Exploring the potential of the TCR repertoire as a tumor biomarker (Review).

T cells play an important role in adaptive immunity. Mature T cells specifically recognize antigens on major histocompatibility complex molecules through T-cell receptors (TCRs). As the TCR repertoire is highly diverse, its analysis is vital in the assessment of T cells. Advances in sequencing technology have provided convenient methods for further investigation of the TCR repertoire. In the present review, the TCR structure and the mechanisms by which TCRs function in tumor recognition are described. In addition, the potential value of the TCR repertoire in tumor diagnosis is reviewed. Furthermore, the role of the TCR repertoire in tumor immunotherapy is introduced, and the relationships between the TCR repertoire and the effects of different tumor immunotherapies are discussed. Based on the reviewed literature, it may be concluded that the TCR repertoire has the potential to serve as a biomarker for tumor prognosis. However, a wider range of cancer types and more diverse subjects require evaluation in future research to establish the TCR repertoire as a biomarker of tumor immunity.

The Ankyrin Repeat Domain 49 (ANKRD49) Augments Autophagy of Serum-Starved GC-1 Cells through the NF-κB Pathway.

The ankyrin repeat domain 49 (ANKRD49) is an evolutionarily conserved protein highly expressed in testes. However, the function of ANKRD49 in spermatogenesis is unknown. In this study, we found that ANKRD49 resides primarily in nucleus of spermatogonia, spermatocytes and round spermatids. ANKRD49 overexpression augments starvation-induced autophagy in male germ GC-1 cells whereas shRNA knockdown of ANKRD49 attenuates the autophagy. Inhibition of NF-κB pathway by its inhibitors or p65 siRNA prevents the ANKRD49-dependent autophagy augmentation, demonstrating that ANKRD49 enhances autophagy via NF-κB pathway. Our findings suggest that ANKRD49 plays an important role in spermatogenesis via promotion of autophagy-dependent survival.

Partial protective effect of intranasal immunization with recombinant Toxoplasma gondii rhoptry protein 17 against toxoplasmosis in mice.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects a variety of mammals, including humans. An effective vaccine for this parasite is therefore needed. In this study, RH strain T. gondii rhoptry protein 17 was expressed in bacteria as a fusion with glutathione S-transferase (GST) and the recombinant proteins (rTgROP17) were purified via GST-affinity chromatography. BALB/c mice were nasally immunised with rTgROP17, and induction of immune responses and protection against chronic and lethal T. gondii infections were investigated. The results revealed that mice immunised with rTgROP17 produced high levels of specific anti-rTgROP17 IgGs and a mixed IgG1/IgG2a response of IgG2a predominance. The systemic immune response was associated with increased production of Th1 (IFN-γand IL-2) and Th2 (IL-4) cytokines, and enhanced lymphoproliferation (stimulation index, SI) in the mice immunised with rTgROP17. Strong mucosal immune responses with increased secretion of TgROP17-specific secretory IgA (SIgA) in nasal, vaginal and intestinal washes were also observed in these mice. The vaccinated mice displayed apparent protection against chronic RH strain infection as evidenced by their lower liver and brain parasite burdens (59.17% and 49.08%, respectively) than those of the controls. The vaccinated mice also exhibited significant protection against lethal infection of the virulent RH strain (survival increased by 50%) compared to the controls. Our data demonstrate that rTgROP17 can trigger strong systemic and mucosal immune responses against T. gondii and that ROP17 is a promising candidate vaccine for toxoplasmosis.

Intranasal immunisation of the recombinant Toxoplasma gondii receptor for activated C kinase 1 partly protects mice against T. gondii infection.

