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Particulate matter (PM) is a major component of ambient air pollution. PM exposure is linked to numerous adverse health effects, including chronic lung diseases. Air quality guidelines designed to regulate levels of ambient PM are currently based on the mass concentration of different particle sizes, independent of their origin and chemical composition. The objective of this study was to assess the relative hazardous effects of carbonaceous particles (soot), ammonium nitrate, ammonium sulfate, and copper oxide (CuO), which are standard components of ambient air, reflecting contributions from primary combustion, secondary inorganic constituents, and non-exhaust emissions (NEE) from vehicular traffic. Human epithelial cells representing bronchial (BEAS-2B) and alveolar locations (H441 and A549) in the airways, human lung fibroblasts (HFL-1), and rat precision-cut lung slices (PCLS) were exposed in submerged cultures to different concentrations of particles for 5–72 h. Following exposure, cell viability, metabolic activity, reactive oxygen species (ROS) formation, and inflammatory responses were analyzed. CuO and, to a lesser extent, soot reduced cell viability in a dose-dependent manner, increased ROS formation, and induced inflammatory responses. Ammonium nitrate and ammonium sulfate did not elicit any significant cytotoxic responses but induced immunomodulatory alterations at very high concentrations. Our findings demonstrate that secondary inorganic components of PM have a lower hazard cytotoxicity compared with combustion-derived and indicative NEE components, and alveolar epithelial cells are more sensitive to PM exposure. This information should help to inform which sources of PM to target and feed into improved, targeted air quality guidelines. [ABSTRACT FROM AUTHOR]

Proteasome-mediated protein degradation is essential for maintaining cellular homeostasis, particularly during spermatogenesis, where extensive cellular transformations, such as spermatid differentiation, require precise protein turnover. A key player in this process is the ubiquitin–proteasome system (UPS). This study aimed to investigate proteasome enzymatic activity at different stages of the spermatogenic cycle within the seminiferous tubules of mice and explore the regulatory mechanisms that influence its proteolytic function. Specifically, we assessed the trypsin-like, chymotrypsin-like, and peptidyl-glutamyl-peptide-hydrolyzing (PGPH) activities of the proteasome. Additionally, we examined the expression of catalytic and structural subunits of the 20S core, the assembly of the 20S core with regulatory complexes, and the phosphorylation status of proteasome subunits in various segments of the seminiferous tubules. Our findings demonstrated distinct patterns of proteasomal enzymatic activity in the analyzed segments. While the expression levels of structural and catalytic subunits of the 20S core remained consistent, significant differences were detected in the assembly of the 20S core, the expression of regulatory complexes, and the phosphorylation of proteasome subunits mediated by protein kinase A. These results indicate that proteasomal activity is finely regulated through multiple mechanisms depending on the specific stage of the seminiferous epithelial cycle, highlighting the complexity of proteostasis during spermatogenesis. [ABSTRACT FROM AUTHOR]

Electroretinograms (ERGs) show differences between typically developing populations and those with a diagnosis of autism spectrum disorder (ASD) or attention deficit/hyperactivity disorder (ADHD). In a series of ERGs collected in ASD (n = 77), ADHD (n = 43), ASD + ADHD (n = 21), and control (n = 137) groups, this analysis explores the use of machine learning and feature selection techniques to improve the classification between these clinically defined groups. Standard time domain and signal analysis features were evaluated in different machine learning models. For ASD classification, a balanced accuracy (BA) of 0.87 was achieved for male participants. For ADHD, a BA of 0.84 was achieved for female participants. When a three-group model (ASD, ADHD, and control) the BA was lower, at 0.70, and fell further to 0.53 when all groups were included (ASD, ADHD, ASD + ADHD, and control). The findings support a role for the ERG in establishing a broad two-group classification of ASD or ADHD, but the model's performance depends upon sex and is limited when multiple classes are included in machine learning modeling. [ABSTRACT FROM AUTHOR]

Farnesoid X receptor (FXR), a nuclear receptor, is expressed in calvaria and bone marrow stromal cells and plays a role in bone homeostasis. However, the mechanism of FXR-activated osteoblast differentiation remains unclear. In this study, we investigated the regulatory mechanism underlying FXR-activated osteoblast differentiation using bone morphogenetic protein-2 (BMP-2)-induced mouse ST-2 mesenchymal stem cells. We also synthesized a novel FXR agonist, FLG390, and compared its biological effects in osteoblast differentiation with a known FXR agonist, chenodeoxycholic acid (CDCA). As an FXR agonist, FLG390 accelerated osteoblast differentiation to a comparable extent with CDCA, enhancing alkaline phosphatase (ALP) activity and the expression of osteoblast differentiated-related genes such as ALP, collagen type 1 α1 chain (COL1A1), and runt-related transcription factor 2 (RUNX2). FXR activation elevated the expression of cyclooxygenase (COX)-2 and the production of prostaglandin (PG) E2 in the early phase of osteoblast differentiation. A selective COX-2 inhibitor and an antagonist of EP4 receptors, one of PGE2 receptors, partially suppressed FXR-activated osteoblast differentiation. Moreover, treatment with either inhibitor during the first 6 h after initiating osteoblast differentiation repressed FXR-activated osteoblast differentiation to the same extent as did the treatment for 6 d. Therefore, a novel FXR agonist, FLG390, exhibited potency comparable to CDCA. FXR activation promoted the early phase of osteoblast differentiation via the COX-2-PGE2-EP4 axis, representing a potential target for control of bone metabolism. [ABSTRACT FROM AUTHOR]

The substantial evidence supporting the ketogenic diet (KD) in epilepsy management has spurred research into its effects on other neurological and psychiatric conditions. Despite differences in characteristics, symptoms, and underlying mechanisms, these conditions share common pathways that the KD may influence. The KD reverses metabolic dysfunction. Moreover, it has been shown to support neuroprotection through mechanisms such as neuronal energy support, inflammation reduction, amelioration of oxidative stress, and reversing mitochondrial dysfunction. The adequate intake of dietary nutrients is essential for maintaining normal brain functions, and strong evidence supports the role of nutrition in the treatment and prevention of many psychiatric and neurological disorders. Obsessive–compulsive disorder (OCD) is a neuropsychiatric condition marked by persistent, distressing thoughts or impulses (obsessions) and repetitive behaviors performed in response to these obsessions (compulsions). Recent studies have increasingly examined the role of nutrition and metabolic disorders in OCD. This narrative review examines current evidence on the potential role of the KD in the treatment of OCD. We explore research on the KD's effects on psychiatric disorders to assess its potential relevance for OCD treatment. Additionally, we identify key gaps in the preclinical and clinical research that warrant further study in applying the KD as a metabolic therapy for OCD. [ABSTRACT FROM AUTHOR]

