Search Results (598)

Although conventional medicine has seen substantial progress in recent years, there is a growing interest in nutraceuticals, bioactive compounds derived from natural sources such as plants, fruits, and cereals, due to their potential therapeutic applications. These substances have garnered increasing attention for their capacity to support ocular health and to aid in the prevention and management of age-related eye disorders, including age-related macular degeneration (AMD), cataracts, and glaucoma. This review provides a comprehensive and detailed analysis of selected nutraceuticals related to ocular health and diseases. It aims to define their pharmacodynamic properties, to elucidate the molecular and cellular mechanisms underlying their effects and to critically evaluate the current evidence regarding their potential clinical applications. By integrating findings from both preclinical and clinical studies, this review seeks to offer insights into the role of these nutraceuticals in the prevention, management, and adjunctive treatment of various ocular disorders, thereby suggesting future research directions and clinical practice. Notable attention is given to their antioxidant, anti-inflammatory, and neuroprotective properties, which are believed to contribute to the preservation of visual function and the deceleration of disease progression. Elucidating the medicinal benefits of these compounds may open new pathways for complementary or alternative strategies in the prevention and treatment of ocular diseases. Full article

Perfluorooctane sulfonate (PFOS), a member of the per- and polyfluoroalkyl substance (PFAS) family, has been associated with adverse health effects, including potential links to autism spectrum disorder (ASD). This study investigates the impact of PFOS on metabolic, immunologic and behavioral profiles in BTBR-mt^B6 mice, a mouse strain that models ASD, to provide insights into the role of PFOS in ASD development and related health concerns. Three-month-old male and female BTBR-mt^B6 mice were divided into two groups (n = 6) and received daily administration of either 1 mg/kg PFOS or vehicle over a three-month period by gavage. Metabolic assessments included measurements of body weight and weekly blood glucose levels, glucose and insulin tolerance tests, organ weights, and body compositions (free fluid, fat and lean tissue). Immune profiling was conducted via flow cytometric analysis of splenic leukocytes, while behavioral evaluations included grooming, sniffing, and three-chamber social interaction tests. PFOS exposure disrupted glucose homeostasis, with both sexes exhibiting elevated blood glucose levels. Male mice showed impaired glucose tolerance, delayed glucose level recovery, and increased insulin resistance, while females displayed decreased insulin resistance. Additionally, PFOS exposure led to liver enlargement in both sexes. Behavioral assessments revealed heightened grooming in PFOS-treated males, commonly interpreted as stress- or ASD-related repetitive behaviors, whereas females exhibited reduced grooming, reflecting altered behavioral responses to exposure. Immune alterations were also sex specific. PFOS-treated males exhibited decreased granulocytes, increased macrophages, and enhanced surface expressions of B220 and CD40L. PFOS-treated females showed increased macrophages, B-cells, cytotoxic T-cells and CD25⁺ T-cell subsets, with enhanced surface expression of B220 and CD8, and reduced surface expression of Mac-3. In addition, PFOS exposure reduced spleen weight in females. Taken together, PFOS exposure induced significant physiological and behavioral changes in BTBR-mt^B6 mice, with sex-specific differences observed. These results raise concern that PFASs may contribute to the development or exacerbation of metabolic, immune and neurodevelopmental disorders, highlighting the need for sex-specific human risk assessment in environmental toxicology. Full article

