Regenerating genes (Reg) have been found during the search for factors involved in pancreatic islet regeneration. Our recent study discovered that pancreatic β-cell-specific overexpression of Reg3β protects against streptozotocin (Stz) -induced diabetes in mice. To investigate its potential roles in the treatment of diabetes, we produced a recombinant Reg3β protein and provided evidence that it is active in promoting islet β-cell survival against Stz- triggered cell death. Though ineffective in alleviating preexisting diabetes, pretreatment of recombinant Reg3β was capable of minimizing the Stz-induced hyperglycemia and weight loss, by preserving serum and pancreatic insulin levels, and islet β-cell mass. No obvious changes were observed in the rate of cell proliferation and hypertrophy in α- or acinar-cells after treatment with recombinant Reg3β. The underlying mechanism of Reg3β-mediated protection seems to involve Akt activation which upregulates Bcl-2 and Bcl-xL levels and consequently promotes cell survival.

Progressive loss and dysfunction of islet β-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rReg3α) and proved that it protects against acute pancreatitis in mice. Whether rReg3α protects islet β-cells in diabetes has been elusive. In the present study, rReg3α stimulated MIN6 cell proliferation and resisted STZ-caused cell death. The protective effect of rReg3α was also found in mouse primary islets. In BALB/c mice, rReg3α administration largely alleviated STZ-induced diabetes by the preservation of β-cell mass. The protective mechanism could be attributed to Akt/Bcl-2/-xL activation and GRP78 upregulation. Scattered insulin-expressing cells and clusters with small size, low insulin density, and exocrine distribution were observed and considered to be neogenic. In isolated acinar cells with wheat germ agglutinin (WGA) labeling, rReg3α treatment generated insulin-producing cells through Stat3/Ngn3 signaling, but these cells were not fully functional in response to glucose stimulation. Our results demonstrated that rReg3α resists STZ-induced β-cell death and promotes β-cell regeneration. rReg3α could serve as a potential drug for β-cell maintenance in anti-diabetic treatment.

Despite decades of control efforts, the prevalence of schistosomiasis remains high in many endemic regions, posing significant challenges to global health. One of the key factors contributing to the persistence of the disease is the complex life cycle of the Schistosoma parasite, the causative agent, which involves multiple stages of development and intricate interactions with its mammalian hosts and snails. Among the various stages of the parasite lifecycle, the deposition of eggs and their migration through host tissues is significant, as they initiate the onset of the disease pathology by inducing inflammatory reactions and tissue damage. However, our understanding of the mechanisms underlying Schistosoma egg extravasation remains limited, hindering efforts to develop effective interventions. Microphysiological systems, particularly organ-on-a-chip systems, offer a promising approach to study this phenomenon in a controlled experimental setting because they allow the replication of physiological microenvironments in vitro. This review provides an overview of schistosomiasis, introduces the concept of organ-on-a-chip technology, and discusses its potential applications in the field of schistosomiasis research.

Background Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells, resulting in insulin deficiency and hyperglycemia. Existing insulin therapies manage symptoms but do not fully stabilize blood glucose levels. Schistosoma mansoni infection or its eggs inhibit T1D in rodent models. This study evaluated the antidiabetic effects of Schistosoma mansoni-derived soluble egg antigen (SEA) and glycoproteins (IPSE and Omega-1) in a streptozotocin-induced diabetic rat model. Methods Glycoproteins were designed using in silico methods and synthesized following epitope prediction, antigenicity assessment, and molecular docking analysis. These glycoproteins were administered at doses of 50 μg and 100 μg per rat in a stratified randomized trial comprising eight treatment groups and two control groups, each containing five streptozotocin-induced diabetic rats: SEA (A-B), Omega-13 (C-D), IPSE2-3 (E-H), insulin-only (I), and PBS (J). Blood glucose, weight, IFN-γ, IL-4 levels, and pancreatic histology were assessed. Results In silico analysis of IPSE and Omega-1 showed strong antigenicity (epitopes >0.60), binding energies from -7.9 to -11.9 Kcal/mol, molecular weights of 1261.40–2034.30 Da, and theoretical pI of 8.23–9.70. In vivo, IPSE and Omega-1 significantly reduced glucose (from 5.76–26.16 mmol/L to 3.94–18.92 mmol/L, p < 0.05), promoted weight gain (192.3–235 g to 231.3–250.2 g), and caused mild-moderate pancreatic infiltration. Conclusions These findings suggest that SEA, IPSE, and Omega-1 are promising candidates for novel diabetes therapies, warranting further investigations.