FAP deficiency enhances thermogenesis and attenuates metabolic inflammation in diet-induced obesity.

Objective: Fibroblast activation protein α (FAP) is expressed in normal adipose tissue and related to some pleiotropic metabolic regulators. However, the exact role and mechanism of FAP in obesity and related metabolic disorders are not well understood.

Methods: FAP knockout mice were fed a normal diet or a high-fat diet (HFD) for 12 weeks.

Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in -infected mice.

This study aimed to investigate the relationship between interleukin (IL)-35 level and IL-35-producing regulatory T cells (iTr35 subset) in (Mtb)-infected mice. After the mice were injected with Mtb strain H37R via tail vein, the bacterial burden, lung lesions, and the impact of immune suppression on the infected mice were respectively assessed. The results, when compared with the control mice, showed that the mRNA expression levels of the p35 and Epstein-Barr virus-induced gene 3 of IL-35 were significantly increased in the Mtb-infected mouse spleen at 4 or 8 weeks post-infection and their protein expression levels were concurrently increased in the lungs of the mice, especially in 8 week infected mice.

Antitumor efficacy induced by a B16F10 tumor cell vaccine treated with mitoxantrone alone or in combination with reserpine and verapamil in mice.

An apoptotic tumor cell serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. In the present study, a B16F10 tumor cell vaccine treated with mitoxantrone (MIT) was developed, and its antitumor effect on mice was evaluated. The results indicated that the B16F10 tumor cell vaccine treated with MIT alone or in combination with reserpine (RP) and verapamil (VP) for 12 h triggered apoptosis, and that the expression of CD80, the MHC II class molecule, NKG2D and its ligand were significantly increased compared to the expression levels in the control group.

Antitumor efficacy of viable tumor vaccine modified by heterogenetic ESAT-6 antigen and cytokine IL-21 in melanomatous mouse.

The goal of this study was to investigate whether glycosylphosphatidylinositol (GPI)-anchored 6 kDa early secreted antigenic target (ESAT-6) and IL-21-producing B16F10/ESAT-6-GPI-IL-21 viable vaccine would induce antitumor efficacy. Mice were immunized with B16F10/ESAT-6-GPI-IL-21 vaccine and challenged by B16F10 cells 2 weeks later. Antitumor efficacy and mechanisms of the vaccine were analyzed.

Nanoparticle-based adjuvant for enhanced protective efficacy of DNA vaccine Ag85A-ESAT-6-IL-21 against Mycobacterium tuberculosis infection.

Unlabelled: The goal of this study was to evaluate the protective efficacy of a cationic nanoparticle-based DNA vaccine expressing antigen 85A (Ag85A) and 6-kDa early secretory antigen target (ESAT-6) of Mycobacterium tuberculosis as well as cytokine interleukin-21 (IL-21) against M. tuberculosis infection. The results of this indicated that the anti-M.

Human umbilical blood mononuclear cell-derived mesenchymal stem cells serve as interleukin-21 gene delivery vehicles for epithelial ovarian cancer therapy in nude mice.

Ovarian cancer causes more deaths than any other cancer of the female reproductive system, and its overall cure rate remains low. The present study investigated human umbilical blood mononuclear cell (UBMC)-derived mesenchymal stem cells (UBMC-MSCs) as interleukin-21 (IL-21) gene delivery vehicles for ovarian cancer therapy in nude mice. MSCs were isolated from UBMCs and the expanded cells were phenotyped by flow cytometry.

Immunization with DNA vaccine expressing herpes simplex virus type 1 gD and IL-21 protects against mouse herpes keratitis.

The development of novel vaccines to eradicate herpes simplex virus (HSV) is a global public health priority. In this study, we developed a DNA vaccine expressing HSV-1 glycoprotein D (gD) and mouse interleukin-21(IL-21) and intramuscularly inoculated mice 3 times at 2-week intervals with a total of 300 ?g/mouse. Two weeks after the last immunization the specific antibody, splenocyte proliferative response to gD, IFN-? and IL-4 as well as the cytotoxic activities of splenocytes and natural killer (NK) cells were assayed.

An ocular mucosal administration of nanoparticles containing DNA vaccine pRSC-gD-IL-21 confers protection against mucosal challenge with herpes simplex virus type 1 in mice.

Herpes stromal keratitis (HSK) is a chronic inflammatory process caused by the infection of herpes simplex virus type 1 (HSV-1). Development of a HSV-1 vaccine is a priority because these infections are common and cannot be well prevented. It appears that the potential of nanocarriers in DNA vaccination will be required to augment the immune response to DNA vaccines.

Augmenting therapy of ovarian cancer efficacy by secreting IL-21 human umbilical cord blood stem cells in nude mice.

In the present study, CD34(+) human umbilical cord blood stem cells (UCBSCs) were engineered to express interleukin-21 (IL-21) and then were transplanted into A2780 ovarian cancer xenograft-bearing Balb/c nude mice. The therapeutic efficacy of this procedure on ovarian cancer was evaluated. The findings from the study indicated that UCBSCs did not form gross or histological teratomas until up to 70 days postinjection.

Enhancing therapy of B16F10 melanoma efficacy through tumor vaccine expressing GPI-anchored IL-21 and secreting GM-CSF in mouse model.

In the present study, we developed the tumor vaccine expressing IL-21 in the GPI-anchored form together with secreting GM-CSFs and investigated its antitumor efficacy in C57BL/6 mouse model. The fusion genes containing IL-21 and the GPI anchor signal sequence were acquired by overlaping PCR, inserted into the downstream of two multi-clone sites in recombinant plasmid pRSC/GM-CSFs to form pRSC/IL-21-gpi-GM-CSFs that was transfected into the B16F10 cells. The tumor cell vaccine B16F10/IL-21-gpi-GM-CSFs was identified by reverse transcription PCR, IFA and FCM, respectively.

Investigation of immunogenic effect of the BCG priming and Ag85A- GM-CSF boosting in Balb/c mice model.

Mycobacterium tuberculosis (M. tuberculosis) has once again become a major public health threat owing to the combined effects of a worldwide anti-tuberculosis drug resistance and the emergence of the human immunodeficiency virus pandemic. The Bacille Calmette-Guérin (BCG)-based vaccine has displayed inconsistent efficacy in different trials although it continues to be used to prevent tuberculosis in many countries.