Search Results (2,718)

Shelter dogs may experience long-term environmental and social stressors that can affect their behaviour and welfare. Some individuals show reduced activity, low responsiveness to environmental stimuli, and limited interaction with their surroundings. This pilot study investigated behavioural patterns and allopregnanolone concentrations in shelter dogs exhibiting these behavioural characteristics. Ten shelter dogs were enrolled and divided into two groups: five dogs showing depression-like patterns and five matched control dogs. Each dog wore a three-axis accelerometer for 30 days to quantify activity levels. Behavioural observations were conducted using video recordings, and hair samples were collected at baseline and after 30 days to assess allopregnanolone concentrations as a potential stress marker. Dogs in the case group showed significantly longer resting time than controls (p ≤ 0.05), indicating reduced activity levels. Trends toward lower levels of exploratory and social behaviours were also observed, although the differences were not statistically significant. Allopregnanolone concentrations ranged from 0.6 to 4.6 pg/mg and showed considerable inter-individual variability, with no significant differences detected between groups. These findings provide preliminary evidence of behavioural and physiological alterations in shelter dogs displaying depression-like patterns. However, further studies with larger populations are needed to validate these findings and improve welfare assessment in shelter environments. Full article

Background/Objectives: Overweight and obesity have consistently increased in prevalence. Early exposure to foods high in fats and sugar through maternal conditions may increase vulnerability to developing metabolic diseases and cognitive impairments in adulthood. In this regard, we aim to evaluate the effects that perinatal exposure to cafeteria diet (CAF) and physical activity (PA) has on anxiety-like, depressive-like behavior, memory and diet preference in male and female offspring. Methods: Seventy female and male offspring rats were divided into five groups according to maternal conditions: (1) CONTROL, fed only standard diet (SD) with no voluntary PA, (2) SED+SD, fed only SD with no voluntary PA, (3) SED+CAF, fed SD and CAF with no voluntary PA, (4) PA+SD, fed only SD with voluntary PA, and (5) PA+CAF, fed SD and CAF with voluntary PA. Starting on PND 24, offspring rats were exposed to SD and CAF (except for rats from the CON maternal group) and evaluated for seven weeks for diet preference, and at week seven for anxiety-like, depressive-like behavior and memory. Results: After seven weeks of exposure to CAF, maternal conditions showed significantly different effects on adult male and female offspring for diet preference and memory impairments. Furthermore, maternal PA significantly reduced anxiety-like and depressive-like behaviors in the offspring. Conclusions: Our results suggest that maternal conditions and postweaning CAF exposure have a joint influence on diet preference, anxiety-like and depressive-like behavior. Additionally, perinatal CAF exposure impairs memory in male and female offspring, regardless of maternal PA conditions. However, maternal PA was associated with reduced affective behaviors induced by lifelong CAF, presenting as a promising non-pharmacological intervention to promote favorable long-term behavioral outcomes in offspring. Full article

Ruta graveolens L. fruits are densely covered with translucent dots corresponding to secretory cavities that accumulate bioactive metabolites, primarily essential oils. Immature fruits present an aromatic surface exudate, indicating the active release of secretory products despite the internal location of the cavities. This study investigated the origin, development, ultrastructure, and secretion-release mechanisms of fruit secretory cavities using light, scanning, and transmission electron microscopy. Secretory cavities originated from clusters of ground meristem cells associated with phloem strands. Lumen formation began with the collapse of central cells, while surrounding cells differentiated into a metabolically active secretory epithelium rich in polymorphic plastids, smooth endoplasmic reticulum, mitochondria, vesicles, and lipid bodies. Mature cavities consisted of a multilayered epithelium surrounding a large lumen and enclosed by a parenchymatous sheath. Progressive lysis of inner epithelial cells contributed to lumen expansion and secretion accumulation. As cavities enlarged, they became positioned immediately beneath the epidermis, whose cells became compressed and flattened. Secretion was released through the rupture of glandular and epidermal cells and through stomata located in epicarp depressions. Ultrastructural evidence indicates the combined operation of eccrine, granulocrine, and holocrine secretion mechanisms. Pectin–cellulosic wall thickenings likely function as apoplastic barriers, directing secretion toward the lumen and protecting adjacent tissues. Full article

