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Schinus molle L. (Anacardiaceae) has been traditionally used for conditions related to the nervous system and emotional well-being, often through aromatic preparations. However, its cognition-specific effects have not yet been investigated. To assess the cognitive effects of the fruit-derived essential oil of Schinus molle L. (SMEO), administered via oral and inhalation routes, in a rat model of scopolamine-induced amnesia. SMEO was obtained by hydrodistillation and characterised by GC-MS/GC-FID. Amnesic rats received SMEO for 14 days by inhalation (1% or 3%) or oral gavage (100 or 200 mg/kg). Cognition was assessed by Morris water maze (MWM), passive avoidance (PA), and novel object recognition (NOR) tests; locomotion was measured by activity-meter. Hippocampal BDNF and GFAP immunoreactivity were assessed by immunohistochemistry. SMEO was dominated by α-phellandrene (48.7%). Scopolamine impaired cognition, whereas SMEO attenuated deficits with efficacy comparable to piracetam. Key behavioural and immunohistochemical findings (main omnibus statistical effects) were as follows: In the MWM, treatment and time effects on escape latency were significant (both p < 0.001), and probe performance improved (p < 0.001). PA retention was restored (p < 0.001) and the NOR index improved (p < 0.001), without locomotor changes (all p > 0.05). Scopolamine reduced hippocampal BDNF immunoreactivity in CA1 and DG (p < 0.01) and CA3 (p < 0.001), which was restored by SMEO via both routes. GFAP immunoreactivity was reduced in CA1/CA3/DG (all p < 0.001) and was rescued selectively after inhalation. These findings provide preclinical evidence consistent with an ethnopharmacological rationale for SMEO and support further translational work to clarify its relevance beyond this experimental paradigm. Show less

β-Amyloid (Aβ) is generated from the amyloid precursor protein (APP) through sequential cleavage by β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase, where BACE1 acting as the rate-limiting enzyme. Elevated BACE1 levels in the brains of Alzheimer's disease (AD) patients implicate that dysregulated BACE1 expression is crucial to AD pathogenesis. However, the underlying regulatory mechanisms remain unclear. Here, we identified that the G protein subunit β5 gene (Gnb5), a component of the G protein-coupled receptor (GPCR) signaling pathway, is significantly downregulated in both human AD patients and AD mouse models. Conditional knockout of Gnb5 in excitatory neurons resulted in cognitive impairments, whereas adeno-associated virus (AAV)-mediated overexpression of Gnb5 in the hippocampus ameliorated cognitive deficits and reduced Aβ deposition in 5xFAD mice. Mechanistically, we demonstrated that Gnb5 interacts with BACE1, modulating its expression and potentially influencing Aβ generation. We further identify the first tryptophan-aspartate domain (WD domain) of Gnb5 and the Ser81 residue as crucial for this regulation. Expression of this WD domain alone is sufficient to reduce Aβ deposition in 5xFAD mice, whereas a point mutation at Ser81 (S81L) abolishes this effect. Overall, our findings establish Gnb5 as a negative regulator of the BACE1-APP processing axis and unveil mechanistic insights into its role in Aβ-mediated AD pathogenesis. Show less

Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits. Show less

Chickpea is a legume that grows in most parts of the world. It is negatively affected by abiotic and biotic factors like drought and fungal diseases, respectively. One of the most important soil-borne pathogens affecting chickpeas is Show less

