T lymphocyte characteristics and immune repertoires in the epicardial adipose tissue of heart failure patients.

Background: Epicardial adipose tissue (EAT) acts as an active immune organ and plays a critical role in the pathogenesis of heart failure (HF). However, the characteristics of immune cells in EAT of HF patients have rarely been elucidated. Methods: To identify key immune cells in EAT, an integrated bioinformatics analysis was performed on public datasets. EAT samples with paired subcutaneous adipose tissue (SAT), heart, and peripheral blood samples from HF patients were collected in validation experiments. T cell receptor (TCR) repertoire was assessed by high-throughput sequencing. The phenotypic characteristics and key effector molecules of T lymphocytes in EAT were assessed by flow cytometry and histological staining. Results: Compared with SAT, EAT was enriched for immune activation-related genes and T lymphocytes. Compared with EAT from the controls, activation of T lymphocytes was more pronounced in EAT from HF patients. T lymphocytes in EAT of HF patients were enriched by highly expanded clonotypes and had greater TCR clonotype sharing with cardiac tissue relative to SAT. Experiments confirmed the abundance of IFN-γ+ effector memory T lymphocytes (TEM) in EAT of HF patients. CCL5 and GZMK were confirmed to be associated with T lymphocytes in EAT of HF patients. Conclusion: EAT of HF patients was characterized by pronounced immune activation of clonally expanded IFN-γ+ TEM and a generally higher degree of TCR clonotypes sharing with paired cardiac tissue.

Calcium carbonate end-capped, folate-mediated Fe3O4@mSiO2 core-shell nanocarriers as targeted controlled-release drug delivery system.

Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was modified with cancer cell-specific ligand folic acid. Calcium carbonate was then employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely, MMSN-FA-CaCO3. The formation of the MMSN-FA-CaCO3 was proved by several characterization techniques, viz. transmission electron microscopy, zeta potential measurement, Fourier transform infrared spectroscopy, BET surface area measurement, and UV-Vis spectroscopy. Daunomycin was successfully loaded in the MMSN-FA-CaCO3 and the system exhibited sensitive pH stimuli-responsive release characteristics under blood or tumor microenvironment. Cellular uptake by folate receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO3 was higher than that by non-folated-conjugated ones. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR-negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate of MMSN-FA-DNM-CaCO3 to HeLa cells. The present data suggest that the CaCO3 coating and folic acid modification of MMSN are able to create a targeted, pH-sensitive template for drug delivery system with application in cancer therapy.

[Autologous bone marrow stem cell transplantation for treatment terminal liver diseases].

OBJECTIVE: To evaluate the effect of autologous bone marrow-derived stem cell (BMSCs) transplantation in the treatment of liver failure and decompensated hepatic cirrhosis. METHODS: Bone marrow was harvested (65-95 ml) from 24 patients in the transplantation group. The BMSCs were isolated and infused into liver or spleen of patients via hepatic or splenic artery. At different time points after the transplantation, the patients' liver function and prothrombin time (PT) were evaluated, and the survival rate and symptoms of the patients were recorded. RESULTS: All the serum biochemical indexes remained stable 2 weeks after the transplantation, and at 4 weeks after transplantation, albumin level increased significantly in comparison with the preoperative level (P<0.05). At 12 weeks, the albumin level further increased (P<0.01) along with Pre-ALB (P<0.01), while total bilirubin, tolal bile acid, PT and fibrinogen were all significantly lowered (P<0.05), and globulin, ALT, and AST remained unchanged (P>0.05). One week after the transplantation, improved appetite was observed in 22 cases (91.67%), and 21 cases (87.5%) showed better physical strength; at 2 weeks, hepatic face improved in 15 cases (62.5%), and spider telangiectasia was significantly reduced in one case; at 12 weeks, the survival rate of the patients was 62.5%, and 9 died or gave up treatment due to chronic liver failure complicated by spontaneous bacterial peritonitis, hepatorenal syndrome, or DIC. No complications associated with the transplantation occurred in these patients. CONCLUSION: BMSC transplantation can significantly improve the liver function of patients with terminal liver disease with good safety and effectiveness.