Recently, functional foods have been considered as an effective approach in management of type 2 diabetes mellitus. This trial aimed to evaluate the potential benefits of date seed powder (DSP) on inflammation anxiety- and depression-like behaviours, sleep quality and tryptophan (TRP)–kynurenine (KYN) metabolism in type 2 diabetes mellitus patients. In this trial, forty-three patients with type 2 diabetes were randomised to two groups: either 5 g/d of the DSP or placebo for 8 weeks. Depression, anxiety and stress scale, sleep quality, quality of life (QoL), levels of fasting blood glucose, endotoxin, anti-inflammatory/pro-inflammatory biomarkers, hypothalamus–pituitary–adrenal (HPA) axis-associated biomarkers (including brain-derived neurotrophic factor (BDNF)), KYN, TRP, cortisol and adrenocorticotropic hormone (ACTH) were assessed at baseline and after 8 weeks. An independent t test was used for baseline comparisons, while ANCOVA was used for post-intervention between-group comparisons. The results showed that supplementation with DSP significantly improved depression, anxiety and stress scale, sleep quality and QoL in comparison with placebo. In terms of biochemical parameters, the intervention group exhibited significantly reduced levels of endotoxin, and cortisol, KYN, KYN:TRP ratio as well as significantly elevated levels of IL-10, TRP concentrations and IL-10:IL-18 ratio compared to the placebo group. Changes in fasting sugar, C-reactive protein (hs-CRP), IL-18, ACTH, BDNF concentrations and cortisol:ACTH ratio were not different between groups. Supplementing with date seed may effectively improve anxiety- and depression-like behaviours, sleep quality and QoL by modulating metabolic endotoxemia, inflammation and HPA axis activity in patients with type 2 diabetes.

Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR)T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA) (ORT3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed (P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increased by 20% (OR = 1.20, 95% CI = 1.01–1.43) for each standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression (Pnonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.

Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.

Brain ageing, the primary risk factor for cognitive impairment, occurs because of the accumulation of age-related neuropathologies. Identifying effective nutrients that increase cognitive function may help maintain brain health. Tomatoes and lemons have various bioactive functions and exert protective effects against oxidative stress, ageing and cancer. Moreover, they have been shown to enhance cognitive function. In the present study, we aimed to investigate the effects of tomato and lemon ethanolic extracts (TEE and LEE, respectively) and their possible synergistic effects on the enhancement of cognitive function and neurogenesis in aged mice. The molecular mechanisms underlying the synergistic effect of TEE and LEE were investigated. For the in vivo experiment, TEE, LEE or their mixture was orally administered to 12-month-old mice for 9 weeks. A single administration of either TEE or LEE improved cognitive function and neurogenesis in aged mice to some extent, as determined using the novel object recognition test and doublecortin immunohistochemical staining, respectively. However, a significant enhancement of cognitive function and neurogenesis in aged mice was observed after the administration of the TEE + LEE mixture, which had a synergistic effect. N-methyl-d-aspartate receptor 2B, postsynaptic density protein 95, and brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB)/extracellular signal-regulated kinase (ERK) phosphorylation also synergistically increased after the administration of the mixture compared with those in the individual treatments. In conclusion, compared with their separate treatments, treatment with the TEE + LEE mixture synergistically improved the cognitive function, neurogenesis and synaptic plasticity in aged mice via the BDNF/TrkB/ERK signalling pathway.

Maternal antenatal anxiety is an emerging risk factor for child emotional development. Both sex and epigenetic mechanisms, such as DNA methylation, may contribute to the embedding of maternal distress into emotional outcomes. Here, we investigated sex-dependent patterns in the association between antenatal maternal trait anxiety, methylation of the brain-derived neurotrophic factor gene (BDNF DNAm), and infant negative emotionality (NE). Mother–infant dyads (N = 276) were recruited at delivery. Maternal trait anxiety, as a marker of antenatal chronic stress exposure, was assessed soon after delivery using the Stait-Trait Anxiety Inventory (STAI-Y). Infants’ BDNF DNAm at birth was assessed in 11 CpG sites in buccal cells whereas infants’ NE was assessed at 3 (N = 225) and 6 months (N = 189) using the Infant Behavior Questionnaire-Revised (IBQ-R). Hierarchical linear analyses showed that higher maternal antenatal anxiety was associated with greater 6-month-olds’ NE. Furthermore, maternal antenatal anxiety predicted greater infants’ BDNF DNAm in five CpG sites in males but not in females. Higher methylation at these sites was associated with greater 3-to-6-month NE increase, independently of infants’ sex. Maternal antenatal anxiety emerged as a risk factor for infant’s NE. BDNF DNAm might mediate this effect in males. These results may inform the development of strategies to promote mothers and infants’ emotional well-being.

