the states of pre-HTN and HTN had different fungal microbiome community compared to the NT group (FDR<0.05). Slightly higher levels of fungal richness and diversity were observed in the groups of pre-HTN and HTN. The relative abundance of Malassezia increased in the HTN group compared to that in the NT group, and the relative abundance of Mortierella enriched in the NT group. For the pre-HTN group, the relative abundance of Malassezia was positively associated with serum the concentration of light chain (LC) κ (r=0.510, P=0.044); for the HTN group, the relative abundance of Mortierella was positively associated with the serum concentration of LC κ (P<0.05), the relative abundance of Malassezia was positively associated with both the serum concentrations of LC κ and LC λ (r>0.30, P<0.05).ConclusionsOur present study demonstrated that gut fungal dysbiosis occurred in the state of prehypertension, and fungal dysbiosis can predict the dysregulation of serum light chains in hypertension patients. Further study on modulating gut fungal community should be focused on balancing the immunological features in hypertension.
Cellular immunity plays important roles in clearing intracellular pathogens or tumor cells. It is of significance to develop an adjuvant able to efficaciously induce cellular immunity, but such an approved adjuvant is not currently available. Klebsiella pneumoniae (K. pneumoniae) possesses lipopolysaccharide and capsular polysaccharide, both of which have been demonstrated to be able to induce humoral immunity. In this study, we investigated the effect of K. pneumoniae on epidermal cellular immunity, in vitro. The effects of K. pneumoniae on the maturation of Langerhans cells (LCs), the capacity to induce T-cell proliferation, and the secretion of interferon gamma (IFN-γ) by T cells were examined. The results showed that K. pneumoniae induced significant upregulation of CD86 and human leukocyte antigen-deterodimer (HLA-DR) levels on LCs, but not CD40 and CD80. K. pneumoniae-loaded LCs induced significant CD4 + and CD8 + T-cell proliferation. Significant increases in extracellular IFN-γ secretion by CD4 + and CD8 + T cells stimulated with K. pneumoniae-pulsed LCs using enzyme-linked immunospot assay (ELISPOT) were demonstrated, while only a part of the subjects showed increases in intracellular secretion of IFN-γ using intracellular staining assay. In sum, K. pneumoniae has the potential to enhance epidermal cellular immunity and may act as a potential adjuvant in intradermal vaccines designed to enhance cellular immunity.
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