Objective:Increased oxidative stress is associated with the progression of diabetic mellitus. In the present study, we investigated the effects of the ethanolic extract of Nigerian propolis (N. propolis) on markers of oxidative stress, histology of the liver and pancreas and glycaemia in alloxan-induced diabetic rats.Materials and Methods:Alloxan-induced hyperglycemic Wistar rats were treated with either metformin (150 mg/kg/d) or N. propolis (200 mg/kg/d and 300 mg/kg/d) for 28 days. At the end of the treatment period, the rats were sacrificed; blood was collected for biochemical analysis while their pancreases and liver were excised and processed for histological studies.Results:Serum oxidative stress markers and blood glucose concentration were compared between the treated and control rats. In contrast to the non-treated diabetic rats, blood glucose concentration were not significantly different between treated rats and control (P < 0.05) at 28 days of treatment with N. propolis and metformin. Serum malondialdehyde levels was reduced while superoxide dismutase levels were elevated in the N. propolis group; these levels were converse in the diabetic group, these differences are statistically significant (P<0.05) when compared with the control. Histologically, there was improvement in the treated group compared to the untreated group.Conclusion:These findings suggest that the N. propolis confers protection against hyperglycemia-induced oxidative stress in both liver and pancreas of adult Wistar rats.

The primary cilium is a tiny cell protrusion known to transduce key extracellular signals, including those of the sonic hedgehog pathway, which activates Gli transcription factors for various cellular functions. To understand the significance of the Gli2 transcription factor in fibroblasts, we establish a Gli2-knockout NIH3T3 cell line by CRISPR/ Cas9 technology. Surprisingly, NIH3T3 fibroblasts lacking Gli2 expression through gene knockout or RNA interference possess longer primary cilia after stimulation of ciliogenesis by serum starvation. This lengthening of primary cilia is associated with enhanced autophagy-mediated Ofd1 degradation, and can be reversed by pharmacological and genetic inhibition of autophagy. Meanwhile, flow cytometry reveals that Gli2 −/− NIH3T3 fibroblasts exhibit a delay in cell cycle re-entry after serum re-stimulation. Ablation of their primary cilia through Kif3a knockdown rescues the delay in cell cycle re-entry. These results suggest that Gli2 plays an unexpected role in cell cycle re-entry through an autophagy-mediated regulation on ciliary length in fibroblasts.

Transthyretin amyloidosis (ATTR amyloidosis) is a fatal systemic disease caused by amyloid deposits of misfolded transthyretin, leading to familial amyloid polyneuropathy and/or cardiomyopathy, or a rare oculoleptomeningeal amyloidosis. A good model system that mimic the disease phenotype is crucial for the development of drugs and treatments for this devastating degenerative disorder. The present models using fruit flies, worms, rodents, non-human primates and induced pluripotent stem cells have helped researchers understand important disease-related mechanisms and test potential therapeutic options. However, the challenge of creating an ideal model still looms, for these models did not recapitulates all symptoms, particularly neurological presentation, of ATTR amyloidosis. Recently, knock-in techniques was used to generate two humanized ATTR mouse models, leading to amyloid deposition in the nerves and neuropathic manifestation in these models. This review gives a recent update on the milestone, progress, and challenges in developing different models for ATTR amyloidosis research.

No abstract

The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.