The escalating issue of air pollution contributes to an alarming number of premature fatalities each year, thereby posing a significant threat to global health. The focus of recent research has shifted towards understanding its potential association with neurodegenerative diseases, specifically Alzheimer's disease (AD). AD is recognised for its characteristic deposition of toxic proteins within the brain, leading to a steady deterioration of cognitive capabilities, memory failure, and, ultimately, death. There is burgeoning evidence implying that air pollution may be a contributing factor to this protein build up, thereby intensifying the course of AD. It has been demonstrated that the olfactory system, responsible for smell perception and processing, acts as a potential gateway for airborne pollutants to inflict brain damage. This review aims to elucidate the relationship between air pollution, olfactory deterioration, and AD. Additionally, this review aims to highlight the potential mechanisms through which pollutants might instigate the development of AD and the role of the olfactory system in disease pathogenesis. Moreover, the diverse model systems employed in exploring the correlation, public health policy ramifications, and prospective directions for future research will be discussed. [ABSTRACT FROM AUTHOR]

The rising prevalence of depression, with its associated suicide risk, demands effective fast-acting treatments. Ketamine has emerged as promising, demonstrating rapid antidepressant effects. While early studies show swift mood improvements, its precise mechanisms remain unclear. This article aims to compile and synthesize the literature on ketamine's molecular actions. Ketamine primarily works by antagonizing NMDA receptors, reducing GABAergic inhibition, and increasing glutamate release. This enhanced glutamate activates AMPA receptors, triggering crucial downstream cascades, including BDNF-TrkB and mTOR pathways, promoting synaptic proliferation and regeneration. Moreover, neuroimaging studies have demonstrated alterations in brain networks involved in emotional regulation, including the Default Mode Network (DMN), Central Executive Network (CEN), and Salience Network (SN), which are frequently disrupted in depression. Despite the promising findings, the literature reveals significant inaccuracies and gaps in understanding the full scope of ketamine's therapeutic potential. For instance, ketamine engages with opioid receptors, insinuating a permissive role of the opioid system in amplifying ketamine's antidepressant effects, albeit ketamine does not operate as a direct opioid agonist. Further exploration is requisite to comprehensively ascertain its safety profile, long-term efficacy, and the impact of genetic determinants, such as BDNF polymorphisms, on treatment responsiveness. [ABSTRACT FROM AUTHOR]

Psychoactive drugs are compounds that alter the function of the central nervous system, resulting in changes in perception, mood, cognition, and behavior. A subclass of psychoactive drugs, psychedelics, are hallucinogenic drugs that can trigger psychedelic experiences and possible changes in mental perception. The potential use of psychedelics as a therapeutic has led to an increase in clinical research focusing on the treatment of mental disorders including anxiety and depression. There are numerous species belonging to Psychotria and Banisteriopsis which have been reported to contain psychedelic and psychoactive compounds; however, there is a lack of validated analytical methods for raw plant material, which is crucial if these plants are to be commercially cultivated for medicines. This study provides a fully validated method using ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry (MS) for the following six compounds: tryptamine, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), tetrahydroharmine (THH), harmaline, and harmine. The validated method was used to determine the psychoactive concentrations in Psychotria viridis, Psychotria carthagenensis, Banisteriopsis caapi, and Alicia anisopetala. Validation parameters were established; linearity (R2 = 0.988–0.999), limit of detection (LOD) (0.06–0.11 ng/mL), limit of quantitation (LOQ) (0.18–0.34 ng/mL), accuracy, precision, extraction efficiency (>98%), recovery (74.1–111.6%), and matrix effect (70.6–109%) were all evaluated. All six compounds eluted within nine minutes, with a total analysis time of 20 min including column equilibration. This method establishes a high-throughput method for the robust analysis of psychedelics which may see future use in agricultural research and industry. [ABSTRACT FROM AUTHOR]

The olive oil supply chain generates a substantial number of by-products, presenting significant environmental, economic, and social challenges. However, these by-products, such as pomace, wastewater, and biomass, also offer valuable opportunities for implementing a circular economy (CE) model that enhances sustainability. Despite increasing attention to the valorization of these by-products, understanding of the indicators used to measure circularity in this context remains limited. This systematic review examined the existing literature on circular economy indicators employed to assess the use of by-products in the olive oil supply chain. The aim was to provide a comprehensive overview of the most suitable indicators in this sector, while identifying best practices for quantifying and monitoring progress towards a more circular system. The review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and bibliometric analysis was conducted using CiteSpace 6.4 R1 software. The results highlighted a key indicator, the Material Circularity Indicator (MCI). Additionally, methodologies such as Life Cycle Assessment (LCA) and water footprint (WF) were evaluated, while challenges were identified, including the need for standardized metrics and improved data collection across the supply chain. This review provides valuable insights for both future research and policy decisions aimed at promoting sustainability and circularity in the olive oil industry. [ABSTRACT FROM AUTHOR]

The effects of air quality on health and cognition are well documented, but few studies have focused on its impact on emotions, leaving this area underexplored. This study investigates the influence of environmental factors—specifically particulate matter (PM1, PM2.5, and PM10) and carbon dioxide (CO2)—on students' basic emotions in secondary school classrooms. For the collection of environmental data, we used low-cost sensors, which were carefully calibrated to ensure acceptable accuracy for monitoring air quality variables, despite inherent precision limitations compared to traditional sensors. Emotions were recorded via camera and analyzed using a custom-developed code. Based on these data, we found significant but modest correlations, such as the negative correlation between PM levels and happiness, and positive correlations of CO2 concentrations with fear and disgust. The regression models explained between 36% and 62% of the variance in emotions like neutrality, sadness, fear, and happiness, highlighting nonlinear relationships in some cases. These findings underscore the need for improved classroom environmental management, including the implementation of real-time air quality monitoring systems. Such systems would enable schools to mitigate the negative emotional effects of poor air quality, contributing to healthier and more conducive learning environments. Future research should explore the combined effects of multiple environmental factors to further understand their impact on student well-being. [ABSTRACT FROM AUTHOR]

