👤 Parmis Mansouri

Antioxidant supplements have emerged as promising strategies to mitigate the impact of Alzheimer's disease (AD) and associated dementia. We explored the neuroprotective potential of Carvone nanoemulsion (CANO) using a rat model of AD-associated dementia. Our experimental groups comprised non-AD control rats (CON), untreated AD rats (AD), and AD rats treated with CANO at two different dosages: 40 mg/kg (CANO40) and 80 mg/kg (CANO80). We assessed various behavioral parameters, malondialdehyde (MDA) and brain-derived neurotrophic factor (BDNF) levels,ferric-reducing ability of plasma (FRAP). AD induction caused a significant reduction in step-through latency (P < 0.001), center time (P < 0.001), the number of visits (P < 0.001), and total distance traveled (P < 0.001), time spent in open arms (P < 0.001), and both FRAP (P < 0.001) and BDNF levels (P < 0.001) in comparison to the CON group, while elevating escape latency, time in target zone and platform location latency, and MDA levels (P < 0.001). Treatment with CANO, particularly at the CANO80 dosage, significantly improved these parameters compared to the AD group, resulting in decreased time in the target zone (P < 0.001), escape latency (P < 0.001), and platform location latency (P < 0.001) and higher FRAP (P < 0.05) and BDNF levels (P < 0.05), along with decreased MDA levels (P < 0.05). CANO, especially at the 80 mg/kg dosage, shows promise in alleviating symptoms associated with AD-associated dementia. However, further research is warranted to validate and expand upon these findings. Show less

Coronary microvascular dysfunction (CMD) is increasingly recognized as a major driver of myocardial ischemia, with important implications for cardiovascular prognosis and quality of life, particularly in populations with ischemia and non-obstructive coronary arteries (INOCA) and heart failure with preserved ejection fraction (HFpEF). Despite increasing recognition of its importance, the mechanisms underlying CMD remain incompletely defined, and disease-modifying therapies are lacking. Lipoprotein(a) [Lp(a)], a genetically determined and causal cardiovascular risk factor, has been extensively studied in epicardial coronary atherosclerosis; however, its role in the coronary microcirculation has received comparatively limited attention. Lp(a) exhibits unique structural and biological properties, including the antifibrinolytic effects of apolipoprotein(a) and carriage of oxidized phospholipids, which promote endothelial dysfunction, oxidative stress, inflammatory activation, microvascular remodeling, and microthrombotic susceptibility-key processes implicated in CMD pathophysiology. Observational studies link elevated Lp(a) levels to impaired coronary flow reserve and endothelial dysfunction in patients with microvascular angina and related syndromes. Imaging and interventional studies further suggest that reduction of Lp(a)-associated circulating factors can improve myocardial perfusion and perfusion reserve in clinical settings dominated by microvascular disease. This review synthesizes current mechanistic, translational, and clinical evidence linking Lp(a) to CMD, identifies key knowledge gaps, and highlights future research priorities. Show less

Obicetrapib is a novel cholesteryl ester transfer protein (CETP) inhibitor with promising lipid-lowering effects. While earlier CETP inhibitors have shown inconsistent cardiovascular outcomes and safety concerns, the efficacy and safety of obicetrapib remain under active investigation. We systematically searched PubMed, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing obicetrapib versus placebo in adults with dyslipidemia or at high cardiovascular risk. We pooled mean differences (MDs) with 95 % confidence intervals (CI) with a random effects model. We used R software version 4.4.2 for statistical analysis. We included 7 RCTs comprising 3381 participants, of whom 2151 (63 %) received obicetrapib. The mean age was 64.3 years, and 36 % were women. Compared with placebo, obicetrapib significantly reduced mean LDL-C (MD: -37.21 %; 95 % CI: -41.53 to -32.90; Among patients with dyslipidemia and/or high cardiovascular risk, obicetrapib significantly reduces LDL-C, lipoprotein(a), apolipoprotein B, and non-HDL-C. No significant differences were observed in adverse events, supporting the favorable safety profile of obicetrapib. Show less