Rs9939609 marker in FTO Alpha-Ketoglutarate-Dependent Dioxygenase (FTO) gene, rs7895307 in Transcription Factor 7-Like 2 (TCF7L2) gene, and rs75493593 in Solute Carrier Family 16 Member 11 (SLC16A11) gene have been associated with anthropometric, metabolic, and clinical variables, but have not been concurrently studied in Mexican children and adolescents with adiposity or mental disorders. In this cross-sectional association study, we genotyped these markers by means of TaqMan real-time polymerase chain reaction in two at-risk pediatric cohorts recruited in Mexico City. Group 1 (n = 175) comprised children and adolescents with overweight/obesity. Group 2 (n = 296) consisted of non-medicated adolescents meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for Attention Deficit/Hyperactivity Disorder or a mood disorder. Anthropometric measurements (body mass index —BMI—, waist circumference, body fat percentage), metabolic indices (fasting glucose, lipid profile, Homeostatic Model Assessment for Insulin Resistance), and psychiatric diagnoses were evaluated. In Group 1, the FTO A allele (genotypes AA/AT) was significantly associated with severe obesity according to BMI Z scores (p = 0.004, O.R. 3.33, 95% CI [1.42–7.77]), and it was a predictor of waist circumference (B = 6.16, 95% CI [1.78–10.55], p = 0.006) and muscle percentage (B = 4.21%, 95% CI [0.91–7.51%], p = 0.013) using linear regression models adjusted for age and sex. In Group 2, TCF7L2 AA genotype was associated with increased odds of depression (B = 0.83, p = 0.003, OR = 2.29, 95% CI [1.32–3.96]). While SLC16A11 G allele showed a possible association with insulin resistance or glucose levels, confirmation is needed. These exploratory results highlight the need for larger, well characterized cohort studies to confirm the associations. Full article

Inflammatory bowel disease is an inflammatory disorder associated with systemic immune activation, contributing to neuroinflammation, behavioral impairments and disruption of the gut–brain axis. The present study investigated the effects of p-Coumaric acid derivatives: Artepillin C (ART-C), Baccharin (BAC), and Drupanin (DRU) on colonic damage, behavioral alterations, and oxidative stress in a dextran sulfate sodium (DSS)-induced colitis by administration of 3% DSS. Mice were treated with p-Coumaric acid derivatives (0.3, 1, or 3 mg/kg, p.o.), and disease activity index and colon length were evaluated as clinical parameters. Behavioral assessments included the open field test, novel object recognition test, elevated plus maze, and tail suspension test. Oxidative stress and inflammatory markers were quantified in colon, serum, cortex, and hippocampus, alongside histological analysis of colonic tissue. DSS administration induced clinical and histopathological alterations, increased oxidative stress, and impaired recognition memory, as well as anxiety- and depressive-like behaviors. p-Coumaric acid derivatives attenuated colonic damage, preserved tissue architecture, improved recognition memory, and reduced anxiety- and depressive-like behaviors, particularly at higher doses. These effects were associated with modulation of antioxidant defenses and reduction of lipid peroxidation and inflammatory markers. p-Coumaric acid derivatives exert protective effects in DSS-induced colitis, highlighting their potential as therapeutic agents for intestinal and neurobehavioral alterations associated with IBD. Full article

Sugarcane polyphenols (SP) are investigated for their antidepressant potential using a CUMS-induced mouse model and a corticosterone-induced neuronal injury cell model. Results demonstrate that SP alleviates depressive-like behaviors, inhibits hippocampal neuronal apoptosis, and reduces neuroinflammation. Mechanistically, SP activates the MAPK/ERK pathway, which in turn suppresses NLRP3 inflammasome-mediated pyroptosis; this effect is attenuated by the MAPK/ERK inhibitor PD98059. Furthermore, SP synergizes with the caspase-1 inhibitor VX-765 to inhibit pyroptosis. Full article