Uncompetitive NMDAR (N-methyl-D-aspartate receptor) antagonists restore impaired neural plasticity, reverse depressive-like behavior in animal models, and relieve major depressive disorder (MDD) in humans. This review integrates recent findings from in silico, in vitro, in vivo, and human studies of uncompetitive NMDAR antagonists into the extensive body of knowledge on NMDARs and neural plasticity. Uncompetitive NMDAR antagonists are activity-dependent channel blockers that preferentially target hyperactive GluN2D subtypes because these subtypes are most sensitive to activation by low concentrations of extracellular glutamate and are more likely activated by certain pathological agonists and allosteric modulators. Hyperactivity of GluN2D subtypes in specific neural circuits may underlie the pathophysiology of MDD. We hypothesize that neural plasticity is epigenetically regulated by precise Ca2+ quanta entering cells via NMDARs. Stimuli reach receptor cells (specialized cells that detect specific types of stimuli and convert them into electrical signals) and change their membrane potential, regulating glutamate release in the synaptic cleft. Free glutamate binds ionotropic glutamatergic receptors regulating NMDAR-mediated Ca2+ influx. Quanta of Ca2+ via NMDARs activate enzymatic pathways, epigenetically regulating synaptic protein homeostasis and synaptic receptor expression; thereby, Ca2+ quanta via NMDARs control the balance between long-term potentiation and long-term depression. This NMDAR Ca2+ quantal hypothesis for the epigenetic code of neural plasticity integrates recent psychopharmacology findings into established physiological and pathological mechanisms of brain function. [ABSTRACT FROM AUTHOR]

Brain connectivity represents the functional organization of the brain, which is an important indicator for evaluating neuropsychiatric disorders and treatment effects. Schizophrenia is associated with impaired functional connectivity but characterizing the complex abnormality patterns has been challenging. In this work, we used resting-state functional magnetic resonance imaging (fMRI) data to measure functional connectivity between 55 schizophrenia patients and 63 healthy controls across 246 regions of interest (ROIs) and extracted the disease-related connectivity patterns using energy landscape (EL) analysis. EL analysis captures the complexity of brain function in schizophrenia by focusing on functional brain state stability and region-specific dynamics. Age, sex, and smoker demographics between patients and controls were not significantly different. However, significant patient and control differences were found for the brief psychiatric rating scale (BPRS), auditory perceptual trait and state (APTS), visual perceptual trait and state (VPTS), working memory score, and processing speed score. We found that the brains of individuals with schizophrenia have abnormal energy landscape patterns between the right and left rostral lingual gyrus, and between the left lateral and orbital area in 12/47 regions. The results demonstrate the potential of the proposed imaging analysis workflow to identify potential connectivity biomarkers by indexing specific clinical features in schizophrenia patients. [ABSTRACT FROM AUTHOR]

Many children suffer from neurodevelopmental aberrations that have long-term effects. To understand the consequences of pathological processes during particular periods in neurodevelopment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate during development but one of the last to achieve maturity. This relatively long period of development underscores its vulnerability to detrimental environmental exposures throughout gestation. Moreover, as postnatal functionality of the cerebellum is multifaceted, enveloping sensorimotor, cognitive, and emotional domains, prenatal disruptions in cerebellar development can result in a large variety of neurological and mental health disorders. Here, we review major intrauterine insults that affect cerebellar development in both humans and rodents, ranging from abuse of toxic chemical agents, such as alcohol, nicotine, cannabis, and opioids, to stress, malnutrition, and infections. Understanding these pathological mechanisms in the context of the different stages of cerebellar development in humans and rodents can help us to identify critical and vulnerable periods and thereby prevent the risk of associated prenatal and early postnatal damage that can lead to lifelong neurological and cognitive disabilities. The aim of the review is to raise awareness and to provide information for obstetricians and other healthcare professionals to eventually design strategies for preventing or rescuing related neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

The Topo River basin, located in the tropical region of Ecuador, is considered a little-known and well-preserved basin, with limited access conditions and scarce data that hinder its hydrological understanding. However, this gap can be addressed through this study, which evaluates morphometric and hydrometeorological factors, relating them to water storage in the Topo River basin and comparing these results with other watersheds. The aim is to identify the morphometric and hydrometeorological factors that control the variability in water storage. Firstly, a morphometric characterization was conducted. Then, a hydrometeorological characterization was carried out based on climatic data from a single station with less than two years of data, along with the calculation of the water balance. Finally, water storage in the Topo basin was compared with the main morphometric and hydrometeorological characteristics of other basins. The results showed that the Topo River basin stores 9.1 mm annually (0.20% of its precipitation), and this storage is the result of its high runoff coefficient. It was concluded that basins with lower precipitation, higher evapotranspiration ranges, larger areas, gentler slopes, smaller altitude ranges, longer rivers, and basins that are narrow and oval-shaped may have higher water storage capacity. [ABSTRACT FROM AUTHOR]

Simple Summary: With global warming, heat stress has become an increasingly serious problem for poultry because of their abundant feathers, limited sweat glands, and fast metabolism. To alleviate the losses caused by poultry heat stress, it is important to investigate the mechanisms and control strategies for poultry heat stress. When heat stress occurs, the neuroendocrine system in poultry will be disrupted, while several organs in the body will be damaged, affecting the poultry's production performance and health. Adding nutrients to feed is a mild and effective means of heat stress management and holds significant implications for the poultry farming industry. Heat stress (HS) due to high temperatures has adverse effects on poultry, including decreased feed intake, lower feed efficiency, decreased body weight, and higher mortality. There are complex mechanisms behind heat stress in poultry involving the neuroendocrine system, organ damage, and other physiological systems. HS activates endocrine glands, such as the pituitary, adrenal, thyroid, and gonadal, by the action of the hypothalamus and sympathetic nerves, ultimately causing changes in hormone levels: HS leads to increased corticosterone levels, changes in triiodothyronine and thyroxine levels, decreased gonadotropin levels, reduced ovarian function, and the promotion of catecholamine release, which ultimately affects the normal productive performance of poultry. Meanwhile, heat stress also causes damage to the liver, lungs, intestines, and various immune organs, severely impairing organ function in poultry. Nutrient additives to feed are important measures of prevention and treatment, including natural plants and extracts, probiotics, amino acids, and other nutrients, which are effective in alleviating heat stress in poultry. Future studies need to explore the specific mechanisms through which heat stress impacts the neuroendocrine system in poultry and the interrelationships between the axes and organ damage so as to provide an effective theoretical basis for the development of preventive and treatment measures. [ABSTRACT FROM AUTHOR]

