Donepezil Protects Against Doxorubicin-Induced Chemobrain in Rats via Attenuation of Inflammation and Oxidative Stress Without Interfering With Doxorubicin Efficacy

Although doxorubicin (Dox) is an effective chemotherapy medication used extensively in the treatment of breast cancer, it frequently causes debilitating neurological deficits known as chemobrain. Donepezil (DPZ), an acetylcholinesterase inhibitor, provides therapeutic benefits in various neuropathological conditions. However, comprehensive mechanistic insights regarding the neuroprotection of DPZ on cognition and brain pathologies in a Dox-induced chemobrain model remain obscure. Here, we demonstrated that Dox-treated rats manifested conspicuous cognitive deficits and developed chemobrain pathologies as indicated by brain inflammatory and oxidative insults, glial activation, defective mitochondrial homeostasis, increased potential lesions associated with Alzheimer’s disease, disrupted neurogenesis, loss of dendritic spines, and ultimately neuronal death through both apoptosis and necroptosis. Intervention with DPZ co-treatment completely restored cognitive function by attenuating these pathological conditions induced by DOX. We also confirmed that DPZ treatment does not affect the anti-cancer efficacy of Dox in breast cancer cells. Together, our findings suggest that DPZ treatment confers potential neuroprotection against Dox-induced chemobrain.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01092-9.     

Effect of Swiss-type heterocellular HPFH from XmnI-Gγ and HBBP1 polymorphisms on HbF,HbE, MCV and MCH levels in Thai HbE carriers

Relationships of Swiss-type heterocellular HPFH as functions of XmnI-^Gγ and HBBP1:rs2071348 polymorphisms and HbF, HbE, MCV and MCH in HbE carriers were evaluated in 52 non-anemic and α-thalassemia-free Thai HbE carriers. HbF and HbE levels were measured using cation-exchange HPLC. MCV and MCH were determined using an automated blood counter. The XmnI-^Gγ polymorphism was identified by XmnI digestion of amplified products, and the HBBP1:rs2071348 polymorphism by tetra-ARMS-PCR. HbF levels in HbE carriers were higher than those in normal individuals. HbF levels >0.8 % indicated the Swiss-type heterocellular HPFH in these subjects, rendering a prevalence of 40.4 %. The XmnI-^Gγ (+) and HBBP1:rs2071348 (C) alleles were modestly positively correlated with elevated HbF, elevated MCH and lowered HbE values. This study thus confirms the influence of the XmnI-^Gγ and HBBP1:rs2071348 polymorphisms on HbF production. The present study demonstrates the association of XmnI-^Gγ and HBBP1:rs2071348 with HbF, HbE, MCV and MCH in HbE carriers for the first time, and highlights the effect of elevated HbF production on HbE levels.     

Chronic treatment with prebiotics,probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats

European Journal of Nutrition - In metabolic syndrome, the composition of gut microbiota has been disrupted, and is associated with left ventricular (LV) dysfunction. Several types of prebiotics,...     

A modified sandwich ELISA for accurate measurement of HbF in α-thalassemia carriers containing Hb Bart’s and Hb Portland 1

Hemoglobin F (HbF) in blood lysate can be accurately measured by various methods, including immunoassay. In this study, we have produced polyclonal antibody (pAb) against HbF and established a modified sandwich-type ELISA for HbF quantification in blood lysates. The modified sandwich ELISA utilized anti-γ-globin monoclonal antibody clones Thal N/B as the capture antibody (Ab) coated on solid-phase, fluorescein isothiocyanate (FITC)-labeled pAb as the detecting Ab, and HPR-labeled anti-FITC Ab as the signal-generating Ab. By using an optimized blood lysate dilution, the HbF could be measured with no interference from hemoglobin Bart’s (Hb Bart’s) and hemoglobin Portland (Hb Portland 1) presented in α-thalassemia carriers. HbF levels measured by the modified sandwich ELISA were comparable to those quantified by the standard cation-exchange high performance liquid chromatography. We suggested that this modified sandwich ELISA was able to accurately measure HbF levels even in α-thalassemia carriers containing Hb Bart’s and Hb Portland 1 and be an alternative method for HbF measurement.     

Modulating mitochondrial dynamics attenuates cardiac ischemia-reperfusion injury in prediabetic rats

Mitochondria are extraordinarily dynamic organelles that have a variety of morphologies,the status of which are controlled by the opposing processes of fission ...