Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. RESULTS: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. DISCUSSION: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. HIGHLIGHTS: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

APOE genotype, eicosapentaenoic acid (EPA) supplementation and n-3 highly unsaturated fatty acid (HUFA) levels in patients with multiple colorectal polyps: A secondary analysis of the seAFOod polyp prevention trial.

INTRODUCTION: We examined the relationship between Apolipoprotein E (APOE) genotype and n-3 highly unsaturated fatty acid (HUFA) levels in participants of the seAFOod trial, who were undergoing colonoscopy surveillance after removal of colorectal polyps. METHODS: Baseline and on-treatment (eicosapentaenoic acid [EPA] 2 g daily or placebo for 6 months) levels of n-3 HUFAs, and plasma 18-hydroxyeicosapentaenoic acid (HEPE), were analysed according to APOE genotype (based on polymorphisms rs429358 and rs7412) in 584 participants. RESULTS: Before treatment, APOE2/2 individuals had lower levels, and APOE4/4 participants had higher levels, of n-3 HUFAs, including EPA, than APOE3/3 counterparts (P < 0.01 for the APOE2/2 versus APOE4/4 comparison). After EPA supplementation, n-3 HUFA levels were not significantly different when stratified by APOE genotype, although APOE4 carriers displayed lower plasma 18-HEPE levels than individuals without an APOE4 allele (P = 0.002). CONCLUSIONS: APOE genotype is associated with differential n-3 HUFA and 18-HEPE levels in individuals with multiple colorectal polyps.

The incorporation of sumac seed powder (Rhus coriaria L.) into the diet of quail breeders as a novel feed additive.

A total of 150 adult quails, aged 8 wk, were divided into 5 groups to study the effect of sumac seed powder on reproductive and productive parameters, egg quality, digestive enzymes, and quail breeders' blood profiles. Dietary supplements containing sumac powder were formulated as follows: group 1 (G1) (control, only basal diet); group 2 (G2) (basal diet + 1 g sumac powder/kg diet); group 3 (G3) (basal diet + 2 g sumac powder/kg diet); group 4 (G4) (basal diet + 3 g sumac powder/kg diet); and group 5 (G5) (basal diet + 4 g sumac powder/kg diet). The feed conversion ratio was significantly higher at all levels of sumac powder (P < 0.05) compared to the control group (G1). Overall, during the study (8-16 wk), quail-fed 3 g sumac powder/kg diet (G4) showed no significant increase (P > 0.05) in the feed intake compared to the control group. Sumac powder supplementation significantly (P < 0.05) increased egg number, egg weight, egg mass, fertility, and hatchability. While supplementing with sumac powder did not impact other egg quality parameters, it did significantly (P < 0.05) increase yolk percentage, Haugh unit, and unit surface shell weight. Furthermore, when compared to the control group (G1), birds given 2, 3, or 4 g of sumac powder/kg diet showed a significant improvement (P < 0.05) in hematological parameters such as red blood cells, white blood cells, and hemoglobin, as well as a decrease in glucose levels. Feeding quail with a 3 g sumac powder/kg diet (G4) resulted in significantly (P < 0.05) higher globulin levels and improved albumin/globulin ratio compared to other treatments and control (G1). Sumac powder intake significantly (P < 0.05) reduced plasma lipid profile, liver enzymes (aspartate aminotransferase, and alanine aminotransferase), and kidney functions (creatinine, and urea). Furthermore, the supplementation of sumac powder resulted in a substantial increase (P < 0.05) in the levels of amylase, lipase, and protease. Sumac powder administration also significantly (P < 0.05) improves immunity by boosting IgM, IgG, IgA, and lysozyme levels in quail breeders' plasma. Supplementing with sumac powder, on the other hand, increased levels of reduced glutathione, total antioxidant capacity, catalase, and superoxide dismutase. The results of the current study indicated that the addition of 1, 2, 3, and 4 g of sumac powder to the diet of Japanese quail breeders led to improvements in egg quality, digestive enzymes, reproductive and productive performances, and most blood hematological and biochemical parameters.