Inflammation has been recognized as major factor for successful bone regeneration. On the other hand, a prolonged or overshooting inflammatory response can also cause fracture healing failure. The nucleotide-binding oligomerization domain (NOD)-like receptor protein (NLRP)3 inflammasome plays a crucial role in inflammatory cytokine production. However, its role during fracture repair remains elusive. We investigated the effects of Nlrp3 deficiency on the healing of closed femoral fractures in Nlrp3−/− and wildtype mice. The callus tissue was analyzed by means of X-ray, biomechanics, µCT and histology, as well as immunohistochemistry and Western blotting at 2 and 5 weeks after surgery. We found a significantly reduced trabecular thickness at 2 weeks after fracture in the Nlrp3−/− mice when compared to the wildtype animals. However, the amount of bone tissue did not differ between the two groups. Additional immunohistochemical analyses showed a reduced number of CD68-positive macrophages within the callus tissue of the Nlrp3−/− mice at 2 weeks after fracture, whereas the number of myeloperoxidase (MPO)-positive granulocytes was increased. Moreover, we detected a significantly lower expression of vascular endothelial growth factor (VEGF) and a reduced number of microvessels in the Nlrp3−/− mice. The expression of the absent in melanoma (AIM)2 inflammasome was increased more than 2-fold in the Nlrp3−/− mice, whereas the expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 was not affected. Our results demonstrate that Nlrp3 deficiency does not markedly affect femoral fracture healing in mice. This is most likely due to the unaltered expression of pro-inflammatory cytokines and pro-osteogenic growth factors. [ABSTRACT FROM AUTHOR]

Water in the engine/combustion chamber is not a novel phenomenon. Even humidity has a major effect on internal combustion engine emissions and can thus be considered the first invisibly present emission technology. With modern techniques, the problematic aspects of water, such as corrosion and lubrication issues, seem to disappear, and the benefits of water's effect in combustion may also be enhanced in the context of EURO 7. The current study examines the literature on the effects of water on diesel combustion in chronological sequence, focusing on changes over the last three decades. Then it analyzes and re-evaluates the water effect in the current technology and the forthcoming Euro 7 regulatory context, comparing the conclusions with current automotive applications and mobility trends, in order to show the possible benefits and prospective research avenues in this sector. Techniques introducing water to combustion could be a major approach in terms of the EURO 7 retrofit mandate, as well as a feasible technique for concurrent nitrogen oxides and particulate reduction. [ABSTRACT FROM AUTHOR]

Environmental pollution continues to increase with industrial development and has become a threat to human health. Atmospheric particulate matter (PM) was designated as a Group 1 carcinogen by the International Agency for Research on Cancer in 2013 and is an emerging global environmental risk factor that is a major cause of death related to cardiovascular and respiratory diseases. PM is a complex composed of highly reactive organic matter, chemicals, and metal components, which mainly cause excessive production of reactive oxygen species (ROS) that can lead to DNA and cell damage, endoplasmic reticulum stress, inflammatory responses, atherosclerosis, and airway remodeling, contributing to an increased susceptibility to and the exacerbation of various diseases and infections. PM has various effects on human health depending on the particle size, physical and chemical characteristics, source, and exposure period. PM smaller than 5 μm can penetrate and accumulate in the alveoli and circulatory system, causing harmful effects on the respiratory system, cardiovascular system, skin, and brain. In this review, we describe the relationship and mechanism of ROS-mediated cell damage, oxidative stress, and inflammatory responses caused by PM and the health effects on major organs, as well as comprehensively discuss the harmfulness of PM. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a hereditary disorder characterized by bones that are fragile and prone to breaking. The efficacy of existing therapies for OI is limited, and they are associated with potentially harmful side effects. OI is primarily due to a mutation of collagen type I and hence impairs bone regeneration. Mesenchymal stem cell (MSC) therapy is an attractive strategy to take advantage of the potential benefits of these multipotent stem cells to address the underlying molecular defects of OI by differentiating osteoblasts, paracrine effects, or immunomodulation. The maintenance of mitochondrial homeostasis is an essential component for improving the curative efficacy of MSCs in OI by affecting the differentiation, signaling, and immunomodulatory functions of MSCs. In this review, we highlight the MSC-based therapy pathway in OI and introduce the MSC regulation mechanism by mitochondrial homeostasis. Strategies aiming to modulate the metabolism and reduce the oxidative stress, as well as innovative strategies based on the use of compounds (resveratrol, NAD+, α-KG), antioxidants, and nanomaterials, are analyzed. These findings may enable the development of new strategies for the treatment of OI, ultimately resulting in improved patient outcomes. [ABSTRACT FROM AUTHOR]

Substance use/abuse and suicide are two closely related phenomena, mostly due to neurobiological, psychological, and social impairments. In the present narrative review, the relationship between suicidal behavior (SB) and the use and abuse of common recreational drugs, such as alcohol, cannabis, cocaine, methamphetamine, heroin, nicotine, ketamine, psilocybin, MDMA, and LSD, has been explored. Furthermore, potential mechanisms linking the two have also been examined. According to current research, all substances appear to have a deleterious effect on SB except for ketamine and psilocybin, which could potentially confer a protective effect. Further studies are needed to understand the relationship between MDMA, LSD, and suicide. [ABSTRACT FROM AUTHOR]

The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food. [ABSTRACT FROM AUTHOR]

Osteoporosis is a chronic disease that affects millions of patients worldwide and is characterized by low bone mineral density (BMD) and increased risk of fractures. Notably, natural molecules can increase BMD and exert pro-osteogenic effects. Noteworthily, the nutraceutical BlastiMin Complex® (Mivell, Italy, European Patent Application EP4205733A1) can induce differentiation of human bone marrow mesenchymal stem cells (BM-MSCs) in osteoblasts and can exert in vitro pro-osteogenic and anti-inflammatory effects. Thus, the purpose of this study was to verify the effects of BlastiMin Complex® on bone turnover markers (BTMs) and BMD in patients with senile and postmenopausal osteopenia or osteoporosis. The efficacy of BlastiMin Complex® on BTMs in serum was evaluated through biochemical assays. BMD values were analyzed by dual-energy X-ray absorptiometry (DXA) and Radiofrequency Echographic Multi Spectrometry (R.E.M.S.) techniques, and the SNPs with a role in osteoporosis development were evaluated by PCR. Clinical data obtained after 12 months of treatment showed an increase in bone turnover index, a decrease in C-reactive protein levels, and a remarkable increase in P1NP levels, indicating the induction of osteoblast proliferation and activity in the cohort of 100% female patients recruited for the study. These findings show that the nutraceutical BlastiMin Complex® could be used as an adjuvant in combination with synthetic drugs for the treatment of osteoporosis pathology. [ABSTRACT FROM AUTHOR]