Patients with neuropathic pain are heterogeneous in pathophysiology, etiology, and clinical presentation. Signs and symptoms are determined by the nature of the injury and factors such as genetics, sex, prior injury, age, culture, and environment. Basic science has provided general information about pain etiology by studying the consequences of peripheral injury in rodent models. This is associated with the release of inflammatory cytokines, chemokines, and growth factors that sensitize sensory nerve endings, alter gene expression, promote post-translational modification of proteins, and alter ion channel function. This leads to spontaneous activity in primary afferent neurons that is crucial for the onset and persistence of pain and the release of secondary mediators such as colony-stimulating factor 1 from primary afferent terminals. These promote the release of tertiary mediators such as brain-derived neurotrophic factor and interleukin-1β from microglia and astrocytes. Tertiary mediators facilitate the transmission of nociceptive information at the spinal, thalamic, and cortical levels. For the most part, these findings have failed to identify new therapeutic approaches. More recent basic science has better mirrored the clinical situation by addressing the pathophysiology associated with specific types of injury, refinement of methodology, and attention to various contributory factors such as sex. Improved quantification of sensory profiles in each patient and their distribution into defined clusters may improve translation between basic science and clinical practice. If such quantification can be traced back to cellular and molecular aspects of pathophysiology, this may lead to personalized medicine approaches that dictate a rational therapeutic approach for each individual.

Major depressive disorder (MDD) is regarded as an inflammatory disorder. Gut microbiota dysbiosis, observed in both MDD and obesity, leads to endotoxemia and inflammatory status, eventually exacerbating depressive symptoms. Manipulation of gut microbiota by prebiotics might help alleviate depression. The present study aimed to investigate the effects of inulin supplementation on psychological outcomes and biomarkers of gut permeability, endotoxemia, inflammation, and brain-derived neurotrophic factor (BDNF) in women with obesity and depression on a calorie-restricted diet. In a double-blind randomised clinical trial, forty-five women with obesity and MDD were allocated to receive 10 g/d of either inulin or maltodextrin for 8 weeks; all the patients followed a healthy calorie restricted diet as well. Anthropometric measures, dietary intakes, depression, and serum levels of zonulin, lipopolysaccharide (LPS), inflammatory biomarkers (TNF-α, IL-10, monocyte chemoattractant protein-1, toll-like receptor-4 and high-sensitivity C-reactive protein), and BDNF were assessed at baseline and end of the study. Weight and Hamilton Depression Rating Scale (HDRS) scores decreased in both groups; between-group differences were non-significant by the end of study (P = 0·333 for body weight and P = 0·500 for HDRS). No between-group differences were observed for the other psychological outcomes and serum biomarkers (P > 0·05). In this short-term study, prebiotic supplementation had no significant beneficial effects on depressive symptoms, gut permeability, or inflammatory biomarkers in women with obesity and depression.

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

The progression of cardiometabolic diseases is determined by both genetic and environmental factors. Gene–diet interactions may therefore be important in modulating the risks of developing metabolic diseases. The objectives were to investigate the effect of the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms and dietary insulin index (DII) and dietary insulin load (DIL) on cardiometabolic markers among diabetic patients. In this cross-sectional study, blood samples were collected from 667 patients. DIL and DII were defined using a validated FFQ. Genotyping the BDNF Val66Met polymorphism was conducted by the PCR-Restriction fragment length polymorphism (RFLP) method. Interactions between dietary indices and gene variants were evaluated using a generalised linear model. PGF2a concentrations were significantly higher among Val homozygotes than Met-allele carrier. This study revealed that, compared with individuals with the Val/Val genotype, those with the Met/Val or Met/Met genotype had lower BMI (Pinteraction = 0·04), TAG (Pinteraction = 0·04), leptin (Pinteraction = 0·01), LDL (Pinteraction = 0·04) and total cholesterol (Pinteraction = 0·01) when they consumed diets higher on the DIL index. Moreover, the highest quartile of the DIL, compared with the lowest, showed increase in waist circumference (Pinteraction = 0·02) and LDL/HDL (Pinteraction = 0·04) for Val/Val homozygotes compared with Met-allele carriers. BDNF Val66Met variants may interact with DIL and DII, thus be involved in the development of cardiometabolic risk factors. If diabetic patients with Met alleles regulate dietary intakes, they have a protective opportunity to regulate their cardiometabolic markers.