Investigating the synergistic effects of hormone replacement therapy, apolipoprotein E and age on brain health in the UK Biobank.

Global prevalence of Alzheimer's Disease has a strong sex bias, with women representing approximately two-thirds of the patients. Yet, the role of sex-specific risk factors during midlife, including hormone replacement therapy (HRT) and their interaction with other major risk factors for Alzheimer's Disease, such as apolipoprotein E (APOE)-e4 genotype and age, on brain health remains unclear. We investigated the relationship between HRT (i.e., use, age of initiation and duration of use) and brain health (i.e., cognition and regional brain volumes). We then consider the multiplicative effects of HRT and APOE status (i.e., e2/e2, e2/e3, e3/e3, e3/e4 and e4/e4) via a two-way interaction and subsequently age of participants via a three-way interaction. Women from the UK Biobank with no self-reported neurological conditions were included (N = 207,595 women, mean age = 56.25 years, standard deviation = 8.01 years). Generalised linear regression models were computed to quantify the cross-sectional association between HRT and brain health, while controlling for APOE status, age, time since attending centre for completing brain health measure, surgical menopause status, smoking history, body mass index, education, physical activity, alcohol use, ethnicity, socioeconomic status, vascular/heart problems and diabetes diagnosed by doctor. Analyses of structural brain regions further controlled for scanner site. All brain volumes were normalised for head size. Two-way interactions between HRT and APOE status were modelled, in addition to three-way interactions including age. Results showed that women with the e4/e4 genotype who have used HRT had 1.82% lower hippocampal, 2.4% lower parahippocampal and 1.24% lower thalamus volumes than those with the e3/e3 genotype who had never used HRT. However, this interaction was not detected for measures of cognition. No clinically meaningful three-way interaction between APOE, HRT and age was detected when interpreted relative to the scales of the cognitive measures used and normative models of ageing for brain volumes in this sample. Differences in hippocampal volume between women with the e4/e4 genotype who have used HRT and those with the e3/e3 genotype who had never used HRT are equivalent to approximately 1-2 years of hippocampal atrophy observed in typical health ageing trajectories in midlife (i.e., 0.98%-1.41% per year). Effect sizes were consistent within APOE e4/e4 group post hoc sensitivity analyses, suggesting observed effects were not solely driven by APOE status and may, in part, be attributed to HRT use. Although, the design of this study means we cannot exclude the possibility that women who have used HRT may have a predisposition for poorer brain health.

Effects of varying dietary microalgae levels on performance, egg quality, fertility, and blood biochemical parameters of laying Japanese quails (Coturnix coturnix Japonica).

This experiment was carried out to investigate the nutritional value of Spirulina and Dunaliella (SD) combination levels (0, 0.5, 1.0, 1.5, and 2.0 g/kg) that affected the laying Japanese quail's efficiency, egg quality, fertility, and blood biological indicators. A total of 150 adult Japanese quails, aged 8 wk, were divided into 5 treatments at random, each consisting of 30 quails. There were 5 duplicates for every treatment, with 2 male and 4 female quails in each. Comparing the addition of various concentrations of a mixture of SD to the control treatment, the results showed no substantial rise in egg production, egg weight, or egg mass. When compared to the control group, final body weight (FBW) was improved with SD supplementation. The quails in control consumed more feed intake (FI) (p < 0.05), and they were different from the groups who got SD therapy in that they had a regular feed conversion ratio (FCR). The percentages of hatchability and fertility increased when SD was added to quail meals at up to 1.00 g/kg. When compared to the control quail, the quail supplemented with SD levels showed a non-significant rise in albumin%, yolk%, Haugh unit, and unit surface shell weight (USSW), as well as an increase in eggshell percentage and a drop in egg shape index (p < 0.05). Renal and hepatic enzyme functioning improved when SD was added to the diets. Additionally, lipid profile indicators were reduced by SD supplementation (except low-density lipoprotein-LDL). Moreover, compared to the control, incorporating SD led to a nonsignificant rise in immunoglobulin concentrations (IgG and IgM). In conclusion, adding SD to the diet can improve body weight, lipid profile, immunological response, and liver and kidney functions in Japanese quail.