Schizophrenia is a frequently debilitating and complex mental disorder affecting approximately 1% of the global population, characterized by symptoms such as hallucinations, delusions, disorganized thoughts and behaviors, cognitive dysfunction, and negative symptoms. Traditional treatment has centered on postsynaptic dopamine antagonists, commonly known as antipsychotic drugs, which aim to alleviate symptoms and improve functioning and the quality of life. Despite the availability of these medications, significant challenges remain in schizophrenia therapeutics, including incomplete symptom relief, treatment resistance, and medication side effects. This opinion article explores advancements in schizophrenia treatment, emphasizing molecular mechanisms, novel drug targets, and innovative delivery methods. One promising approach is novel strategies that target neural networks and circuits rather than single neurotransmitters, acknowledging the complexity of brain region interconnections involved in schizophrenia. Another promising approach is the development of biased agonists, which selectively activate specific signaling pathways downstream of receptors, offering potential for more precise pharmacological interventions with fewer side effects. The concept of molecular polypharmacy, where a single drug targets multiple molecular pathways, is exemplified by KarXT, a novel drug combining xanomeline and trospium to address both psychosis and cognitive dysfunction. This approach represents a comprehensive strategy for schizophrenia treatment, potentially improving outcomes for patients. In conclusion, advancing the molecular understanding of schizophrenia and exploring innovative therapeutic strategies hold promise for addressing the unmet needs in schizophrenia treatment, aiming for more effective and tailored interventions. Future research should focus on these novel approaches to achieve better clinical outcomes and improve the functional level and quality of life for individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

The advent of the digital era has catalyzed transformative shifts in educational paradigms, seamlessly integrating sustainable education with innovative pedagogical approaches that cater to a broader spectrum of learners and educators. As the academic landscape evolves into an information-dense environment, traditional models of one-on-one feedback often fall short, resulting in delays and a lack of diverse intellectual engagement. This shift underscores the growing importance of peer feedback and asynchronous post-lesson feedback mechanisms, which have emerged as vital, process-oriented educational activities. Such mechanisms not only address the immediacy and diversity of feedback but also foster a sustainable, collaborative, and engaging learning environment that bolsters student autonomy and interaction. This study conducts a mapping review and synthesis of the literature on peer interaction, assessment, and participatory innovations in online and mobile learning within higher education, covering the period from 1993 to 2022. By employing topic modeling techniques to analyze a corpus of 485 articles, the literature was initially segmented into 19 distinct issues. These were subsequently consolidated into three major thematic models, thereby highlighting significant themes, research focal points, and prospective trends. This analytical process not only enriches the understanding of peer dynamics in digital learning settings but also integrates sustainable educational practices by promoting resource efficiency and inclusivity. The findings serve as a robust reference for future researchers aiming to explore the intersections of technology, peer interaction, and sustainability in educational settings. [ABSTRACT FROM AUTHOR]

Autistic spectrum disorder (ASD) is a neurodevelopmental disability characterised by the impairment of social interaction and communication ability. The alarming increase in its prevalence in children urged researchers to obtain a better understanding of the causes of this disease. Genetic factors are considered to be crucial, as ASD has a tendency to run in families. In recent years, with technological advances, the importance of structural variations (SVs) in ASD began to emerge. Most of these studies, however, focus on the Caucasian population. As a populated ethnicity, ASD shall be a significant health issue in China. This systematic review aims to summarise current case-control studies of SVs associated with ASD in the Chinese population. A list of genes identified in the nine included studies is provided. It also reveals that similar research focusing on other genetic backgrounds is demanded to manifest the disease etiology in different ethnic groups, and assist the development of accurate ethnic-oriented genetic diagnosis. [ABSTRACT FROM AUTHOR]

The Water Footprint (WF) is an indicator used to determine good practices for efficiently using water in human activities. This work evaluates the green (rainfed) and blue (irrigation) water footprint of avocado cultivation in the municipalities of Acuitzio (2012–2016) and Morelia (2016–2020) in Michoacán, Mexico. Likewise, the water stress of irrigation water use is analyzed, linking the blue WF with the volumes of concessions for agricultural use. The results revealed that the mean green WF for Acuitzio is 1292.49 m3/ton, and the mean blue WF is 689.23 m3/ton. In Morelia, the mean green WF is 582.97 m3/ton, and the mean blue WF is 711.74 m3/ton. The mean production of irrigated avocado in Acuitzio is 7963.62 (ton/year), and in Morelia, 8547.76 (ton/year), which allows us to project that, in Acuitzio, the avocado crop requires an annual mean of 5,046,610.69 m3, while the mean requirement in Morelia is 6,029,920.59 m3. The average volume of water for agricultural use in Acuitzio is 3,357,782.93 m3, while the average water demand is 149.27%. This situation shows water stress in this municipality since water consumption exceeds available water resources. For Morelia, the water available for agricultural use is 11,418,745.40 m3, and the average consumption of avocado as a crop is 53.18%, which can put the supply of this resource for other agricultural crops at risk. [ABSTRACT FROM AUTHOR]

NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). (S)-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of (R)-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than (S)-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of (R)-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with (R)-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications. [ABSTRACT FROM AUTHOR]

Investigating the biophysiological substrates of psychiatric illnesses is of great interest to our understanding of disorders' etiology, the identification of reliable biomarkers, and potential new therapeutic avenues. Schizophrenia represents a consolidated model of γ alterations arising from the aberrant activity of parvalbumin-positive GABAergic interneurons, whose dysfunction is associated with perineuronal net impairment and neuroinflammation. This model of pathogenesis is supported by molecular, cellular, and functional evidence. Proof for alterations of γ oscillations and their underlying mechanisms has also been reported in bipolar disorder and represents an emerging topic for major depressive disorder. Although evidence from animal models needs to be further elucidated in humans, the pathophysiology of γ-band alteration represents a common denominator for different neuropsychiatric disorders. The purpose of this narrative review is to outline a framework of converging results in psychiatric conditions characterized by γ abnormality, from neurochemical dysfunction to alterations in brain rhythms. [ABSTRACT FROM AUTHOR]

A healthy gut microbiome is crucial for the immune system and overall development of infants. Bifidobacterium has been known to be a predominant species in the infant gut; however, an emerging concern is the apparent loss of this genus, in particular, Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiome of infants in industrialized nations, underscoring the importance of restoring this beneficial bacterium. With the growing understanding of the gut microbiome, probiotics, especially infant-type human-residential bifidobacteria (HRB) strains like B. infantis, are gaining prominence for their unique ability to utilize HMOs and positively influence infant health. This article delves into the physiology of a probiotic strain, B. infantis M-63, its symbiotic relationship with HMOs, and its potential in improving gastrointestinal and allergic conditions in infants and children. Moreover, this article critically assesses the role of HMOs and the emerging trend of supplementing infant formulas with the prebiotic HMOs, which serve as fuel for beneficial gut bacteria, thereby emulating the protective effects of breastfeeding. The review highlights the potential of combining B. infantis M-63 with HMOs as a feasible strategy to improve health outcomes in infants and children, acknowledging the complexities and requirements for further research in this area. [ABSTRACT FROM AUTHOR]