Post-traumatic stress symptoms (PTSSs) are associated with an imbalanced time perspective (TP) as well as with unhealthy substance use. Although neurodevelopmental processes during adolescence may impact PTSS, most etiological models of post-traumatic stress disorder (PTSD) are derived from studies with adults and neglect possible distinctive characteristics in adolescent PTSD. This study examined possible direct and mediated relations between exposure to potentially traumatic experiences (EPTEs) and PTSS with TP as a potential mediator. In addition, the study investigated the direct and indirect effects of EPTE, TP, and PTSS on cannabis use. The aim of this study was to investigate whether findings from adult studies can be transferred to adolescent PTSD. One hundred and five patients between 14 and 20 years of age were recruited from child and adolescent psychiatric units. They answered questionnaires to assess EPTE, PTSS, TP, and cannabis use. Participants with clinically relevant PTSS showed imbalanced TP with a high orientation to negative past and a low orientation to positive past and future. Higher EPTE was associated with higher level of PTSS, but TP mediated the level of PTSS in this relation. PTSS predicted the frequency of cannabis use. It may therefore be beneficial to consider TP in PTSD therapy with the aim of reducing deviation from balanced TP and PTSS and preventing comorbid substance use. Full article

Individuals with severe mental illness face a substantially higher risk of suicide compared with the general population, with drug overdose representing one of the most common and potentially lethal methods. This narrative review explores toxidromes frequently encountered in psychiatric populations, such as opioid, anticholinergic, and serotonergic toxicity, highlighting the clinical presentation in intentional overdose. Emphasis is placed on clinical recognition, antidote-based treatment, and systems-level strategies for the prevention of lethal overdose. We conducted a comprehensive literature search of PubMed, Google Scholar, and Web of Science for English-language articles using combinations of the following keywords: mental disorders; persons with psychiatric disorders; drug overdose; poisoning; serotonin syndrome; neuroleptic malignant syndrome; anticholinergic agents/poisoning; cholinergic antagonists/poisoning; psychotropic drugs/adverse effects; substance-related disorders; drug-related side effects and adverse reactions; polypharmacy; suicide, attempted; emergency service, hospital. By embedding toxidrome awareness into routine emergency and psychiatric practice, we aim to expedite treatment and improve patient outcomes. Full article

Storage of Blood units determines the accumulation of harmful substances, such as malondialdehyde (MDA) and free hemoglobin (fHb). These may lead to several complications, including cardiovascular, neurodegenerative, and metabolic disorders in recipients. The objective of this study was to evaluate the concentrations of MDA and fHb in canine leukoreduced (LR) and non-leukoreduced (NLR) packed red blood cells (pRBC) during the storage period of six weeks. Blood samples were collected from six healthy adult Weimaraner dogs (three females and three males). Whole blood was stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol additive solution (CPD-SAGM) bags and, for each donor, two pRBC units (one NLR and one LR) were produced and stored at 4 °C for 42 days. Samples were collected on days 0, 7, 14, 21, 28, 35, and 42, and analyzed for malondialdehyde (MDA) using a canine-specific ELISA method, and for free hemoglobin (fHb) using the Harboe direct spectrophotometric method. The results demonstrated a statistically significant reduction in MDA accumulation in LR-pRBC compared to NLR-pRBC blood units and lower values of fHb in LR at T6. However, no significant difference in fHb levels were demonstrated. These findings suggest that leukoreduction may limit oxidative stress during blood storage, reducing the potential adverse effects of transfusions related to oxidative damage. Full article

MRGPRX2 (Mas-related G protein-coupled receptor member X2) is implicated in mast cell (MC)-driven disorders due to its ability to bind diverse ligands, which may be G-protein-biased or balanced, with the latter activating both G-proteins and the β-arrestin pathway. Icatibant, a peptide drug, produces injection-site reactions in most patients and is used experimentally to probe MRGPRX2 function in skin tests. While reported to be G-protein-biased, it is unknown how skin MCs respond to icatibant, although these are the primary target cells during therapy. We therefore compared responses to icatibant with those induced by the balanced agonist substance P (SP) in skin MCs. Degranulation and desensitization were assessed via β-hexosaminidase release, receptor internalization by flow cytometry, and downstream signaling by immunoblotting. Skin MCs degranulated in response to SP and icatibant, relying on Gi proteins and calcium channels; Gq and PI3K (Phosphoinositide 3-kinase) contributed more strongly to exocytosis following icatibant, while JNK (c-Jun n-terminal kinase) was more relevant for SP. Both agonists activated ERK, PI3K/AKT, and (weakly) p38. Surprisingly, and in contrast to the LAD2 (Laboratory of Allergic Diseases 2 mast cell line) MC line, icatibant was at least as potent as SP in eliciting MRGPRX2 internalization and (cross-)desensitization in skin MCs. These findings suggest that icatibant functions differently in primary versus transformed MCs, acting as a fully balanced ligand in the former by triggering not only degranulation but also receptor internalization and desensitization. Therefore, not only the ligand but also the MRGPRX2-expressing cell plays a decisive role in whether a ligand is balanced or biased. These findings are relevant to our understanding of icatibant’s clinical effects on edema and itch. Full article