Polymorphisms in Cyclooxygenase, Lipoxygenase, and TP53 Genes Predict Colorectal Polyp Risk Reduction by Aspirin in the seAFOod Polyp Prevention Trial.

Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35 SNPs in oxylipin metabolism genes such as cyclooxygenase (PTGS) and lipoxygenase (ALOX), as well as 7 SNPs already associated with colorectal cancer risk reduction by aspirin (e.g., TP53; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomized 2 × 2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the P and q value. 542 (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with nonaspirin users was restricted to rs4837960 (PTGS1) common homozygotes [IRR, 0.69; 95% confidence interval (CI), 0.53-0.90); q = 0.06], rs2745557 (PTGS2) compound heterozygote-rare homozygotes [IRR, 0.60 (0.41-0.88); q = 0.06], rs7090328 (ALOX5) rare homozygotes [IRR 0.27 (0.11-0.64); q = 0.05], rs2073438 (ALOX12) common homozygotes [IRR, 0.57 (0.41-0.80); q = 0.05], and rs104522 (TP53) rare homozygotes [IRR, 0.37 (0.17-0.79); q = 0.06]. No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalized, predictive models of colorectal cancer chemoprevention by aspirin. PREVENTION RELEVANCE: Single-nucleotide polymorphisms in genes controlling lipid mediator signaling may modify the colorectal polyp prevention activity of aspirin. Further investigation is required to determine whether testing for genetic variants can be used to target cancer chemoprevention by aspirin to those who will benefit most.

Walnut Kernel Oil and Defatted Extracts Enhance Mesenchymal Stem Cell Stemness and Delay Senescence.

Decreased stemness and increased cellular senescence impair the ability of mesenchymal stem cells (MSCs) to renew themselves, change into different cell types, and contribute to regenerative medicine. There is an urgent need to discover new compounds that can boost MSCs' stemness and delay senescence. Therefore, this study aimed to investigate the impact of walnut kernel oil (WKO) and defatted (WKD) extracts on bone marrow (BM)-MSC stemness and senescence. Premature senescence and inflammation were induced in BM-MSCs using H2O2 and LPS, respectively. Phytochemical constituents of WKO and WKD extracts were detected by HPLC. The stemness (proliferation and migration), senescence-related markers (p53, p21, SIRT1, and AMPK), oxidative stress/antioxidant markers, inflammatory cytokines, and cell cycle of BM-MSCs were measured by MTT assay, qPCR, ELISA, and flow cytometry. WKO and WKD extracts improved rat BM-MSC stemness, as evidenced by (1) increased cell viability, (2) decreased apoptosis (low levels of Bax and caspase3 and high levels of Bcl2), (3) upregulated MMP9 and downregulated TIMP1 expression, and (4) cell cycle arrest in the G0/G1 phase and declined cell number in the S and G2/M phases. Additionally, WKO and WKD extracts reduced rat BM-MSC senescence, as indicated by (1) decreased p53 and p21 expression, (2) upregulated expression and levels of SIRT1 and AMPK, (3) reduced levels of ROS and improved antioxidant activity (higher activity of CAT, SOD, and GPx and upregulated expression of NrF2 and HO-1), and (4) declined levels of TNFα, IL1ß, and NF-κB. When compared to the WKO extract, the WKD extract had a greater impact on the induction of stemness and reduction of senescence of BM-MSCs due to its stronger antioxidant activity, which could be attributed to its higher levels of flavonoids and phenolic compounds, as detected by HPLC analysis. WKO and WKD extracts enhance rat BM-MSC stemness and protect them from senescence, suggesting their potential use as enhancers to increase MSCs' therapeutic efficacy.

The Influence of APOE Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice.

