Exploring the Therapeutic Potential of Benfotiamine in a Sporadic Alzheimer's-Like Disease Rat Model: Insights into Insulin Signaling and Cognitive function.

Alzheimer's disease (AD) is a complex neurodegenerative process, also considered a metabolic condition due to alterations in glucose metabolism and insulin signaling pathways in the brain, which share similarities with diabetes. This study aimed to investigate the therapeutic effects of benfotiamine (BFT), a vitamin B1 analog, in the early stages of the neurodegenerative process in a sporadic model of Alzheimer's-like disease induced by intracerebroventricular injection of streptozotocin (STZ). Supplementation with 150 mg/kg of BFT for 7 days reversed the cognitive impairment in short- and long-term memories caused by STZ in rodents. We attribute these effects to BFT's ability to modulate glucose transporters type 1 and 3 (GLUT1 and GLUT3) in the hippocampus, inhibit GSK3 activity in the hippocampus, and modulate the insulin signaling in the hippocampus and entorhinal cortex, as well as reduce the activation of apoptotic pathways (BAX) in the hippocampus. Therefore, BFT emerges as a promising and accessible intervention in the initial treatment of conditions similar to AD.

The bank robbery analogy as a first approach for understanding basic concepts of synthesis, transport, and mechanism of action of hormones.

Learning endocrine physiology can be challenging. Some physiological concepts are abstract, making the process of learning more difficult for students. The comprehension of basic concepts, such as chemical hormone classification, is essential to understand the differences in synthesis, secretion, transport, and mechanism of action of hormones. To assist the students on this subject, we developed an analogy between the basic concepts of hormone synthesis, transport, and mechanism of action and a bank robbery as a first approach to engage and stimulate their learning process. In the analogy, the students are asked to help identify and characterize two bank robbery crews based on a set of evidence collected by the police. The goal is to identify the general profile of lipid- and water-soluble hormones synthesis, transport, and mechanism of action on target cells. When applying the activity, the students showed a great deal of interest in solving the crime and they seemed to understand the similarities between the analogy and the subject.NEW & NOTEWORTHY Two endocrine bank robbery crews are being searched by the police. As an endocrine system student, you have been summoned to help the police solve the robberies.

Characterization of the binding interaction between atrazine and human serum albumin: Fluorescence spectroscopy, molecular dynamics and quantum biochemistry.

Atrazine (ATR), one of the most used herbicides worldwide, causes persistent contamination of water and soil due to its high resistance to degradation. ATR is associated with low fertility and increased risk of prostate cancer in humans, as well as birth defects, low birth weight and premature delivery. Describing ATR binding to human serum albumin (HSA) is clinically relevant to future studies about pharmacokinetics, pharmacodynamics and toxicity of ATR, as albumin is the most abundant carrier protein in plasma and binds important small biological molecules. In this work we characterize, for the first time, the binding of ATR to HSA by using fluorescence spectroscopy and performing simulations using molecular docking, classical molecular dynamics and quantum biochemistry based on density functional theory (DFT). We determine the most likely binding sites of ATR to HSA, highlighting the fatty acid binding site FA8 (located between subdomains IA-IB-IIA and IIB-IIIA-IIIB) as the most important one, and evaluate each nearby amino acid residue contribution to the binding interactions explaining the fluorescence quenching due to ATR complexation with HSA. The stabilization of the ATR/FA8 complex was also aided by the interaction between the atrazine ring and SER454 (hydrogen bond) and LEU481(alkyl interaction).

Use of Hormone Therapy in Postmenopausal Women with Alzheimer's Disease: A Systematic Review.

BACKGROUND: Around two-thirds of patients with Alzheimer's disease (AD) are women, which could be related to the depletion of female sexual hormones at menopause. The replacement of these hormones with hormone therapy (HT) to possibly decrease AD risk or treat AD patients has generated conflicting results in the literature. OBJECTIVE: Our aim was to systematically review the relationship between HT use in postmenopausal women with AD and the risk of developing or treating AD symptoms. DATA SOURCES: The PubMed, LILACS, Scopus, Scielo, and Web of Science databases were searched from January 1994 to December 2020 using the descriptors 'Alzheimer Disease OR Alzheimer's Disease' and 'Hormone Replacement Therapy OR Estrogen Replacement Therapy'. STUDY SELECTION: Observational and controlled clinical trials including postmenopausal women diagnosed with AD and evaluating HT efficacy were eligible for inclusion. DATA EXTRACTION: Extracted data comprise study design, covariates, inclusion criteria for sample selection, AD diagnosis criteria, biases, HT regimen, and cognitive measurement tools used. RESULTS: Overall, 25 studies were selected. Among the 14 observational studies, 8 reported an improvement in cognitive function and a decrease in AD risk, especially in younger postmenopausal women. Five observational studies did not demonstrate any association between HT and AD, and one study reported an increase in AD risk, regardless of time of HT initiation. Of the 11 controlled clinical trials included, 7 showed an amelioration in cognitive function after HT. The remaining 4 trials saw no difference between HT and control. CONCLUSION: Both observational and controlled clinical trials had methodological issues and discrepancies in inclusion criteria and HT protocols. These inconsistencies made it difficult to establish an association between HT and AD.

Molecular insight on the binding of stevia glycosides to bovine serum albumin.

The interaction of the steviol and its glycosides (SG), steviolbioside, and rebaudioside A, with bovine serum albumin (BSA) was studied by absorption and fluorescence spectroscopy techniques alongside molecular docking. The stevia derivatives quenched the fluorescence of BSA by a dynamic quenching mechanism, indicating the interaction between the stevia derivatives and BSA. The binding constant (Kb) of steviol was 100-1000-fold higher than those of SG. The stevia derivative/BSA binding reaction was spontaneous and involved the formation of hydrogen bonds and van der Waals interactions between steviol and steviolbioside with BSA, and water reorganization around the rebaudioside A/BSA complex. Molecular docking pointed out the FA1 and FA9 binding sites of BSA as the probable binding sites of steviol and SG, respectively. In conclusion, steviol enhanced hydrophobicity and small size compared to SG may favor its binding to BSA. As steviol and its glycosides share binding sites on BSA with free fatty acids and drugs, they may be competitively displaced from plasma albumin under various physiological states or disease conditions. These findings are clinically relevant and provide an insight into the pharmacokinetics and pharmacodynamics of the stevia glycosides.

Is hypovitaminosis D associated with fibromyalgia? A systematic review.

CONTEXT: Recent findings have suggested a high prevalence of vitamin D deficiency or insufficiency in fibromyalgia (FM) patients despite the lack of clinical and pathophysiological evidence. OBJECTIVE: A systematic review was conducted to examine the association between vitamin D status and FM, including the effect of vitamin D supplementation. DATA SOURCE: PubMed, LILACS, Scopus, SciELO, Cochrane, and EMBASE were searched, from January 2000 to July 2018, using the descriptors "Fibromyalgia" and "Vitamin D." STUDY SELECTION: Trials including FM patients in whom vitamin D levels were assessed were eligible for inclusion. DATA EXTRACTION: Data comprised age, gender, country, aims, bias, diagnosis criteria, cutoff point, and status of vitamin D, together with FM symptoms and vitamin D supplementation protocol. RESULTS: A total of 26 articles were selected. Most of the studies were found to present unreliable control groups and small samples. Experimental data on vitamin D supplementation indicated improvement in certain FM symptoms. CONCLUSION: Prevalence of hypovitaminosis D in the FM population and the cause-effect relationship were inconclusive. Nevertheless, vitamin D supplementation may be considered as a co-adjuvant in FM therapy.