This study aimed to map the literature on the clinical role of pharmacists in the care of incarcerated people at correctional facilities and to identify gaps in this field. A scoping review was conducted on 30 July 2024, using the PubMed, Scopus, and LILACS databases. Gray literature was searched via Google Scholar, and references of included studies were manually reviewed. Primary studies of any design reporting pharmacists’ clinical services and/or activities for incarcerated individuals were eligible. Study selection and data extraction were performed independently by two reviewers, with a third resolving disagreements. The search yielded 894 records, from which 27 studies were included. Most studies were conducted in the United States (n = 16; 59%) and France (n = 7; 26%). Eleven (41%) focused exclusively on male populations, and one (4%) on female inmates. Most studies addressed pharmacists’ clinical roles in mental health conditions and substance use disorders (n = 9; 33%), infectious diseases (n = 5; 19%), and diabetes (n = 4; 15%). Clinical services and/or activities related to direct patient care were the most frequently reported (n = 18; 67%). Process measures were reported in 18 studies (67%), and clinical outcomes were the most common type of outcome (n = 13; 48%). This review highlights the pharmacist’s clinical role in treating mental health conditions and substance abuse, infectious diseases, and diabetes in incarcerated care. It underscores the need for further research in low- and middle-income countries, on women’s health, and on other prevalent conditions. Full article

Background/Objectives: Recent data shows increasing diabetes prevalence among African Americans. Youth with a family history of diabetes are at high risk for diabetes. This study explores the multilevel risk factors associated with a family history of diabetes among African American youth in public housing. Methods: This study used a cross-sectional, quantitative, and community-based participatory research (CBPR) approach. The research team, comprising community stakeholders and academic researchers, employed respondent-driven sampling (RDS) for data collection (survey) and used univariate and bivariate analyses to examine variable relationships. A sequential logistic regression highlighted factors influencing the likelihood of having a family history of diabetes. Results: The final sample (n = 190, mean age 18.5 years, 58% female) included 35% of youth with a family history of diabetes. Forty-six percent reported medium to severe household hardships. Results suggest that reporting a family history of diabetes is correlated with maternal substance use (tau-b = 0.27 **) and alcohol problems (tau-b = 0.16 ***), paternal substance use (tau-b = 0.17 *), and eating fewer fruits (tau-b = 0.17 *). With an odds ratio (OR) of 1.70 [0.68, 4.13] and attributable fraction among the exposed at 41.3%, the final model (3) was not significant [χ² = 11.19(8)]. Thus, we fail to reject the null hypothesis that the model fits the data well. Fewer vegetable consumption (OR = 15.08, p < 0.001), higher soda consumption (OR = 0.06, p < 0.001), severe household hardships (OR = 5.82, p < 0.01), and maternal substance use problems (OR = 6.81, p < 0.05) predicted a higher likelihood of a history of diabetes. Conclusions: Our study calls attention to the need to reevaluate interventions for hardships and substance use in diabetes management, particularly in poor neighborhoods and among minority families. Full article

