Analysis of immune response in BALB/c mice immunized with recombinant plasmids pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3 of Taenia solium.

There is a lack of vaccine against human cysticercosis, thus making a huge population at the risk of infection. In this study, we chose a novel potential antigen molecule Taenia solium 14-3-3.3 (Ts14-3-3.3) and optimized it as sp-Ts14-3-3.3 (sp is immunoglobulin H chain V-region precursor, partial) in order to construct recombinant plasmids pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3. BALB/c mice were divided into four groups for immunization: pMZ-X3-Ts14-3-3.3, pMZ-X3-sp-Ts14-3-3.3, pMZ-X3 plasmid control group and PBS control group. Compared with two control groups, the proliferation level of splenic lymphocytes increased significantly in pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3 groups and reached the maximum in week 6. And the same case arose as cytokines associated with Th1 response, IFN-γ, and IL-2 while those with Th2 response, IL-4, IL-10 went up and reached the maximum in week 4. The levels of serum specific IgG, IgG1 and IgG2a rose and reached the maximum in week 6, 4 and 6, respectively. Meanwhile, the proportion of CD4+/CD8+ splenic T lymphocytes increased and reached the peak in week 6. The results indicated that the recombinant plasmids pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3 can induce specific cellular and humoral immune responses in BALB/c mice with immunization. Notably, the recombinant plasmid pMZ-X3-sp-Ts14-3-3.3 has a better immune effect, which proves that Ts14-3-3.3 enjoys a higher possibility as a potential antigen molecule to T. solium vaccine.

Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction.

Obesity is an important risk factor for cardiovascular disease, diabetes and certain cancers. The fat mass- and obesity-associated (FTO) gene is tightly associated with the pathophysiology of obesity, whereas the exact role of FTO remains poorly understood. Here, we investigated the alternations of FTO mRNA and protein expression in the peripheral metabolic tissues and the brain upon energy restriction (ER) and explored the involvement of the leptin signaling pathway in FTO regulation under ER status. ER decreased the FTO mRNA and protein expression in hypothalamus and brainstem but not in periphery. Using double-immunofluorescence staining, FTO was found to be colocalized with the leptin receptor long isoform (LepRb) in arcuate nucleus of hypothalamus and the nucleus of the solitary tract. In LepRb mutant db/db mice, the FTO downregulation in brain and body weight reduction induced by ER were completely abolished. The enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by ER was also impaired in db/db mice. Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice. Thus, our results provide the first evidence that the LepRb-STAT3 signaling pathway is involved in the brain FTO downregulation during ER.

Impact of total variation regularized expectation maximization reconstruction on the image quality of 68Ga-PSMA PET: a phantom and patient study.

OBJECTIVES: To investigate the impact of total variation regularized expectation maximization (TVREM) reconstruction on the image quality of 68Ga-PSMA-11 PET/CT using phantom and patient data. METHODS: Images of a phantom with small hot sphere inserts and 20 prostate cancer patients were acquired with a digital PET/CT using list-mode and reconstructed with ordered subset expectation maximization (OSEM) and TVREM with seven penalisation factors between 0.01 and 0.42 for 2 and 3 minutes-per-bed (m/b) acquisition. The contrast recovery (CR) and background variability (BV) of the phantom, image noise of the liver, and SUVmax of the lesions were measured. Qualitative image quality was scored by two radiologists using a 5-point scale (1-poor, 5-excellent). RESULTS: The performance of CR, BV, and image noise, and the gain of SUVmax was higher for TVREM 2 m/b groups with the penalization of 0.07 to 0.28 compared to OSEM 3 m/b group (all p < 0.05). The image noise of OSEM 3 m/b group was equivalent to TVREM 2 and 3 m/b groups with a penalization of 0.14 and 0.07, while lesions' SUVmax increased 15 and 20%. The highest qualitative score was attained at the penalization of 0.21 (3.30 ± 0.66) for TVREM 2 m/b groups and the penalization 0.14 (3.80 ± 0.41) for 3 m/b group that equal to or greater than OSEM 3 m/b group (2.90 ± 0.45, p = 0.2 and p < 0.001). CONCLUSIONS: TVREM improves lesion contrast and reduces image noise, which allows shorter acquisition with preserved image quality for PSMA PET/CT. ADVANCES IN KNOWLEDGE: TVREM reconstruction with optimized penalization factors can generate higher quality PSMA-PET images for prostate cancer diagnosis.