Background: Adolescence is a sensitive period for brain maturation during which exposure to Δ⁹-tetrahydrocannabinol (THC) can induce long-lasting neurobehavioral alterations. Yet, preclinical and clinical studies report inconsistent long-term outcomes of adolescent THC exposure, ranging from clear impairments to apparently normalizing effects. We hypothesize that these discrepancies reflect stable individual differences in stress-coping abilities. Methods: To test this, selectively bred Dominant (Dom; stress-resilient, risk-prone) and Submissive (Sub; stress-vulnerable, depressive-like) Sabra mice received THC or vehicle during adolescence and were assessed in adulthood. Results: Anxiety-like and exploratory behavior, measured in the hole-board test, were differentially affected by THC as a function of stress vulnerability: in Sub mice, THC increased exploration and reduced anxiety-like behavior, whereas in Dom mice THC produced the opposite pattern. Recognition memory, evaluated by the novel object recognition test, showed modest, line-dependent alterations. Sensitivity to N-methyl-D-aspartate (NMDA) receptor hypofunction, a widely used index of vulnerability to schizophrenia-like symptoms, was examined using MK-801-induced locomotion. Adolescent THC potentiated MK-801-evoked hyperlocomotion in Dom mice but attenuated it in Sub mice. Conclusions: In the context of increasing medical and recreational cannabis exposure, these in vivo findings suggest that stress-vulnerability-related traits may be an important variable to consider in future preclinical and translational studies of adolescent THC exposure. Full article

Background and Objectives: Cardiac implantable electronic devices (CIEDs), including permanent pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices, are increasingly used in an aging population characterized by multimorbidity and a high prevalence of psychiatric and cognitive disorders. Depression, anxiety, post-traumatic stress disorder (PTSD), mild cognitive impairment, and dementia may affect informed consent, adherence to therapy, quality of life, and long-term cardiovascular outcomes in patients undergoing CIED implantation. The aim of this review was to summarize the prevalence and clinical significance of psychiatric and cognitive disorders in patients undergoing CIED implantation and to discuss practical strategies for their assessment in routine cardiology practice. Materials and Methods: This narrative review was based on a literature search of PubMed, Web of Science, and the National Health Library database covering the literature from 2010 to 2025, including a broad search strategy. Original studies and review articles were included, having confirmed their definite association with the subject. Results: Psychiatric disorders and cognitive impairment were highly prevalent among patients with CIEDs and were associated with impaired adherence, reduced participation in rehabilitation, lower quality of life, and worse cardiovascular outcomes. ICD therapies, particularly inappropriate therapies, were strongly associated with anxiety, depressive symptoms, and PTSD-related distress. Cognitive impairment may compromise informed consent, recognition of complications, and compliance with post-implantation recommendations. Several validated screening tools, including MMSE, MoCA, HADS, BDI-II, STAI, and FSAS, may facilitate early identification of high-risk patients, and their most appropriate use in various clinical scenarios, including pre- and post-CIED implantation was described. Conclusions: Psychiatric disorders and cognitive impairment are common and clinically relevant in patients undergoing CIED implantation. Routine psychological and cognitive assessment before and after implantation should be considered an important component of modern multidisciplinary cardiac care, potentially affecting the decision to implant the device, and likely influencing the type of the implanted device. Full article

The COVID-19 pandemic highlighted the urgent need to develop effective and broad-spectrum antiviral therapies against coronaviruses. One strategy to address this concern is a combination therapy using repurposed drugs against zoonotic viruses with pandemic potential. We previously demonstrated that the combination of Remdesivir and Ivermectin is highly potent and synergistic in inhibiting the replication of murine hepatitis virus (MHV) in RAW264.7 macrophages. This study investigated the interactions between the drug combination, coronavirus and host by proteomics and RNA sequencing of MHV-infected H2.35 murine liver epithelial cells. Time-of-addition and time-of-removal assays suggested that the drug combination likely affected the synthesis of viral RNA and viral protein. This combination drastically diminished the live virus titer greater than the respective monotherapies in MHV-infected H2.35 cells (by ~4 log₁₀), as well as in SARS-CoV-2-infected VeroE6 cells and human nasal epithelial cells. Proteomic and transcriptomic analyses revealed that viral protein and RNA levels were significantly depressed upon combination treatment. The drug combination exhibited considerable negative effects upon host RNA processes and resulted in the upregulation of host protein processes (e.g., response to unfolded protein; protein insertion into ER membrane). Molecular pathways affected by the combination treatment were markedly distinct from the monotherapies and indicated that Ivermectin enhances Remdesivir by modulating critical host processes to synergistically exert its inhibitory effect on the coronavirus replication cycle. Full article