Fructose (C6H12O6), also known as levulose, is a hexose. Chronic consumption of fructose may be associated with increased intrahepatic fat concentration and the development of insulin resistance as well as an increase in the prevalence of nonalcoholic fatty liver disease and hyperlipidemia during pregnancy. Despite the existence of many studies regarding the consumption of fructose in pregnancy, its effects on fetuses have not yet been fully elucidated. Therefore, the objective of this study was to evaluate the genetic and biochemical effects in offspring (male and female) of female mice treated with fructose during pregnancy and lactation. Pairs of 60-day-old Swiss mice were used and divided into three groups; negative control and fructose, 10%/l and 20%/l doses of fructose groups. After offspring birth, the animals were divided into six groups: P1 and P2 (males and females), water; P3 and P4 (males and females) fructose 10%/l; and P5 and P6 (males and females) fructose 20%/l. At 30 days of age, the animals were euthanized for genetic and biochemical assessments. Female and male offspring from both dosage groups demonstrated genotoxicity (evaluated through comet assay) and oxidative stress (evaluated through nitrite concentration, sulfhydril content and superoxide dismutase activity) in peripheral and brain tissues. In addition, they showed nutritional and metabolic changes due to the increase in food consumption, hyperglycemia, hyperlipidemia, and metabolic syndrome. Therefore, it is suggested that high consumption of fructose by pregnant female is harmful to their offspring. Thus, it is important to carry out further studies and make pregnant women aware of excessive fructose consumption during this period.

Although the long-term effects of a Mediterranean-style dietary pattern (MDP) on cognition and overall mental well-being have been consistently described, the short-term effects of the MDP on cognitive performance, mood and anxiety have not been as widely reviewed. Therefore, the aims of this systematic review were to synthesise the evidence from randomised controlled trials (RCT), to examine whether a MDP can alter cognition and overall mental well-being in the short-term (up to 10 d). This will also be used to identify research gaps and to inform the design of future acute RCT in the area. Ovid Embase, Ovid MEDLINE and Web of Science Core Collection were searched from inception to 8 December 2020. The data were synthesised narratively with no quantitative synthesis. The detailed protocol is available on PROSPERO, with the registration number CRD42021221085. A total of 3002 studies were initially identified. After the deduplication and screening stages, four studies (three articles and one conference proceeding) were eligible to be included. Despite the very limited data obtained, the literature suggests that a MDP can improve cognition and mood in the short-term. Specifically, improvements in attention, alertness and contentment were consistently reported. A MDP appears as a promising strategy to improve short-term cognitive and mental health. A limitation of this review is the small number of studies identified; therefore, future studies are required to confirm these initial novel findings and to provide granularity as to which domains are most responsive and in which population subgroups.

Neuropsychiatric disorders are major causes of the global burden of diseases, frequently co-occurring with multiple co-morbidities, especially obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and its various risk factors in the metabolic syndrome. While the determining factors of neuropsychiatric disorders are complex, recent studies have shown that there is a strong link between diet, metabolic state and neuropsychiatric disorders, including anxiety and depression. There is no doubt that rodent models are of great value for preclinical research. Therefore, this article focuses on a rodent model of chronic consumption of high-fat diet (HFD), and/or the addition of a certain amount of cholesterol or sugar, meanwhile, summarising the pattern of diet that induces anxiety/depressive-like behaviour and the underlying mechanism. We highlight how dietary and metabolic risk influence neuropsychiatric behaviour in animals. Changes in dietary patterns, especially HFD, can induce anxiety- or depression-like behaviours, which may vary by diet exposure period, sex, age, species and genetic background of the animals used. Furthermore, dietary patterns significantly aggravate anxiety/depression-like behaviour in animal models of neuropsychiatric disorders. The mechanisms by which diet induces anxiety/depressive-like behaviour may involve neuroinflammation, neurotransmitters/neuromodulators, neurotrophins and the gut–brain axis. Future research should be focused on elucidating the mechanism and identifying the contribution of diet and diet-induced metabolic risk to neuropsychiatric disorders, which can form the basis for future clinical dietary intervention strategies for neuropsychiatric disorders.