Nasal vaccination is an effective therapeutic regimen for preventing certain infectious diseases. The mucosal immune response is important for resistance to Toxoplasma gondii infection. In this study, we evaluated the immune responses elicited in BALB/c mice by nasal immunisation with recombinant T. gondii receptor for activated C kinase 1 (rTgRACK1) and their protective efficacy against T. gondii RH strain during both chronic and lethal infections. Nasal vaccination with rTgRACK1 increased the level of secretory IgA in nasal, intestinal and vesical washes, and the level of IFN-γ and IL-2 in intestinal washes, indicating that rTgRACK1 vaccination promotes mucosal immune responses. The mice immunised with rTgRACK1 also displayed increased levels of rTgRACK1-specific IgA, total IgG, IgG1 and in particular IgG2a in their blood sera, increased production of IFN-γ, IL-2 and IL-4 but not IL-10 from their isolated spleen cells, and enhanced splenocyte proliferation in vitro. rTgRACK1-vaccinated mice were effectively protected against infection with T. gondii RH strain, showing over 50% reduction of tachyzoite burdens in their liver and brain tissues during a chronic infection, and also a 45% increase in their survivals during a lethal challenge. These results indicate that rTgRACK1 might represent an intriguing immunogen for developing a mucosal vaccine against toxoplasmosis.

Mesenchymal stem cells in the treatment of pediatric diseases.

BACKGROUND: In recent years, the incredible interests in mesenchymal stem cells have boosted the expectations of both patients and physicians. Unlike embryonic stem cells, neither their procurement nor their use is deemed controversial. Moreover, their immunomodulatory capacity coupled with low immunogenicity has opened up their allogenic use, consequently broadening the possibilities for their application. In May 2012, Canadian health regulators approved Prochymal, the first mesenchymal stem cells-based drug, for acute graft-versus-host diseases in children who have failed to respond to steroid treatment. The aim of this article is to review the recent advances in mesenchymal stem cells for pediatric diseases. DATA SOURCES: A literature review was performed on PubMed from 1966 to 2013 using the MeSH terms "mesenchymal stem cells", "clinical trials" and "children". Additional articles were identified by a hand search of the references list in the initial search. RESULTS: The following categories are described: general properties, mechanisms of action, graft-versus-host diseases, cardiovascular diseases, liver diseases, inflammatory bowel diseases, osteoarticular diseases, autoimmune diseases, type 1 diabetes, and lung diseases. CONCLUSIONS: Mesenchymal stem cells, owing to their availability, immunomodulatory properties, low immunogenicity, and therapeutic potential, have become one of the most attractive options for the treatment of a wide range of diseases. It is expected to see more and more clinical trials and applications of mesenchymal stem cells for pediatric diseases in the near future.

[The use of diammonium glycyrrhizinate in the treatment of hepatic dysfunction in burn patients].

OBJECTIVE: To observe the protective effect of diammonium glycyrrhizinate on hepatic function in burn patients. METHODS: Twenty burn patients with hepatic dysfunction were enrolled in the study and were randomly divided into 2 groups, i. e. treatment (T, n = 10, with conventional treatment and intravenous infusion of 150 mg diammonium glycyrrhizinate per day for 14 days), and control (C, n = 10, with conventional treatment) groups. The blood samples in both groups were collected before and 7 and 15 days after the treatment. The serum contents of ALT, AST, GGT, ALP and PA in the blood samples were determined and analyzed comparatively. RESULTS: There was obvious difference in the serum contents of ALT, AST, GGT, ALP and PA in the T group before treatment (168 +/- 46 U/L, 104 +/- 29 U/L, 162 +/- 37 U/L, 149 +/- 17 U/L, 310 +/- 35 mg/L, respectively) and 15 days after treatment (51 +/- 9 U/L, 31 +/- 3 U/L, 56 +/- 10 U/L, 103 +/- 9 U/L, 372 +/- 44 mg/L, respectively, P < 0.05). There was no difference in these indices in the C group before and after treatment (P > 0.05). CONCLUSION: Diammonium glycyrrhizinate seemed to be beneficial to the management of postburn hepatic dysfunction with obvious rapid depression of hepatic enzymes.