Background: Schizophrenia is a chronic neuropsychiatric disorder characterized by cognitive impairment, behavioral abnormalities, neuroinflammation, and oxidative stress. Increasing evidence suggests that dysregulated inflammatory cytokines and impaired antioxidant defenses contribute to schizophrenia pathophysiology. This study investigated the neuroprotective and anti-inflammatory effects of Gallic Acid (GA) in a ketamine-induced experimental schizophrenia model. Methods: Thirty male Balb/C mice were randomly divided into control, ketamine, and ketamine + GA groups. Schizophrenia was induced with ketamine (25 mg/kg/day) for 7 days, while the treatment group additionally received GA (60 mg/kg/day) for another 7 days. Behavioral tests, including open field, novel object recognition, and tail suspension tests, were performed to evaluate locomotor activity, cognition, and depressive-like behavior. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-18 (IL-18), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), and total oxidant status (TOS) levels were analyzed in hippocampal and prefrontal cortex tissues to assess inflammatory and oxidative stress-related alterations. Results: Ketamine induced schizophrenia-like behaviors, including hyperlocomotion, memory impairment, and increased immobility. These behavioral alterations were accompanied by significantly elevated TNF-α, IL-1β, IL-18, and TOS levels, alongside reduced SOD, CAT, GSH-Px, and TAS levels in the hippocampus and prefrontal cortex. GA treatment ameliorated behavioral impairments, restored antioxidant enzymes, increased TAS levels, and reduced pro-inflammatory cytokines and TOS in these brain regions. Conclusions: GA exerted neuroprotective effects in the ketamine-induced schizophrenia model by reducing oxidative stress, neuroinflammation, and behavioral deficits. These findings suggest that Gallic Acid may serve as a promising therapeutic candidate for schizophrenia through modulation of inflammatory and oxidative stress pathways. Full article

Chronic sleep deprivation (SD) disrupts gut–brain axis (GBA) homeostasis and is closely associated with gut microbiota dysbiosis, neuroinflammation, and depression-like behaviors. This study investigated whether fermentation enhances the antidepressant-like effects of Dendrobium officinale by comparing fermented Dendrobium officinale (FDO) with unfermented Dendrobium officinale (DO) in a chronic SD mouse model. FDO significantly ameliorated anxiety and depressive-like behaviors in SD mice. It reshaped gut microbial structures, enriched beneficial bacteria taxa such as Dubosiella, [Eubacterium]_coprostanoligenes_group, and Allobaculum, and increased SCFA levels. FDO also enhanced colonic ZO-1 and Occludin expression and reduced serum levels of LPS and the pro-inflammatory cytokines. At the central nervous system level, FDO inhibited the activation of hippocampal microglia and astrocytes; alleviated neuroinflammation; restored hippocampal TPH2, 5-hydroxytryptamine (5-HT), and 5-HIAA levels; and modulated the 5-HT_1A/5-HT_2A receptor balance. In addition, FDO upregulated BDNF, PSD-95, and SYN expression and reduced corticosterone (CORT) levels. Compared with DO, FDO showed more pronounced regulatory effects. Correlation analysis suggested that 5-HT may link gut microbial metabolites, inflammation, and synaptic plasticity. In summary, these findings support FDO as a potential GBA-targeted functional food for SD-related depressive-like behaviors. Full article