The apolipoprotein E4 (APOE4) genotype is predictive of Alzheimer's disease (AD). The brain is highly enriched with the omega-3 polyunsaturated fatty acid (n3-PUFA), docosahexaenoic acid (DHA). DHA's metabolism is defective in APOE4 carriers. Flavanol intake can play a role in modulating DHA levels. However, the impact of flavanol co-supplementation with fish oil on brain DHA uptake, status and partitioning, and according to APOE genotype is currently unknown. Here, using a humanised APOE3 and APOE4 targeted replacement transgenic mouse model, the interactive influence of cocoa flavanols (FLAV) and APOE genotype on the blood and subcortical brain PUFA status following the supplementation of a high fat (HF) enriched with DHA from fish oil (FO) was investigated. DHA levels increased in the blood (p < 0.001) and brain (p = 0.001) following supplementation. Compared to APOE3, a higher red blood cell (RBC) DHA (p < 0.001) was evident in APOE4 mice following FO and FLAV supplementation. Although FO did not increase the percentage of brain DHA in APOE4, a 17.1% (p < 0.05) and 20.0% (p < 0.001) higher DHA level in the phosphatidylcholine (PC) fraction in the HF FO and HF FO FLAV groups, and a 14.5% (p < 0.05) higher DHA level in the phosphatidylethanolamine (PE) fraction in the HF FO FLAV group was evident in these animals relative to the HF controls. The addition of FLAV (+/- FO) did not significantly increase the percentage of brain DHA in the group as a whole. However, a higher brain: RBC DHA ratio was evident in APOE3 only (p < 0.05) for HF FLAV versus HF. In conclusion, our data shows only modest effects of FLAV on the brain DHA status, which is limited to APOE3.

Comparative effects of finasteride and laser-irradiated silver nanoparticles on testicular function and histology in testosterone induced benign prostatic hyperplasia in rats.

AIMS: The objective of this study was to compare the effects of finasteride, a medication used to treat benign prostatic hyperplasia (BPH), and laser irradiated silver nanoparticles (AgNPs), a potential candidate for BPH therapy (Sanchez-Salas, 2017; Marghani et al., 2022) [1,2], on the sex hormone profiles, sperm quality, steroidogenesis, testicular oxidative stress, and histomorphology changes in BPH rats. MATERIALS AND METHODS: BPH was induced in male Sprague-Dawley (SD) rats via intramuscular (i.m.) injection of 5 mg/kg BW testosterone propionate (TP) for 14 days. Once the BPH model was induced, rats were divided into four groups (n = 6) as follows: the control group; the BPH group; the BPH/Fina group, which received 5 mg/kg BW finasteride by oral gavage daily for 14 days; and the BPH/AgNPs group, which received a daily intraperitoneal (i.p.) injection of 50 mg/kg BW AgNPs, followed by 5min of exposure to a 532 nm NIR laser in the prostatic area for the constitutive 14 days. KEY FINDINGS: On day 14, the BPH rats had a significant increase in prostate specific antigen (PSA), dihydrotestosterone, and prostate weights, while testicular weights and sperm quality were significantly lower than in the control rats. On day 28, laser irradiated AgNps treated BPH rats showed improved sex hormone balance, testicular weights, sperm quality, steroidogenesis, and an ameliorative effect on testicular histopathology compared to finasteride. SIGNIFICANCE: Surprisingly, these findings suggest that laser irradiated AgNPs can be used as an alternative therapy to finasteride for the treatment of BPH without causing negative effects on the testes.

The combined effect of zinc oxide nanoparticles and milrinone on acute renal ischemia/reperfusion injury in rats: Potential underlying mechanisms.

