Impaired thymic iNKT cell differentiation at early precursor stage in murine haploidentical bone marrow transplantation with GvHD.

Introduction: Early recovery of donor-derived invariant natural killer T (iNKT) cells are associated with reduced risk of graft-versus-host disease (GvHD) and overall survival. Patients with severe GvHD, however, had much slower iNKT cell reconstitution relative to conventional T cells.

Methods: To characterize the delay of iNKT cell reconstitution and explore its possible causes, we used a haploidentical bone marrow transplantation (haplo-BMT) mouse model with GvHD.

A wave of Foxp3 regulatory T cell accumulation in the neonatal liver plays unique roles in maintaining self-tolerance.

Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period. Regulatory T cells (Tregs) are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses. The features of Tregs in the neonatal liver under steady-state conditions are not well understood.

TRAF3IP3 at the trans-Golgi network regulates NKT2 maturation via the MEK/ERK signaling pathway.

Thymic natural killer T (NKT)2 cells are a subset of invariant NKT cells with PLZFGATA3IL-4. The differentiation of NKT2 cells is not fully understood. In the present study, we report an important role of TRAF3-interacting protein 3 (TRAF3IP3) in the functional maturation and expansion of committed NKT2s in thymic medulla.

PDCD5 regulates iNKT cell terminal maturation and iNKT1 fate decision.

Invariant natural killer T1 (iNKT1) cells are characterized by the preferential expression of T-box transcription factor T-bet (encoded by Tbx21) and the production of cytokine IFN-γ, but the relationship between the developmental process and iNKT1 lineage diversification in the thymus remains elusive. We report in the present study a crucial role of programmed cell death 5 (PDCD5) in iNKT cell terminal maturation and iNKT1 fate determination. Mice with T cell-specific deletion of PDCD5 had decreased numbers of thymic and peripheral iNKT cells with a predominantly immature phenotype and defects in response to α-galactosylceramide.

Newly Generated CD4 T Cells Acquire Metabolic Quiescence after Thymic Egress.

Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity.

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.

Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes.

Biosafety study and mechanism comparison on two types of silica with different nanostructures.

Silica is frequently used in oral drug delivery; however, its biosafety, particularly concerned with its nanostructure, has not been comprehensively studied yet. Here, the and biosafety of two types of silica (A200, nano-sized or micron-sized agglomerates; S350, micro-sized particles with nanopores) were compared and the possible reasons for the differences were explored. The results indicated that both A200 and S350 could inhibit the growth of Caco-2 cells by inducing apoptosis and changing the cell cycle progression.

Sorting of chromosomes on FACSAria(TM) SORP for the preparation of painting probes.

High purity chromosome sorting can be performed on instruments such as MoFlo MLS and BD influx, which are stream-in-air sorters equipped with water-cooled high power lasers. The FACSAria is a true fixed alignment, low laser powered instrument with a quartz flow cell gel-coupled to the collection optics. However, whether high purity mouse and human chromosomes can be obtained by sorting on the BD FACSAria(TM) Special Order Research Product (FACSAria SORP) remains to be determined.

Liver sinusoidal endothelial cells induce tolerance of autoreactive CD4+ recent thymic emigrants.

The liver is a unique lymphoid organ whose microenvironment is biased towards tolerance induction. We previously found that a proportion of CD4(+) autoreactive recent thymic emigrants (RTEs) retained in the liver after thymic egress and acquired IL-10 producing capability. To investigate the tolerance of these liver persisting CD4(+) RTEs in more detail and to study the liver stromal cell types that facilitate the tolerogenic changes in young T cells, the phenotype and function of liver RTEs were further characterized and the impact of liver sinusoidal endothelial cells (LSECs) and Kupffer cells on RTEs were examined using an in vitro co-culture system.

Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility.

The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition.

Retention and tolerance of autoreactive CD4(+) recent thymic emigrants in the liver.

Mechanisms of peripheral tolerance play a critical role in preventing T cells that escape from negative selection in the thymus from initiating autoimmune reactions. To investigate the site of peripheral tolerance induction, we examined migration and activation of recent thymic emigrants (RTEs) in liver, spleen, lymph node and peripheral blood. We show that a fraction of RTE precursors were retained in the liver independent of the secondary lymphoid organs.

Lidamycin regulates p53 expression by repressing Oct4 transcription.

Antitumor antibiotic lidamycin (LDM) is widely used in the treatment of a variety of cancers. Here we demonstrated that LDM up-regulates the expression of the tumor suppressor p53 gene by repressing Oct4 transcription. We showed that low dose LDM-induced increase of p53 expression and decrease of Oct4 expression in P19 and HCT116-p53(+/+) cells.

Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice.