Simple Summary: Psilocybin therapy shows promise for reducing anxiety and depression and improving psychological well-being in cancer patients nearing the end of life. However, providing this treatment outside of tightly controlled research studies is extremely challenging. In 2020, Oregon became the first U.S. state to legalize psilocybin therapy for depression related to terminal illnesses such as advanced cancer. This review examines the published evidence on psilocybin's therapeutic potential as well as the multitude of legal, ethical, and logistical hurdles Oregon has faced while attempting to roll out regulated psilocybin services over the past year. The aim is to shed light on the complex issues involved in responsibly implementing psychedelic-assisted therapy for patient populations with serious psychological distress. By proactively identifying and addressing these challenges, appropriate standards of care and equitable access to psilocybin treatment can be ensured as it transitions from research to real-world clinical practice. Insights from Oregon's experience as the pioneering state can help guide a rigorous, ethical path forward. Despite the legalization of psilocybin therapy for depression in terminal illnesses such as advanced cancer through Oregon's Measure 109 in 2020, significant challenges have impeded its implementation. This review synthesizes the empirical data supporting the utilization of psilocybin therapy for addressing cancer-related depression, including an evaluation of its purported benefits and potential adverse effects. It provides a comprehensive examination of therapeutic strategies, dosing regimens, and barriers to ensuring responsible and equitable access. Salient issues explored include the development of ethical protocols, integration within healthcare systems, ensuring statewide availability, resolving legal ambiguities, and defining clinical standards. Oregon's pioneering role serves as a case study, highlighting the necessity of addressing regulatory, logistical, and ethical obstacles to ensure the establishment of rigorous and equitable psilocybin care models. [ABSTRACT FROM AUTHOR]

The recent approval of formulations of the endogenous neurosteroid allopregnanolone (brexanolone) and the synthetic neuroactive steroid SAGE-217 (zuranolone) to treat postpartum depression (PPD) has encouraged further research to elucidate why these potent enhancers of GABAAR function are clinically effective in this condition. Dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens are associated with reward/motivation and brain imaging studies report that individuals with PPD show reduced activity of this pathway in response to reward and infant engagement. However, the influence of neurosteroids on GABA-ergic transmission in the nucleus accumbens has received limited attention. Here, we investigate, in the medium spiny neurons (MSNs) of the mouse nucleus accumbens core, the effect of allopregnanolone, SAGE-217 and other endogenous and synthetic steroids of interest on fast phasic and tonic inhibition mediated by synaptic (α1/2βγ2) and extrasynaptic (α4βδ) GABAARs, respectively. We present evidence suggesting the resident tonic current results from the spontaneous opening of δ-GABAARs, where the steroid-enhanced tonic current is GABA-dependent. Furthermore, we demonstrate local neurosteroid synthesis in the accumbal slice preparation and reveal that GABA-ergic neurotransmission of MSNs is influenced by an endogenous neurosteroid tone. Given the dramatic fluctuations in allopregnanolone levels during pregnancy and postpartum, this neurosteroid-mediated local fine-tuning of GABAergic transmission in the MSNs will probably be perturbed. [ABSTRACT FROM AUTHOR]

Antioxidant vanillin (4-hydroxy-3-methoxybenzaldehyde) is used as a flavoring in foods, beverages, and pharmaceuticals. Vanillin possesses various biological effects, such as antioxidant, anti-inflammatory, antibacterial, and anticancer properties. This study aimed to investigate the biological activities of vanillin purified from Adenophora triphylla var. japonica Hara on bone-forming processes. Vanillin treatment induced mineralization as a marker for mature osteoblasts, after stimulating alkaline phosphatase (ALP) staining and activity. The bone-forming processes of vanillin are mainly mediated by the upregulation of the bone morphogenetic protein 2 (BMP2), phospho-Smad1/5/8, and runt-related transcription factor 2 (RUNX2) pathway during the differentiation of osteogenic cells. Moreover, vanillin promoted osteoblast-mediated bone-forming phenotypes by inducing migration and F-actin polymerization. Furthermore, we validated that vanillin-mediated bone-forming processes were attenuated by noggin and DKK1. Finally, we demonstrated that vanillin-mediated antioxidant effects prevent the death of osteoblasts during bone-forming processes. Overall, vanillin has bone-forming properties through the BMP2-mediated biological mechanism, indicating it as a bone-protective compound for bone health and bone diseases such as periodontitis and osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) is a devastating autoimmune disease, and its rising prevalence in the United States and around the world presents a critical problem in public health. While some treatment options exist for patients already diagnosed, individuals considered at risk for developing T1D and who are still in the early stages of their disease pathogenesis without symptoms have no options for any preventive intervention. This is because of the uncertainty in determining their risk level and in predicting with high confidence who will progress, or not, to clinical diagnosis. Biomarkers that assess one's risk with high certainty could address this problem and will inform decisions on early intervention, especially in children where the burden of justifying treatment is high. Single omics approaches (e.g., genomics, proteomics, metabolomics, etc.) have been applied to identify T1D biomarkers based on specific disturbances in association with the disease. However, reliable early biomarkers of T1D have remained elusive to date. To overcome this, we previously showed that parallel multi-omics provides a more comprehensive picture of the disease-associated disturbances and facilitates the identification of candidate T1D biomarkers. Methods: This paper evaluated the use of machine learning (ML) using data augmentation and supervised ML methods for the purpose of improving the identification of salient patterns in the data and the ultimate extraction of novel biomarker candidates in integrated parallel multi-omics datasets from a limited number of samples. We also examined different stages of data integration (early, intermediate, and late) to assess at which stage supervised parametric models can learn under conditions of high dimensionality and variation in feature counts across different omics. In the late integration scheme, we employed a multi-view ensemble comprising individual parametric models trained over single omics to address the computational challenges posed by the high dimensionality and variation in feature counts across the different yet integrated multi-omics datasets. Results: the multi-view ensemble improves the prediction of case vs. control and finds the most success in flagging a larger consistent set of associated features when compared with chance models, which may eventually be used downstream in identifying a novel composite biomarker signature of T1D risk. Conclusions: the current work demonstrates the utility of supervised ML in exploring integrated parallel multi-omics data in the ongoing quest for early T1D biomarkers, reinforcing the hope for identifying novel composite biomarker signatures of T1D risk via ML and ultimately informing early treatment decisions in the face of the escalating global incidence of this debilitating disease. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and severe side effects. Recently, two categories of fast-acting antidepressant compounds have surfaced, dissociative anesthetics S-ketamine and its metabolites, as well as psychedelics such as lysergic acid diethylamide (LSD). This has led to structural research and drug development of the receptors that they target. This review provides breakthroughs and achievements in the structure of depression-related receptors and novel ADs based on these. Cryo-electron microscopy (cryo-EM) has enabled researchers to identify the structures of membrane receptors, including the N-methyl-D-aspartate receptor (NMDAR) and the 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution structures can be used for the development of novel ADs using virtual drug screening (VDS). Moreover, the unique antidepressant effects of 5-HT1A receptors in various brain regions, and the pivotal roles of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and tyrosine kinase receptor 2 (TrkB) in regulating synaptic plasticity, emphasize their potential as therapeutic targets. Using structural information, a series of highly selective ADs were designed based on the different role of receptors in MDD. These molecules have the favorable characteristics of rapid onset and low adverse drug reactions. This review offers researchers guidance and a methodological framework for the structure-based design of ADs. [ABSTRACT FROM AUTHOR]

Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine's use in treating adolescents' major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1–10, total score), and CDI (items A–E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). Most GABAergic neurons synthesize GABA from glutamate and release it in the synaptic cleft in the CNS. However, astrocytes can also synthesize and release GABA, activating GABA receptors in the neighboring neurons in physiological and pathological conditions. As the primary homeostatic glial cells in the brain, astrocytes play a crucial role in regulating GABA homeostasis and synaptic neurotransmission. Accumulating evidence demonstrates that astrocytic GABA dysregulation is implicated in psychiatric disorders, including alcohol use disorder (AUD) and major depressive disorder (MDD), the most prevalent co-occurring psychiatric disorders. Several current medications and emerging pharmacological agents targeting GABA levels are in clinical trials for treating AUD and MDD. This review offers a concise summary of the role of astrocytic GABA regulation in AUD and MDD. We also provide an overview of the current understanding and areas of debate regarding the mechanisms by which astrocytes regulate GABA in the CNS and their potential significance in the molecular basis of AUD and MDD, paving the way toward future research directions and potential therapeutic target areas within this field. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most lethal malignancies worldwide. Peroxisome proliferator-activated receptor gamma (PPARγ, NR1C3) is a ligand-activated transcriptional factor that governs the expression of genes involved in glucolipid metabolism, energy homeostasis, cell differentiation, and inflammation. Multiple studies have demonstrated that PPARγ activation exerts anti-tumor effects in lung cancer through regulation of lipid metabolism, induction of apoptosis, and cell cycle arrest, as well as inhibition of invasion and migration. Interestingly, PPARγ activation may have pro-tumor effects on cells of the tumor microenvironment, especially myeloid cells. Recent clinical data has substantiated the potential of PPARγ agonists as therapeutic agents for lung cancer. Additionally, PPARγ agonists also show synergistic effects with traditional chemotherapy and radiotherapy. However, the clinical application of PPARγ agonists remains limited due to the presence of adverse side effects. Thus, further research and clinical trials are necessary to comprehensively explore the actions of PPARγ in both tumor and stromal cells and to evaluate the in vivo toxicity. This review aims to consolidate the molecular mechanism of PPARγ modulators and to discuss their clinical prospects and challenges in tackling lung cancer. [ABSTRACT FROM AUTHOR]

The aim of this work is to study the effect of platelet factors on the differentiation of mesenchymal stem cells (MSCs) to hyaline cartilage chondrocytes in a three-dimensional environment. MSCs were cultured in a microgel environment with a chondrogenic medium. The microgel consisted of microspheres that combine gelatin and platelet-rich plasma (PRP). The gelatin/PRP microdroplets were produced by emulsion. The gelatin containing the microdroplets was enzymatically gelled, retaining PRP and, just before seeding the cells, platelets were activated by adding calcium chloride so that platelet growth factors were released into the culture media but not before. Platelet activation was analyzed before activation to rule out the possibility that the gelatin cross-linking process itself activated the platelets. The gene expression of characteristic chondrogenic markers and miRNA expression were analyzed in cells cultured in a differentiation medium and significant differences were found between gelation/PRP microgels and those containing only pure gelatin. In summary, the gelatin microspheres effectively encapsulated platelets that secreted and released factors that significantly contributed to cellular chondrogenic differentiation. At the same time, the microgel constituted a 3D medium that provided the cells with adherent surfaces and the possibility of three-dimensional cell–cell contact. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second leading cause of cancer death in men in the United States. Androgen deprivation therapy (ADT) is currently the primary treatment for metastatic prostate cancer, and some studies have shown that the use of anti-androgen drugs is related to a reduction in cognitive function, mood changes, diminished quality of life, dementia, and possibly Alzheimer's disease. ADT has potential physiological effects such as a reduction in white matter integrity and a negative impact on hypothalamic functions due to the lowering of testosterone levels or the blockade of downstream androgen receptor signaling by first- and second-generation anti-androgen drugs. A comparative analysis of prostate cancer patients undergoing ADT and Alzheimer patients identified over 30 shared genes, illustrating common ground for the mechanistic underpinning of the symptomatology. The purpose of this review was to investigate the effects of ADT on cognitive function, mood, and quality of life, as well as to analyze the relationship between ADT and Alzheimer's disease. The evaluation of prostate cancer patient cognitive ability via neurocognitive testing is described. Future studies should further explore the connection among cognitive deficits, mood disturbances, and the physiological changes that occur when hormonal balance is altered. [ABSTRACT FROM AUTHOR]

Fetus loss in early pregnancy is of major concern to both humans and animals, and this issue is largely influenced by embryo implantation. Chenodeoxycholic acid (CDCA), a primary bile acid, contributes to metabolic improvements and protects against intrahepatic cholestasis of pregnancy. However, the effect of CDCA on embryo implantation during early pregnancy has not been investigated. The present study demonstrated that CDCA administration during early pregnancy improved embryo implantation in sows and rats, thereby improving the pregnancy outcomes of sows. CDCA significantly reduced inflammation, oxidative stress, and insulin resistance. The metabolomics analysis indicated significant differences in the fecal metabolome, especially regarding the level of secondary bile acids, between the control and CDCA-treated sows. CDCA also influenced the serum metabolite profiles in sows, and the serum L-Histidine level was significantly correlated with the abundance of 19 differential fecal metabolites. Importantly, L-Histidine administration improved embryo implantation and metabolic health in rats during early pregnancy. Moreover, CDCA administration during early pregnancy also led to long-term metabolic improvements in sows. Our data indicated that CDCA improved embryo implantation by alleviating inflammation and oxidative stress, improving insulin sensitivity, and modulating the interaction between the gut microbiota and host metabolites. Therefore, CDCA intervention is a potential therapeutic strategy regarding embryo loss during pregnancy. [ABSTRACT FROM AUTHOR]