AIM: To investigate the efficacy of zinc oxide nanoparticles (ZnO-NPs) and/or milrinone (MIL) on renal ischemia/reperfusion injury (I/RI) in rats and their possible underlying mechanisms. MATERIALS AND METHODS: Forty-eight adult male Sprague-Dawley albino rats were randomly assigned into six equal-sized groups (n = 8): normal control, sham-operated, I/R group (45 min/24 h), ZnO-NPs group (10 mg/kg i.p.), MIL group (0.5 mg/kg i.p.), and ZnO-NPs + MIL group in the same previous doses. KEY FINDINGS: In comparison to the I/R-operated group, administration of either ZnO-NPs or MIL significantly decreased serum creatinine and urea concentrations, and renal vascular permeability (p < 0.05). The oxidative stress was significantly declined, as evidenced by increased GPx, CAT, and SOD activities and decreased MDA and NO concentrations. Renal expressions of TNF-α, NF-κB, KIM-1, NGAL, and caspase-3 decreased significantly, while Nrf2 increased significantly. Histopathology investigation revealed improvement with minimal renal lesions and fibrosis after ZnO-NPs or MIL treatments. The combined treatments synergistically improved the studied parameters more than either treatment alone. These findings were validated by molecular modeling, which revealed that MIL inhibited TNF-α, NF-kB, caspase-3, KIM-1 and NGAL. SIGNIFICANCE: Both ZnO-NPs and MIL exerted cytoprotective effects against acute renal I/RI, and a combination of both was found to be even more effective. This renoprotective effect is suggested to be mediated through activation of Nrf2 and the prevention of the NF-κB activation-induced oxidative stress and inflammation, which may strengthen the potential role of ZnO-NPs or MIL in renal I/RI protection during surgical procedures.

Thiamethoxam evoked neural oxido-inflammatory stress in male rats through modulation of Nrf2/NF-kB/iNOS signaling and inflammatory cytokines: Neuroprotective effect of Silymarin.

Thiamethoxam (TMX), a neonicotinoid insecticide, is a widely used insecticide with neurotoxic potential. Silymarin (SM), a milk thistle-derived flavonoid, is known with its promising biological activities. This study explored the neuroprotective effects of SM against TMX-triggered cortical injury in male rats. Animals were divided into four groups and treated daily either with SM (150 mg/kg), TMX (78.15 mg/kg), or both at the aforementioned doses for 28 days. Our results revealed marked declines in cortical SOD and CAT activities with elevations in MDA, IL-1b and TNF-α levels in TMX-treated rats. Further, TMX induced down-regulation in the gene expressions of Sod, Cat, Gpx, and Nrf-2, with up-regulation in the gene expressions of IL-1b, IL-6, iNOS, TNF-α and NF-kB. Interestingly, pre-treatment with SM provided a notable neuroprotective action against TMX-mediated cortical damage that indicates its promising antioxidant and anti-inflammatory activities. This effect may be mediated by Nrf2/NF-kB/iNOS signalling and suppression of excess free radicals and production of inflammatory cytokines. In brief, SM could be a promising therapeutic agent against TMX-mediated neural complication via its antioxidant and anti-inflammatory properties. PRACTICAL APPLICATIONS: The using of neonicotinoids as thiamethoxam is recently increased and is associated with brain damage. TMX induced excessive oxidative and inflammatory damage. Therefore, new therapeutic approaches are needed to counteract its adverse effects on the nervous system. SM, a flavonoid, is extracted from the seeds and fruits of milk thistle. Due to its potent antioxidative activity, SM have been applied to mitigate the oxidative stress as well as inflammatory disorders. Herein, we examined the potential therapeutic role of SM against TMX-induced brain oxidative stress and inflammation in rats through evaluating oxidative markers, inflammatory response, and histopathological changes in the brain cortical tissue.

Growth-promoting and immunostimulatory effects of phytobiotics as dietary supplements for Pangasianodon hypophthalmus fingerlings.