The senescence accelerated mouse prone 8 substrain (SAM-P8), widely accepted as an animal model for studying aging and antiaging drugs, was used to examine the effects of dietary supplementation with extracts of Cistanche deserticola (ECD) which has been used extensively in traditional Chinese medicine because of its perceived ability to promote immune function in the elderly. Eight-month-old male SAM-P8 mice were treated with ECD by daily oral administrations for 4 weeks. The results showed that dietary supplementation of 150 mg/kg and 450 mg/kg of ECD could extend the life span measured by Kaplan-Meier survival analysis in dose-dependent manner.

Changes of cytokines during a spaceflight analog--a 45-day head-down bed rest.

Spaceflight is associated with deregulation in the immune system. Head-down bed rest (HDBR) at -6° is believed to be the most practical model for examining multi-system responses to microgravity in humans during spaceflight. In the present study, a 45-day HDBR was performed to investigate the alterations in human immune cell distributions and their functions in response to various stimuli.

Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure.

Background: Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research.

Objectives: Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared.

Methods: In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity.

The reduction of tumor interstitial fluid pressure by liposomal imatinib and its effect on combination therapy with liposomal doxorubicin.

Interstitial fluid pressure (IFP) in tumor is much higher than that in normal tissue and it constitutes a great obstacle for the delivery of chemodrugs, which makes it a potential target for cancer therapy. In this study, imatinib, a molecular targeting drug, was loaded in sterically stabilized liposomes (SSL-IMA) to reduce the tumor IFP, in an attempt to deliver more liposomal doxorubicin (SSL-DOX) into tumor tissue. In a mouse B16 melanoma model, intravenous injection of 20 mg/kg SSL-IMA achieved the most reduction of tumor IFP and the effect lasted for at least 50 h with the least hematotoxicity.

A specific peptide ligand-modified lipid nanoparticle carrier for the inhibition of tumor metastasis growth.

Tumor metastasis accounts for 90% of cancer-associated deaths and is almost inaccessible by chemotherapy, surgical operation or radiotherapy. Here, a tumor metastasis-specific nanocarrier system has been constructed by modification of stealth lipid nanoparticles with a specific peptide ligand. Highly metastatic breast cancer MDA-MB-231 that stably expressed luciferase (MDA-MB-231/Luc) was used as tumor cell model.

The use of a tumor metastasis targeting peptide to deliver doxorubicin-containing liposomes to highly metastatic cancer.

Tumor metastasis is responsible for 90% of cancer-associated deaths and highly metastatic cancers are more prone to form metastasis foci and acquire the drug resistance. Here, a nanocarrier system (TMT-LS) has been constructed by modification of stealth liposomes with a metastatic cancer specific peptide, using the unmodified stealth liposomes (LS) as the control. The active targeted nanocarriers presented satisfactory particle size (about 100 nm) and drug release characteristics in vitro.

LyGDI is a promising biomarker for ovarian cancer.

Introduction: LyGDI is an inhibitor of Rho protein activation by blocking its transformation between guanosine 5'-diphosphate- and guanosine 5'-triphosphate-bound states. The aim of this study was to investigate the usefulness of LyGDI as a biomarker for the detection of ovarian cancer, and its specificity and sensitivity were compared with those of cancer antigen 125 (CA125).

Methods: The serum levels of LyGDI were determined by enzyme-linked immunosorbent assay in 42 patients with ovarian disease, including 30 ovarian cancers and 12 benign ovarian lesions, and 76 healthy controls.

Hemokinin-1 activates the MAPK pathway and enhances B cell proliferation and antibody production.

Hemokinin 1 (HK-1) is a substance P-like tachykinin peptide predominantly expressed in non-neuronal tissues. In addition to a prominent function in lymphoid development, recent studies indicate a potential role for HK-1 in immunoregulation. The current study was focused on its action on mature B cells.

Expression of vascular endothelial growth factor and E26 transformation-specific-1 in breast carcinoma.

Objective: To study the expression of vascular endothelial growth factor (VEGF) and transcription factor E26 transformation-specific-1 (ETS-1) in breast carcinoma and its effect on angiogenesis, tumor invasion and metastasis.

Methods: In situ hybridization and immunohistochemistry (streptomycin avidin-biotin-peroxidase complex, SP) were used to detect the mRNA and protein expression of VEGF and ETS-1 in breast carcinoma.

Results: VEGF mRNA and its protein were highly expressed in tumor cells of breast carcinoma.

[Expression of vascular endothelial growth factor and its receptor (Flt-1) in breast carcinoma].

Objective: To investigate the expression of vascular endothelial cell growth factor (VEGF) and its receptor (Flt-1) in breast carcinoma and the relationship of such expression with angiogenesis, tumor invasion and metastasis.

Methods: In situ hybridization and immunohistochemistry technique were used to test the expression of mRNA and protein expression of VEGF and flt-1 in 48 specimens of breast carcinoma. 48 specimens of tissues near cancer, 3 specimens of fibroadenoma of breast, and 3 specimens of normal breast were used as controls.