X-linked mutations are highly important in clinical diagnosis, and at least 533 disorders are related to the genes located on the X chromosome. A 21-year-old Caucasian woman with a 24-year-old Caucasian man as her fiancé referred Clinical genetic lab for premarital genetic counseling (carrier screening). None of them had any abnormal manifestations. Following genetic counseling, Whole Exome Sequencing (WES) test performed to find the possible pathogenic mutations. Also, after drawing the couple's pedigree, candidate mutations were examined in the woman's parents as well as her uncles. Additionally, Conclusively, the current study emphasizes the non-pathogenic effect of missense mutation R1362Q in the 35th exon of CACNA1F in association with ocular diseases. This will ensure the reports of this mutation as healthy instead of uncertain in the literature and databanks. Show less

Aluminum (Al) is known to induce neurotoxic effects, potentially contributing to Alzheimer's disease (AD) pathogenesis. Recent studies suggest that epigenetic modification may contribute to Al neurotoxicity, although the mechanisms are still debatable. Therefore, the objective of the present study was to summarize existing data on the involvement of epigenetic mechanisms in Al-induced neurotoxicity, especially AD-type pathology. Existing data demonstrate that Al exposure induces disruption in DNA methylation, histone modifications, and non-coding RNA expression in brains. Alterations in DNA methylation following Al exposure were shown to be mediated by changes in expression and activity of DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs). Al exposure was shown to reduce histone acetylation by up-regulating expression of histone deacetylases (HDACs) and impair histone methylation, ultimately contributing to down-regulation of brain-derived neurotrophic factor (BDNF) expression and activation of nuclear factor κB (NF-κB) signaling. Neurotoxic effects of Al exposure were also associated with aberrant expression of non-coding RNAs, especially microRNAs (miR). Al-induced patterns of miR expression were involved in development of AD-type pathology by increasing amyloid β (Aβ) production through up-regulation of Aβ precursor protein (APP) and β secretase (BACE1) expression (down-regulation of miR-29a/b, miR-101, miR-124, and Let-7c expression), increasing in neuroinflammation through NF-κB signaling (up-regulation of miR-9, miR-125b, miR-128, and 146a), as well as modulating other signaling pathways. Furthermore, reduced global DNA methylation, altered histone modification, and aberrant miRNA expression were associated with cognitive decline in Al-exposed subjects. However, further studies are required to evaluate the contribution of epigenetic mechanisms to Al-induced neurotoxicity and/or AD development. Show less

This study aimed to introduce a biomarker panel to detect pancreatic ductal adenocarcinoma (PDAC) in the early stage, and also differentiate of stages from each other. PDAC is a lethal cancer with poor prognosis and overall survival. Gene expression profiles of PDAC patients were extracted from the Gene Expression Omnibus (GEO) database. The genes that were significantly differentially expressed (DEGs) for Stages I, II, and III in comparison to the healthy controls were identified. The determined DEGs were assessed via protein-protein interaction (PPI) network analysis, and the hub-bottleneck nodes of analyzed networks were introduced. A number of 140, 874, and 1519 significant DEGs were evaluated via PPI network analysis. A biomarker panel including ALB, CTNNB1, COL1A1, POSTN, LUM, and ANXA2 is presented as a biomarker panel to detect PDAC in the early stage. Two biomarker panels are suggested to recognize other stages of illness. It can be concluded that ALB, CTNNB1, COL1A1, POSTN, LUM, and ANXA2 and also FN1, HSP90AA1, LOX, ANXA5, SERPINE1, and WWP2 beside GAPDH, AKT1, EGF, CASP3 are suitable sets of gene to separate stages of PDAC. Show less