A 56-day feeding experiment was designed to evaluate the impacts of five herbal extracts, namely Ginkgo biloba (GB), Moringa oleifera (MR), Myristica fragrans (NM), Silybum marianum (MT), and Astragalus membranaceus (AT) on growth, serum immune indices, and ammonia-N stress resistance of Pangasianodon hypophthalmus fingerlings. Fish were fed on a diet with no herbal additives (reference or CNT), and several plant extracts-based diets were supplied with two inclusion doses of each extract (1.0 and 2.0 g/kg). After the end of the feeding, fish in all groups were exposed to acute ammonia stress, mortalities were recorded every 2 h for a duration of 10 h, and then survival percent was assessed. Results showed that growth was upgraded significantly in groups fed plant extracts-based diets compared to the CNT group. Serum proteins (albumin and total protein), lysozyme, complement C3, bactericidal, and myeloperoxidase activities were increased significantly in groups fed plant extracts-based diets in relation to the CNT group. The total immunoglobulin levels were increased significantly only in fish groups fed GB, MT, and NM-based diets. Post-exposure to acute ammonia stress, the Kaplan-Meier survival curve presented significantly higher survival of fish groups that fed plant extracts-enriched diets than those fed the CNT diet. The aforementioned results suggest that using herbal extracts as feed supplements can beneficially enhance the growth, the immunity of P. hypophthalmus fingerlings and may increase their tolerance in the face of extrinsic stressors. These findings may pave the way for the potential and regular application of herbal extracts in diets of P. hypophthalmus at their early life stages to raise their immunity and maintain aquaculture sustainability.

Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer's Disease (EPAD) cohort.

BACKGROUND: The risk of dementia is higher in women than men. The metabolic consequences of estrogen decline during menopause accelerate neuropathology in women. The use of hormone replacement therapy (HRT) in the prevention of cognitive decline has shown conflicting results. Here we investigate the modulating role of APOE genotype and age at HRT initiation on the heterogeneity in cognitive response to HRT. METHODS: The analysis used baseline data from participants in the European Prevention of Alzheimer's Dementia (EPAD) cohort (total n= 1906, women= 1178, 61.8%). Analysis of covariate (ANCOVA) models were employed to test the independent and interactive impact of APOE genotype and HRT on select cognitive tests, such as MMSE, RBANS, dot counting, Four Mountain Test (FMT), and the supermarket trolley test (SMT), together with volumes of the medial temporal lobe (MTL) regions by MRI. Multiple linear regression models were used to examine the impact of age of HRT initiation according to APOE4 carrier status on these cognitive and MRI outcomes. RESULTS: APOE4 HRT users had the highest RBANS delayed memory index score (P-APOE*HRT interaction = 0.009) compared to APOE4 non-users and to non-APOE4 carriers, with 6-10% larger entorhinal (left) and amygdala (right and left) volumes (P-interaction= 0.002, 0.003, and 0.005 respectively). Earlier introduction of HRT was associated with larger right (standardized ß= -0.555, p=0.035) and left hippocampal volumes (standardized ß= -0.577, p=0.028) only in APOE4 carriers. CONCLUSION: HRT introduction is associated with improved delayed memory and larger entorhinal and amygdala volumes in APOE4 carriers only. This may represent an effective targeted strategy to mitigate the higher life-time risk of AD in this large at-risk population subgroup. Confirmation of findings in a fit for purpose RCT with prospective recruitment based on APOE genotype is needed to establish causality.

Study of electrical properties of cobalt oxide-doped sodium meta vanadate at different frequencies.

The samples were prepared within the binary system NaVO3-Co3O4 at different molar percentages depending on the ceramic method according to (x)NaVO3-(100-x)Co3O4, for the molar percentages (x = 5, 10, 25, 40, 60, 75, 80) mole%. The prepared samples were studied using X-rays diffraction (XRD), and their electrical properties were studied using LCR meter, such as the specific electrical resistivity ρ, electrical capacitance C, relative dielectric constant Ԑr, and loss tangent tanδ within the frequency range (10Hz-MHz). The results showed that the resistivity values of all the prepared samples increased, and the highest value is 2.91 × 10+07 (Ω.cm), in addition to the increase in the values of electrical capacitance and the highest value is 9.05 pF, the highest value of the relative dielectric constant is 28.39, and the highest value of the loss tangent is 7.01 × 10-2, with the change in the molar percentage of sodium meta vanadate in the samples.

RANK/RANKL/OPG axis genes relation to cognitive impairment in children with transfusion-dependent thalassemia: a cross-sectional study.

