Accurate combined preoperative localization of insulinomas is useful of the choice of enucleation, eliminates the need for blind distal pancreatectomy and avoids re-operation. Whenever possible, a pancreas-sparing approach such as enucleation should be adopted.

This study assessed the effects of leukemia-related protein 16 (LRP16) on the regulation of pancreatic functions in mouse insulinoma (MIN6) cells. Cells with down-regulated expression of LRP16 were obtained by a shRNA interference strategy. Insulin content and glucose-stimulated insulin secretion (GSIS) were examined by radioimmunoassay. Western blotting was applied to detect protein expression. Glucose-stimulated sub-cellular localization of PDX-1 was immunocytochemically determined. Cell proliferation and apoptosis were detected by flow cytometry. Our results showed that LRP16 regulated insulin content in MIN6 cells by controlling expression of insulin and insulin transcription factors. LRP16 gene silence in MIN6 cells led to reduced cell proliferation and increased apoptosis. The observation of phosphorylation of serine-473 Akt and the localization of PDX-1 to the nucleus under glucose-stimulation exhibited that LRP16 was a component mediating Akt signaling in MIN6 cells. These results suggest that LRP16 plays a key role in maintaining pancreatic β-cell functions and may help us to understand the protective effects of estrogen on the functions of pancreatic β-cells.

Objectives. Fatty liver disease (FLD) is strongly linked to the occurrence of type 2 diabetes mellitus (T2DM). Insulin resistance (IR) is linked to smoking. Our study’s purpose was to see how smoking and fatty liver accompanied affected the development of T2DM in the past. Materials and Methods. We collected data from 15,464 Japanese adults aged 18 to 79 years who took part in the NAGALA research, and our team utilized a Cox proportion risk model to look at the combination effect of FLD and smoking status on the incidence of T2DM. Participants were separated into three categories: nonsmokers, ex-smokers, and current smokers. An abdominal ultrasound was used to diagnose FLD. Results. 384 subjects had T2DM after a median follow-up of 5.4 years. In comparison to the other groups, current FLD smokers had a greater chance of developing T2DM. Ex-smokers and present FLD smokers, on the other hand, had no significant difference in their likelihood of acquiring T2DM. When compared to ex-smokers and nonsmokers without FLD, current smokers with FLD had a considerably greater chance of acquiring T2DM. Furthermore, the risk of T2DM among nonsmokers, ex-smokers with FLD, and current smokers without FLD was not statistically significant. Conclusions. In order to prevent the progression of T2DM, we should recognize that smoking status may vary in FLD.

Objectives To evaluate the anti-tumor activities of CD20/HLA-DR CrossmabCH1-CL through cell and animal models. Methods Based on “knobs-into-holes” and “crossover” technology, CrossMab, targeting CD20 and HLA-DR, was constructed. A binding assay and a competitive inhibition assay were performed to confirm its specificity. The effects of CrossMab on antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity were measured. Cell apoptosis, lysosome-mediated cell death, and lysosomal permeability were quantified. In addition, the effects of CrossMab on peripheral blood leukocytes were tested. The pharmacokinetics were determined with a noncompartmental analysis model. Human malignant lymphoma xenograft models in CB17-SCID mice were established for an in-vivo efficacy study. Results The antitumor activities of CrossMab were shown both in vitro and in vivo. CrossMab exhibited strong binding to CD20 and HLA-DR at the same time in Raji cells. CrossMab also demonstrated antilymphoma effects by inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Furthermore, CrossMab altered the lysosomal membrane permeability. The toxicity of CrossMab on normal peripheral blood lymphocytes (PBLs) was specific to B cells. A mouse xenograft model demonstrated the antitumor activities of CrossMab in vivo. Conclusions CrossMab exhibited an enhanced antigen recognition ability and antitumor activities in lymphoma without evident toxicity. CrossMab could be an effective immunotherapeutic strategy for non-Hodgkin lymphoma.