Background/Objectives: Loneliness is a relevant social determinant of health in older age and has been associated with adverse physical, psychological and social outcomes. This study aimed to estimate the prevalence of severe loneliness and to identify its epidemiological and clinical correlates among community-dwelling older adults at risk of falls in Andalusia, Spain. Methods: A cross-sectional analytical study was conducted with 237 adults aged 65 years and older living in private households. Loneliness was assessed using the 10-item version of the UCLA Loneliness Scale, which showed excellent internal consistency in this sample (Cronbach’s alpha = 0.900). After reviewing the scoring direction of the instrument, severe loneliness was operationally defined using the corrected UCLA total score, with higher scores indicating greater loneliness. Sociodemographic and clinical variables included age, sex, living arrangements, economic level, family relationships, pain, sleep quality, depression history, physical exercise, outings from home, polymedication and analgesic use. Bivariate analyses were performed to compare participants with and without severe loneliness, and logistic regression was used to examine independent correlates of severe loneliness. Results: Severe loneliness was identified in 51 participants, corresponding to 21.5% of the analytical sample. The corrected UCLA-10 loneliness burden score ranged from 0 to 30, with higher scores indicating greater loneliness. Participants with severe loneliness were more likely to report poorer sleep quality and severe pain. In the adjusted logistic regression model including age, sex, sleep quality and severe pain, better sleep quality was associated with lower odds of severe loneliness (OR = 0.46, 95% CI: 0.30–0.72, p = 0.001), while severe pain was associated with higher odds of severe loneliness (OR = 3.15, 95% CI: 1.56–6.35, p = 0.001). Age (OR = 1.03, 95% CI: 0.99–1.07, p = 0.184) and female sex (OR = 2.00, 95% CI: 0.83–4.81, p = 0.124) were not statistically significant in the fully adjusted model. Conclusions: Severe loneliness affected a clinically relevant proportion of community-dwelling older adults at risk of falls in Andalusia. The findings should be interpreted as cross-sectional associations and not as evidence of causal pathways. Sleep quality and severe pain emerged as the main independent clinical correlates of severe loneliness in the adjusted model, supporting the relevance of multidimensional assessment in frail older adults. Full article

As the global population continues to age, mental health issues such as depression, anxiety, stress, loneliness, and social isolation among older adults are receiving increasing attention. The built environment is closely associated with older adults’ daily mobility, environmental perception, social participation, and mental health and well-being, but the evidence remains heterogeneous across spatial contexts, environmental indicators, and study designs. Previous umbrella reviews have summarized broad links between the built environment and healthy aging, but less attention has been paid to recent original empirical studies published after the COVID-19 pandemic, the distinction between objective environmental exposure and subjective environmental perception, and the role of social participation as a pathway linking environmental conditions to mental health and well-being. This study employs a systematic literature review approach, searching and screening peer-reviewed empirical studies published between 2015 and January 2026 that focus on the associations between the built environment and older adults’ mental health and well-being. PubMed, Scopus, and Web of Science databases were used for searching, supplemented by manual searching. After title and abstract screening and full-text evaluation, a total of 60 studies were included. Subsequently, a comprehensive analysis was conducted on aspects such as research design, spatial scale, environmental indicators, types of mental health outcomes, and potential pathways of action. In this review, core mental health and well-being outcomes included negative outcomes, such as depression, anxiety, stress, psychological distress, loneliness, and social isolation, and positive outcomes, such as life satisfaction, subjective well-being, psychological well-being, and mental well-being. Social participation was examined as a behavioral and psychosocial pathway rather than as a core outcome. Emerging methods, including street-view image analysis, FCN-based semantic segmentation, and XGBoost-SHAP, were examined because they can refine environmental exposure measurement and support variable-importance interpretation, rather than because they provide causal evidence. The main synthesis suggests that several built environment factors are associated with older adults’ mental health and well-being, although the strength and consistency of evidence vary across outcome types, spatial contexts, and study designs. (1) Exposure to green and blue spaces, quality of public open spaces, walkability and accessibility, accessibility of neighborhood facilities and services, housing and living conditions, and positive environmental perception are mostly associated with lower levels of depression, anxiety, stress, and loneliness, as well as higher levels of life satisfaction, subjective well-being, and psychological well-being. (2) Conversely, adverse environmental exposures such as proximity to roads, pollution, non-vegetated spaces, and high-intensity urbanization are more likely to exacerbate negative psychological outcomes. Existing evidence also suggests that social participation is one of the important behavioral pathways through which the built environment is linked to the mental health of older adults, but it is not the only mechanism. (3) In addition, the direction and intensity of environmental associations remain heterogeneous under different spatial scales, indicator types, and research methods. Overall, this review contributes by organizing recent empirical evidence into a built environment–social participation–mental health and well-being framework, while emphasizing that most findings should be interpreted primarily as evidence of association rather than as stable or uniform causal effects. Full article