BACKGROUND: RANK/RANKL/OPG axis was implicated in many pathological conditions. The study aimed to assess the relationship between the studied RANK, RANKL, and OPG polymorphisms and alleles and cognitive impairment in children with transfusion-dependent thalassemia (TDT). METHODS: This study included 60 TDT children. Real-time PCR was done for: rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, rs9594782 and rs2277438 polymorphisms for the RANKL gene, and rs207318 polymorphism for the OPG gene. The intelligence quotient (IQ) was assessed using the Wechsler Intelligence Scale for Children-Third Edition. RESULTS: TDT children had a low average total IQ, verbal IQ, and borderline performance IQ. RANK rs1805034 (C > T) had a significant effect on total IQ (p = 0.03). Its TT polymorphism and the CT polymorphism of RANKL rs9494782 (C > T) had a significantly lower total IQ (p = 0.01 for both). The G allele of the RANKL rs2277438 (G > A) had a significantly lower total IQ (p = 0.02). RANK rs1805034 (C > T) and RANKL rs2277438 (G > A) significantly affected verbal IQ (p = 0.01 and 0.03). TT genotype of RANK rs1805034 (C > T) had significantly lower verbal IQ (p = 0.002). Furthermore, the GG genotype of RANKL rs2277438 (G > A) had a significantly lower verbal and performance IQ than the AA genotype (p = 0.04 and 0.01 respectively), and its G allele had a significantly lower performance IQ than the A allele (p = 0.02). CONCLUSION: TDT children had low average total and verbal IQ while their performance IQ was borderline. The RANK/RANKL/OPG pathway affects cognition in TDT children, as some of the studied genes' polymorphisms and alleles had significant effects on total, verbal, and performance IQ of the studied TDT children.

DHA-Enriched Fish Oil Ameliorates Deficits in Cognition Associated with Menopause and the APOE4 Genotype in Rodents.

Female APOE4 carriers have a greater predisposition to developing Alzheimer's disease (AD) compared to their male counterparts, which may partly be attributed to menopause. We previously reported that a combination of menopause and APOE4 led to an exacerbation of cognitive and neurological deficits, which were associated with reduced brain DHA and DHA:AA ratio. Here, we explored whether DHA-enriched fish oil (FO) supplementation mitigated the detrimental impact of these risk factors. Whilst DHA-enriched fish oil improved recognition memory (NOR) in APOE4 VCD (4-vinylcyclohexene diepoxide)-treated mice (p < 0.05), no change in spatial working memory (Y-maze) was observed. FO supplementation increased brain DHA and nervonic acid and the DHA:AA ratio. The response of key bioenergetic and blood−brain barrier related genes and proteins provided mechanistic insights into these behavioural findings, with increased BDNF protein concentration as well as mitigation of aberrant Erß, Cldn1 and Glut-5 expression in APOE4 mice receiving fish oil supplementation (p < 0.05). In conclusion, supplementation with a physiologically relevant dose of DHA-enriched fish oil appears to offer protection against the detrimental effects of menopause, particularly in "at-risk" APOE4 female carriers.

Photothermal therapeutic potency of plasmonic silver nanoparticles for apoptosis and anti-angiogenesis in testosterone induced benign prostate hyperplasia in rats.

AIMS: In this study, we used a near-infrared laser (NIR) to increase the potency of silver nanoparticles (AgNPs) to develop a novel, less invasive, and simple photothermal therapy technique for benign prostate hyperplasia (BPH). MATERIALS AND METHODS: The shape, particle size, and zeta-potential of polyvinylpyrrolidone coated-AgNPs (PVP-AgNPs) were determined using transmission electron microscopy (TEM), Zeta-potential, and Particle size analyzer (ELSZ). To induce BPH, thirty-six male Sprague-Dawley (SD) rats were given intramuscular (i.m) injections of testosterone propionate (TP) at 5 mg/kg body weight (b.w)/day suspended in 0.1 ml of olive oil for 14 days. Photothermal therapy with AgNPs-NIR for 14 days was carried out. Prostate size, prostate index (PI), dihydrotestosterone (DHT), prostate-specific antigen (PSA), gross, hepatic, and renal toxicity, as well as antioxidant activity, apoptosis, and angiogenesis markers in prostatic tissues were measured. Histological examinations of prostates and biocompatibility of NIR-AgNPs on vital organs were also performed. KEY FINDINGS: The aggregated spherical AgNPs with a mean size of 50-90 nm and a Zeta potential of -53.22 mV displayed high effectiveness in the NIR (532 nm-1 W) region by decreasing prostate size, PI, DHT, and PSA in BPH rats with no signs of gross, hepatic, or renal damage. As compared to alternative therapies, hyperthermia therapy increased antioxidant activities, induced apoptosis, inhibited angiogenesis, reduced histological alterations in the prostates of BPH rats, and improved biocompatibility of the vital organs. SIGNIFICANCE: The current study demonstrated the effectiveness of plasmonic AgNPs photothermal therapy in the treatment of BPH.