Background/Objectives: Parents of individuals with substance use disorders (SUDs) often carry significant emotional and relational burdens, yet their voices remain underrepresented in addiction research. This study explores how Greek parents navigate the long-term challenges of caring for adult children with SUDs, with a focus on emotional strain, caregiving identity, and culturally embedded coping strategies within a collectivist context. Methods: Eight Greek parents (six mothers and two fathers, aged 47–60) participated in in-depth, semi-structured interviews. Conversations were conducted either in person or via video call, depending on participant preference and geographical constraints. Data were analyzed using Interpretative Phenomenological Analysis (IPA) to explore lived experience and the meaning-making processes shaping parental coping over time. Results: Four overarching themes were identified as follows: (1) Living in Vigilance, reflecting constant hyper-alertness, emotional exhaustion, and social withdrawal rooted in trauma; (2) Shifting Parental Identity, capturing the evolution of parents into caregivers, advocates, and informal caseworkers amid systemic neglect; (3) Struggling Within Systems, highlighting exclusion, blame, and fragmentation in institutional care—with moments of empathy holding outsized emotional weight; and (4) Coping as Cultural Duty, showing how caregiving was sustained through values of sacrifice, loyalty, and protective silence, even at great personal cost. Conclusions: Greek parents supporting adult children with SUDs face a complex interplay of trauma, cultural obligation, and institutional strain. Their coping is shaped by deeply held familial values rather than access to effective support. The findings call for culturally attuned, family-inclusive interventions and further research into long-term caregiving across diverse contexts. Full article

The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing enzymes, transporters, inflammatory factors, lipid metabolism, and immune-related pathways, contributing to the maintenance of hepatic–intestinal barrier homeostasis, energy metabolism, and inflammatory responses. Specifically, in type 2 diabetes mellitus (T2DM), PXR influences disease progression by regulating glucose metabolism and insulin sensitivity. In obesity, it affects adipogenesis and inflammatory processes. In atherosclerosis (AS), PXR exerts protective effects through cholesterol metabolism and anti-inflammatory actions. In metabolic dysfunction-associated steatotic liver disease (MASLD), it is closely associated with lipid synthesis, oxidative stress, and gut microbiota balance. Moreover, PXR plays dual roles in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Currently, PXR-targeted strategies, such as small molecule agonists and antagonists, represent promising therapeutic avenues for treating metabolic diseases and cancer. This review comprehensively summarizes the structural features, signaling pathways, and gene regulatory functions of PXR, as well as its role in metabolic diseases and cancer, providing insights into its therapeutic potential and future drug development challenges. Full article

Substance use disorders (SUDs) remain a major public health challenge, with existing pharmacotherapies offering limited long-term efficacy. Traditional treatments focus on dopaminergic systems but often overlook the complex interplay between metabolic signals, neuroplasticity, and conditioned behaviors that perpetuate addiction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have recently emerged as promising modulators of reward-related brain circuits. This review synthesizes current evidence on the role of glucagon-like peptide-1 (GLP-1) and its receptor in modulating craving and substance-seeking behaviors. We highlight how GLP-1 receptors are expressed in addiction-relevant brain regions, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC), where their activation influences dopaminergic, glutamatergic, and GABAergic neurotransmission. In addition, we explore how GLP-1 signaling affects reward processing through gut–brain vagal pathways, hormonal crosstalk, and neuroinflammatory mechanisms. Preclinical studies demonstrate that GLP-1RAs attenuate intake and relapse-like behavior across a range of substances, including alcohol, nicotine, and cocaine. Early-phase clinical trials support their safety and suggest potential efficacy in reducing craving. By integrating findings from molecular signaling, neurocircuitry, and behavioral models, this review provides a translational perspective on GLP-1RAs as an emerging treatment strategy in addiction medicine. We propose that targeting gut–brain metabolic signaling could provide a novel framework for understanding and treating SUDs. Full article

