Obesity and diabetes are escalating worldwide health concerns, prompting the use of non-caloric sweeteners such as aspartame and stevia as substitutes for sucrose; however, their long-term physiologic Show more
Obesity and diabetes are escalating worldwide health concerns, prompting the use of non-caloric sweeteners such as aspartame and stevia as substitutes for sucrose; however, their long-term physiological and behavioral consequences remain incompletely understood. This work presents a comparative experimental study examining the long-term effects of sucrose, aspartame, and stevia intake on liver, heart, and brain functions in rats, while exploring the capacity of astaxanthin (ASTX) to attenuate the resulting tissue impairments. Seven rat groups-including control, sucrose, aspartame, stevia, and each sweetener combined with ASTX-were treated for 8 weeks to compare the organ-specific toxicity of the sweeteners and assess the protective effects of ASTX. Comprehensive evaluations of liver, heart, and brain were conducted using biochemical, behavioral, and histopathological analyses. All three sweeteners induced hyperglycemia, disrupted lipid metabolism (triglycerides, LDL, HDL), and increased oxidative stress (MDA), suppressing Nrf2/HO-1 antioxidant pathway and activating TLR4/NF-κB-mediated inflammation, leading to apoptosis. Biomarkers revealed liver dysfunction (ALT, AST, ALP), cardiac injury (troponin I, CK-MB, MEF2), and cognitive impairment (amyloid-beta, tau, BDNF), alongside altered monoamine neurotransmitters and Wnt3a/GSK-3β/β-catenin dysregulation. Bax/Bcl-2 ratio indicated enhanced apoptosis, with aspartame exerting the highest toxicity and stevia the least. While ASTX effectively alleviated these biochemical, histological, and functional changes. These findings suggest that aspartame has the strongest negative impact on liver, heart, and brain health, while stevia has the least, and that ASTX may serve as a potential protective agent against these harmful impacts. Show less
Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identifie Show more
Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management. Show less