Background: The Western-style diet-induced type 2 diabetes mellitus (T2D) may eventually trigger neurodegeneration and memory impairment. Thus, it is essential to identify effective therapeutic strategies to overcome T2D complications. This study aimed to investigate the effects of environmental enrichment (EE) and metformin interventions on metabolic dysfunctions, hippocampal neuronal death, and hippocampal-dependent memory impairments in high-fat/high-sucrose (HFS) diet-induced T2D rats. Methods: Thirty-two male rats (200–250 g) were divided into four groups: C group (standard diet + conventional cage); D group (HFS diet + conventional cage); DE group (HFS diet + EE cage/6hr daily); and DM group (HFS diet + metformin + conventional cage). Body weight was measured every week. T-maze tasks, anthropometric, biochemical, histological, and morphometric parameters were measured. The expression changes of hippocampal genes were also analyzed. Results: The anthropometric and biochemical parameters were improved in DE and DM groups compared with the D group. DE and DM groups had significantly higher T-maze percentages than the D group. These groups also had better histological and morphometric parameters than the D group. The interventions of EE and metformin enhanced the expression of hippocampal genes related to neurogenesis and synaptic plasticity (BDNF/TrkB binding, PI3K-Akt, Ras–MAPK, PLCγ–Ca²⁺, and LTP). Conclusion: Environmental enrichment (EE) and metformin improved metabolic functions, hippocampal neuron survival, and hippocampal-dependent memory in HFS diet-induced T2D rats. The underlying mechanisms of these interventions involved the expression of genes that regulate neurogenesis and synaptic plasticity.

Warthin-Starry (WS) staining is an ancillary stain used in the detection of Helicobacter sp., spirochaete and other microorganisms in tissue sections. The present study aimed to determine the validity of WS stain in the confirmation of H. pylori diagnosis in gastric biopsies in comparison with anti-H. pylori immunohistochemistry (IHC) staining. This study involved 104 cases of gastric biopsies that were previously subjected to WS staining. All cases involved retrieval of formalin-fixed paraffin-embedded (FFPE) gastric biopsies that were re-cut, subjected to anti-H. pylori IHC staining and reviewed blindly by a pathologist. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WS as compared to IHC were calculated. In this study, WS stain was less sensitive in detecting H. pylori. The sensitivity, specificity, PPV and NPV for WS stain were 50.0%, 92.4%, 79.2% and 76.3%, respectively. The sensitivity of WS stain in the histopathology laboratory was lower than that described previously. Several external factors that might influence the results were identified. However, sufficient information on patients' history of treatment and medication would be required for the diagnosis or confirmation of the presence of H. pylori in gastric biopsies by WS staining.