Maternal health has a profound impact on fetal development, influencing the risk of pediatric endocrine disorders both directly and indirectly through various biological and environmental mechanisms. Throughout pregnancy, several endocrine disorders can arise or be exacerbated due to the physiological changes that occur. An in-depth review of articles with evidence-based research discussing the significant effects of maternal endocrinopathies and endocrine disruptors on fetal development and infant health was conducted in this review paper. The most common endocrine disorder during pregnancy is gestational diabetes mellitus, which has an incidence rate of 2–16%, depending on ethnic origin. Maternal diabetes, apart from macrosomia and hypoglycemia, increases the risk for several pregnancy and neonatal complications such as stillbirth, perinatal mortality, and congenital malformations. Other endocrine issues occurring in pregnancy include alterations in thyroid hormone levels, obesity-related insulin resistance, Cushing syndrome, or polycystic ovarian syndrome, which all may negatively influence the fetus, as well as offspring development. Additionally, environmental exposure to harmful substances during pregnancy can disrupt endocrine function. Bisphenol A is the most common endocrine disruptor, which is particularly detrimental during gestation. Bisphenol A exposure is related to low birth weight, preterm birth, or developmental delays. Also, its exposition could be associated with an increased risk of obesity, metabolic disorders, and certain cancers later in life. Endocrinopathies and exposure to endocrine disruptors during pregnancy represent a challenging problem, being widespread and demanding appropriate management to reduce fetal and newborn complications. Full article

Background: Schizophrenia is a serious mental health condition that usually begins in adolescence and often progresses to become a chronic and disabling illness. Difficulties in communication and anomalous language are considered core elements of the disorder. Several studies have demonstrated the presence of semantic deficits in individuals with schizophrenia, suggesting that these deficits may constitute a core feature of the disorder. However, research in this area remains limited, particularly among individuals at high risk of developing the disorder. The central hypothesis of this study is that individuals with schizophrenia exhibit semantic processing deficits, even when cognitive function, psychopathology, and medication are controlled for. We also hypothesize that similar, albeit milder, deficits can be observed in individuals at high risk of developing the condition. Methods: This cross-sectional study included 155 participants divided into three groups: 46 with schizophrenia, 42 at high risk due to factors like substance use and high psychopathology, and 67 controls matched by sex, age, and education. Semantic processing was assessed using the semantic relations subtest from the BETA, controlling for medication and cognitive performance as possible confounding factors. Results: the results revealed significant differences among the three groups (F = 28.543; p < 0.001); the schizophrenia group performed poorly, followed by the high-risk group, and then the control group, which showed no deficits. Error patterns were also analyzed to assess group differences, revealing that the schizophrenia group had the lowest scores and the most specific deficits. These findings highlight the relevance of semantic evaluation in schizophrenia and, more importantly, in individuals at high risk of developing the disorder, as such deficits may serve as early biomarkers. Additionally, significant correlations were found between semantic performance and variables such as medication (r = −0.342; p = 0.020), cognition (r = −0.259; p = 0.001), and psychopathology (r = −0.566; p < 0.001). Conclusions: This emphasizes the need to control these factors to avoid misinterpreting semantic deficits in both schizophrenia and high-risk groups. The present research is not without limitations; for example, the study design does not allow for conclusions of causality but rather of correlation. Full article

Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use. Full article

The use of opioids for cancer-related pain is essential but poses significant challenges due to the risk of misuse and the development of opioid use disorder (OUD). This review takes a multidisciplinary perspective based on the current scientific literature to analyze the pharmacological mechanisms, classification, and therapeutic roles of opioids in oncology. Key risk factors for opioid misuse—including psychiatric comorbidities, prior substance use, and insufficient clinical monitoring—are discussed in conjunction with validated tools for pain assessment and international guidelines. The review emphasizes the importance of integrating toxicological, pharmacological, physiological, and public health perspectives to promote rational opioid use. Pharmacogenetic variability is explored as a determinant of treatment response and addiction risk, underscoring the value of personalized medicine. Evidence-based strategies such as early screening, psychosocial interventions, and the use of buprenorphine-naloxone are presented as effective measures for managing OUD in cancer patients. Ultimately, this work advocates for safe, patient-centered opioid prescribing practices that ensure effective pain relief without compromising safety or quality of life. Full article