Chronic depression is associated with oxidative stress, neuroinflammation, neurotransmitter imbalance, and Alzheimer’s-like changes. Current monoamine oxidase inhibitors have limited cognitive benefits and disease-modifying properties. A new nanotherapeutic, combining chitosan nanoparticles, propargylamino-1-(4-methylthiophenyl) propane (PAMTP), and L-tyrosine (En@PAMTP_Tyr), was developed. En@PAMTP_Tyr nanoparticles were ~140 nm in diameter, with a zeta potential of +27 mV and entrapment efficiencies of 73.45% for PAMTP and 90.85% for L-tyrosine. Drug release was pH-sensitive, favoring acidity. Intraperitoneal administration of En@PAMTP_Tyr reduced anhedonia, despair, cognitive deficits, and neuromuscular weakness, with efficacy matching or exceeding that of selegiline. In treated rats’ hippocampal tissue, En@PAMTP_Tyr increased superoxide dismutase and glutathione, normalized MAO and acetylcholinesterase activities, and corrected CUSD-induced TNF-α and IL-10 changes, showing antioxidant and anti-inflammatory effects. Histological analyses revealed that En@PAMTP_Tyr preserved CA1 pyramidal neurons, reduced β-amyloid levels, restored tau protein, and improved brain-derived neurotrophic factor levels, indicating reduced neurodegeneration. Molecular docking studies showed that PAMTP had high affinity for monoamine oxidase and acetylcholinesterase, supporting its role as an MAO-B inhibitor and cholinergic modulator. These findings suggest that En@PAMTP_Tyr is a promising nanoplatform for targeting MAO-B in depression, addressing mood, cognitive function, oxidative stress, inflammation, and Alzheimer-like pathology in the hippocampus. Full article

Adolescents with LGBTQ+ parents and LGBTQ+ adolescents navigate unique social and identity-related challenges as compared to those without minoritized sexual and/or gender identities. Adolescents with LGBTQ+ parents (regardless of their own sexual or gender identity) and adolescents who personally identify as LGBTQ+ are distinct populations, though they sometimes overlap. Research on adolescents with LGBTQ+ parents has often focused on parent–adolescent relationships and family structures. How do friends help youth cope with identity-based minority stressors, like peer microaggressions, bullying, and exclusion, common for those with minoritized identities? Friendships are developmentally pivotal during adolescence, shaping social competence, identity exploration, and psychological adjustment. Grounded in ecological systems, social learning, and minority stress theories, we sought to understand how friendships relate to mental health and coping in adolescents with LGBTQ+ parents. This cross-sectional quantitative study included 98 adolescents (ages 12–19) with LGBTQ+ parents in the U.S., recruited via community sampling and Prolific. Higher-quality peer attachment, conceptualized by trust, communication, and alienation in close friendships, was associated with lower depression and greater social competence, but not associated with anxiety or adaptive coping (after accounting for avoidant coping). Avoidant coping was most strongly associated with poorer mental health. This study, with implications for practice, emphasizes the importance of peer relationships for adolescents with LGBTQ+ parents—particularly how high-quality friendships offer important possible protection via social competence and against depression—while also highlighting the complex interplay between friendships, coping, and adjustment. Full article