Dyslipidemia is one of the major complications in patients with type 2 diabetes mellitus (T2DM). Dietary fat intake and genetic factors including CETP Taq1B polymorphism could also affect lipid profile concentrations, in particular HDL-c. We decided to study the frequency of this polymorphism and its interaction with dietary fat intake on HDL-c concentration among Iranian T2DM patients with and without dyslipidemia. In this comparative study, serum samples were collected from 55 patients with dyslipidemia and 129 patients without dyslipidemia. Validated semi-quantitative FFQ was used for food consumption data. CETP Taq1B polymorphism was studied by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). We used χ The frequency of B1B1 genotype was higher in patients with dyslipidemia (p = 0.01). There was no significant relationship between CETP Taq1B polymorphism and lipid profile concentrations. In patients without dyslipidemia, the interaction between the polymorphism and total fat intake on HDL-c concentration as well as TG/HDL ratio was significant (p = 0.02 and p = 0.009 respectively). This was more evident in B1B1 genotype. Moreover, HDL-c concentration was significantly higher in B2B2 genotype with low total fat intake. Higher total fat intake may affect the relationship between CETP Taq1B polymorphism and HDL-c concentration in patients with normolipidemic T2DM. Show less

The type 2 diabetes is one of the most common autoimmune diseases. Due to a key role in the metabolism of unsaturated fatty acids such as arachidonic acid, one of the most important precursors of immunity mediators, fatty acid desaturase (FADS) genes could have an important impact in the development of type 2 diabetes. This study aimed to determine the relationship between polymorphisms rs174537 in FADS1 gene and rs174575 in FADS2 gene with type 2 diabetes in Iranian population. After extracting genomic DNA, the locations of mutations and allele types were identified with high-resolution melting (HRM)-polymerase chain reaction method. Then, association between these mutations with metabolic syndrome, dyslipidemia, and type 2 diabetes was investigated using χ The results showed that among 50 diabetic participants, 68% of patients have the mutant allele for rs174537 in FADS1 gene. This rate is 26% for rs174575 in FADS2 gene. Based on the results, it seems that participants having rs174537 mutant allele are more prone to become diabetic but it has a beneficial effect on total and low-density lipoprotein cholesterol and participants having rs174575 mutant are less prone to become diabetic, and also, it leads to higher triglycerides and body mass index (obesity). Detecting FADS1 and FADS2, gene polymorphisms using HRM can be an anticipating tool for making decision on initiating lifestyle modifications to prevent type 2 diabetes. Show less

The central nervous system (CNS) constantly monitors nutrient availability in the body and, in particular, in the gastrointestinal (GI) tract to regulate nutrient and energy homeostasis. Extrinsic parasympathetic and sympathetic nerves are crucial for CNS nutrient sensing in the GI tract. These extrinsic afferent nerves detect the nature and amount of nutrients present in the GI tract and relay the information to the brain, which controls energy intake and expenditure accordingly. Dietary fat and fatty acids are sensed through various direct and indirect mechanisms. These sensing processes involve the binding of fatty acids to specific G protein-coupled receptors expressed either on the afferent nerve fibres or on the surface of enteroendocrine cells that release gut peptides, which themselves can modulate afferent nerve activity through their cognate receptors or have endocrine effects directly on the brain. Further dietary fat sensing mechanisms that are related to enterocyte fat handling and metabolism involve the release of several possible chemical mediators such as fatty acid ethanolamides or apolipoprotein A-IV. We here present evidence for yet another mechanism that may be based on ketone bodies resulting from enterocyte oxidation of dietary fat-derived fatty acids. The presently available evidence suggests that sympathetic rather than vagal afferents are involved, but further experiments are necessary to critically examine this concept. Show less

Hypertriglyceridemia is an independent risk factor for coronary artery disease. Because apolipoprotein (Apo)A5 regulates plasma triglyceride levels, we investigated the impact of human (h)ApoA5 on atherogenesis. The influence of hApoA5 transgenic expression was studied in the ApoE2 knock-in mouse model of mixed dyslipidemia. Our results demonstrate that hApoA5 lowers plasma triglyceride levels in Western diet-fed ApoE2 knock-in mice. Moreover, atherosclerotic lesion development was significantly decreased in the hApoA5 transgenic mice. Finally, pharmacologic activation of hApoA5 expression by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate resulted in an enhanced atheroprotection. These results identify an atheroprotective role of hApoA5 in a mouse model of mixed dyslipidemia. Show less