Fish, n-3 fatty acids, cognition and dementia risk: not just a fishy tale.

With growing and ageing populations, the incidence of dementia is expected to triple globally by 2050. In the absence of effective drugs to treat or reverse the syndrome, dietary approaches which prevent or delay disease onset have considerable population health potential. Prospective epidemiological studies and mechanistic insight from experimental models strongly support a positive effect of a high fish and long chain n-3 fatty acid (EPA and DHA) intake on a range of cognitive outcomes and dementia risk, with effect sizes equivalent to several years of ageing between the highest and lowest consumers. As reviewed here, an effect of EPA and DHA on neuroinflammation and oxylipin production is likely to in part mediate the neurophysiological benefits. However, randomised controlled trials (RCTs) with EPA and DHA supplementation have produced mixed findings. Insight into the likely modulators of response to intervention and factors which should be considered for future RCTs are given. Furthermore, the impact of APOE genotype on disease risk and response to EPA and DHA supplementation is summarised. The prevalence of dementia is several-fold higher in APOE4 females (about 13% Caucasian populations) relative to the general population, who are emerging as a subgroup who may particularly benefit from DHA intervention, prior to the development of significant pathology.

Perception and Awareness about Developmental Dysplasia of the Hip in Children among Pregnant Ladies in the Aseer Region, Southwestern Saudi Arabia.

Background: Developmental dysplasia of the hip (DDH) is classified as a group of malformations, varying from abnormal acetabulum (dysplasia) and mild subluxation of the femoral head to fixed displacement (congenital dislocation). This study aimed to assess the knowledge level and its determinants regarding DDH in children among pregnant females in the Aseer region of southwestern Saudi Arabia. Methods: A descriptive cross-sectional study was conducted targeting all pregnant females in the Aseer region between 1 February 2021 and 1 May 2021. A pre-structured online questionnaire was constructed by the researchers to obtain the participating females' bio-demographic data (including age, education status, and obstetric history) and awareness regarding DDH. The last section asked for their source of information regarding DDH. Results: A total of 253 pregnant females (aged between 18 and 45 years; mean age = 30.5 ± 10.2 years) fulfilling the inclusion criteria completed the study questionnaire. About 5% of the females reported having a child with DDH, and 166 (65.6%) pregnant females knew about DDH. Additionally, 110 (43.5%) females reported that they know about how DDH is treated, and 99 (39.1%) knew about DDH complications. The most commonly reported source of information was relatives and friends (44.3%), followed by social media (11.9%) and study and work (7.1%). Conclusions: Pregnant females in the Aseer region have poor knowledge and awareness about DDH and its causes, treatment modalities, and complications. Higher knowledge was associated with either high parity or having a child with DDH.

APOE Genotype Modifies the Plasma Oxylipin Response to Omega-3 Polyunsaturated Fatty Acid Supplementation in Healthy Individuals.

The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2, and 4 portions of oily fish per week for 12 months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE*n-3 PUFA dose effect was observed for the CYP-ω hydroxylase products 19-HEPE (p = 0.027) and 20-HEPE (p = 0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p = 0.014). Low basal plasma EPA levels (EPA < 0.85% of total fatty acids) were associated with a greater change in 5-HEPE, 9-HEPE, 11-HEPE, and 20-HEPE compared to high basal EPA levels (EPA > 1.22% of total fatty acids). In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for 12 months.