The aim of this study was to examine the relationship between APOA4 gene T347S polymorphism with obesity measures and serum lipids in Turkish adults. Randomly selected sample of 1,554 adults (754 men, mean age 50.4 ± 11.9 years and 800 women, mean age 49.6 ± 11.8 years) were included in the study. 346 Women (43.2 %) were postmenopausal. Genotyping was performed by using hybridization probes in real-time PCR. Not men but postmenopausal women, carrying the S347 allele, were associated with 1.5 kg/m(2) higher BMI (P = 0.016) and 3.6 cm wider waist circumference (P = 0.005) than postmenopausal T347 homozygotes, controlled for covariates. Logistic regression analyses of this polymorphism, adjusted for age, fasting triglyceride, smoking status, alcohol consumption and physical activity disclosed the rare allele to be associated with obesity in postmenopausal women at an odds of 1.80 (95 % CI 1.09-2.97; P = 0.021). Serum apoB level was lower in S347 allele carriers (110.9 ± 2.9 mg/dL) than in T347 homozygotes (119.0 ± 2.4 mg/dL; P = 0.035) in men but not women. APOA4 T347S polymorphism was unrelated to lipids and other lipoproteins in either gender. The APOA4 S347 allele predisposes to obesity and high waist circumference in Turkish postmenopausal women. ApoB levels are lower only in men in S347 allele carriers. Show less

Apolipoprotein C3 (APOC3) gene polymorphisms are associated with cardiometabolic risk factors, varying in ethnicities. This study aimed to investigate such association between the APOC3 -482C>T polymorphism and cardiometabolic risk factors in the turkish adult risk factor (TARF) study cohort, stratifying by gender and obesity. Randomly selected 1548 individuals (757 male and 791 female, mean age 49.9±11.8 years) were genotyped for -482C>T polymorphism using hybridization probes in a Real-Time PCR LC480 device. The -482TT genotype prevailed 9.9% in men and 11.5% in women. Association between 482C>T polymorphism and dyslipidemia (p=0.036, OR=1.42, 95%Cl=1.02-1.97) was found only in men. Analysis of variance showed that anthropometric and metabolic variables were not differently distributed in APOC3 -482C>T genotypes in the study population. In relation to dyslipidemia and obesity, the -482C>T polymorphism showed significant gender-by-genotype interactions (p<0.01). When the study population was stratified according to gender and obesity, homozygotes for the T allele were associated strongly with (by 45%) elevated fasting triglyceride concentrations in obese men (p=0.009) and homeostatic model assessment (HOMA) index in non-obese women (p=0.013). Furthermore, in the same subgroups, the associations of the fasting triglyceride concentrations and HOMA index with the TT genotype remained after adjustment for risk factors (p<0.05). APOC3 -482TT genotype is independently associated with elevated fasting triglyceride concentrations in obese men. Presence of obesity seems to be required for this genotype to induce markedly elevated triglycerides. Furthermore, it is associated with the dyslipidemia in men, without requirement of obesity. Show less

Apolipoprotein A5 (APOA5) gene polymorphisms are usually associated with plasma triglyceride levels. We evaluated the relationship of the APOA5 -1131T>C and c.56C>G polymorphisms [single nucleotide polymorphism (SNP)] with serum lipids, dyslipidemia [low high-density lipoprotein (HDL)/high triglyceride] and the risk for metabolic syndrome (MS) in the Turkish Adult Risk Factor study. We genotyped SNPs using the Taqman allelic discrimination assays in 1564 Turkish adults (51.4% female, mean age 54.1+/-11.6 years). MS and dyslipidemia were defined using the criteria of the National Cholesterol Education Program. For both SNPs, rare allele carriers had significantly higher fasting triglyceride levels in both genders, except the c.56G allele in men. The -1131C allele was associated with lower HDL cholesterol (HDL-C) levels in women. In relation to dyslipidemia, the c.56C>G and haplotype 1 had significant gender-genotype interactions (p<0.05). Otherwise, both SNPs were significantly associated with dyslipidemia after adjustment for risk factors in women. After similar adjustment, non-carriers of the haplotype 1 (odds ratio=4.1, p=0.003) increased the MS risk in women. However, no significant associations emerged between SNPs and HDL-C, dyslipidemia or MS in a similar analysis in men. Excess risk for low HDL-C, dyslipidemia and MS is associated with the rare alleles of the APOA5 SNPs and non-carriers of common haplotype in women. Show less