This document discusses the unique challenges in identifying biomarkers for psychotic disorders. Biomarkers are observations that provide information about the risk or underlying mechanisms of certain conditions. In the field of psychotic disorders, biomarker research is gaining momentum due to the preference for non-experiential signals in medicine and the assumption that biomarkers are located closer to molecular mechanisms. However, the search for optimal biomarkers in psychotic disorders has been challenging, and biomarkers that are decisive for clinical prediction have not yet been identified. There are significant knowledge gaps between different levels of analysis, and there is a need for biomarkers that are more proximal to key pathophysiological processes. The document also highlights the criteria for optimal biomarkers, which include being proximal to key processes, having well-defined links to higher- and lower-level components, being portable and low-burden, and having predictive capacity for the clinical course of the disorder. Overall, further research is needed to better understand and identify biomarkers for psychotic disorders. [Extracted from the article]

Bone tissue engineering is a promising solution for advanced bone defect reconstruction after severe trauma. In bone tissue engineering, scaffolds in three-dimensional (3D) structures are crucial components for cell growth, migration, and infiltration. The three-dimensional printing technique is well suited to manufacturing scaffolds since it can fabricate scaffolds with highly complex designs under good internal structural control. In the current study, the 3D printing technique was utilized to produce polylactic acid (PLA) scaffolds. BMSCs were seeded onto selected scaffolds, either hydrogel-mixed or not, and cultivated in vitro to investigate the osteogenic potential in each group. After osteogenic incubation in vitro, BMSC-seeded scaffolds were implanted onto rat cranium defects, and bone regeneration was observed after 12 weeks. Our results demonstrated that BMSCs were able to seed onto 3D-printed PLA scaffolds under high-resolution observation. Real-time PCR analysis showed their osteogenic ability, which could be further improved after BMSCs were mixed with hydrogel. The in vivo study showed significantly increased bone regeneration when rats' cranium defects were implanted with a hydrogel-mixed BMSC-seeded scaffold compared to the control and those without cell or hydrogel groups. This study showed that 3D-printed PLA scaffolds are a feasible option for BMSC cultivation and osteogenic differentiation. After mixing with hydrogel, BMSC-seeded 3D-printed scaffolds can facilitate bone regeneration. [ABSTRACT FROM AUTHOR]

PM2.5 exposure leads to a variety of respiratory diseases, including pulmonary fibrosis, metastatic lung cancer, etc. Exposure to PM2.5 results in the alteration of epigenetic modification. M6A RNA methylation is an essential epigenetic modification that regulates gene expression at the post-transcriptional level. Our previous study found that PM2.5 exposure up-regulated m6A RNA methylation and TGF-β expression level in the lung, but the mechanisms and pathways of PM2.5 regulation of m6A RNA methylation are still unclear. Moreover, a previous study reported that the TGF-β signal pathway could regulate m6A RNA methylation. Based on this evidence, we investigate the role of the TGF-β signaling pathway in PM2.5-induced m6A RNA methylation with the A549 cell line. Our results showed that PM2.5 could induce upregulation of m6A RNA methylation, accompanied by increased expression of TGF-β, Smad3, methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14). Furthermore, these alterations induced by PM2.5 exposure could be reversed by treatment with TGF-β inhibitor. Therefore, we speculated that the TGF-β signal pathway plays an indispensable role in regulating m6A RNA methylation after PM2.5 exposure. Our study demonstrates that PM2.5 exposure influences m6A RNA methylation by inducing the alteration of the TGF-β signal pathway, which could be an essential mechanism for lung-related diseases induced by PM2.5 exposure. [ABSTRACT FROM AUTHOR]

Definition: An operational stress injury (OSI) is a term used most often to describe mental disorders which result from, or are exacerbated by, military or police service. In the Canadian context, this most often refers to active or former members of the Canadian Armed Forces (CAF) or the Royal Canadian Mounted Police (RCMP). The most common diagnoses within this term include post-traumatic stress disorder (PTSD), anxiety disorders, depression, and substance use disorders. [ABSTRACT FROM AUTHOR]

Plant extracts are widely used as traditional medicines. Sophora flavescens Aiton-derived natural compounds exert various beneficial effects, such as anti-inflammatory, anticancer, antioxidant, and antiregenerative activities, through their bioactive compounds, including flavonoids and alkaloids. In the present study, we investigated the biological effects of an S. flavescens-derived flavonoid, trifolirhizin (trifol), on the stimulation of osteogenic processes during osteoblast differentiation. Trifol (>98% purity) was successfully isolated from the root of S. flavescens and characterized. Trifol did not exhibit cellular toxicity in osteogenic cells, but promoted alkaline phosphatase (ALP) staining and activity, with enhanced expression of the osteoblast differentiation markers, including Alp, ColI, and Bsp. Trifol induced nuclear runt-related transcription factor 2 (RUNX2) expression during the differentiation of osteogenic cells, and concomitantly stimulated the major osteogenic signaling proteins, including GSK3β, β-catenin, and Smad1/5/8. Among the mitogen-activated protein kinases (MAPKs), Trifol activated JNK, but not ERK1/2 and p38. Trifol also increased the osteoblast-mediated bone-forming phenotypes, including transmigration, F-actin polymerization, and mineral apposition, during osteoblast differentiation. Overall, trifol exhibits bioactive activities related to osteogenic processes via differentiation, migration, and mineralization. Collectively, these results suggest that trifol may serve as an effective phytomedicine for bone diseases such as osteoporosis. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF), the most common and severe of the idiopathic interstitial pneumonias, is a chronic and relentlessly progressive disease, which occurs mostly in middle-aged and elderly males. Although IPF is by definition "idiopathic", multiple factors have been reported to increase disease risk, aging being the most prominent one. Several occupational and environmental exposures, including metal dust, wood dust and air pollution, as well as various lifestyle variables, including smoking and diet, have also been associated with an increased risk of IPF, probably through interaction with genetic factors. Many of the predisposing factors appear to act also as trigger for acute exacerbations of the disease, which herald a poor prognosis. The more recent literature on inhalation injuries has focused on the first responders in the World Trade Center attacks and military exposure. In this review, we present an overview of the environmental and occupational causes of IPF and its pathogenesis. While our list is not comprehensive, we have selected specific exposures to highlight based on their overall disease burden. [ABSTRACT FROM AUTHOR]

This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations. [ABSTRACT FROM AUTHOR]

Background and Objectives: It is known that inflammatory processes play a role in the pathogenesis of autism spectrum disorder (ASD). It is also reported that immune activation induces the kynurenine pathway (KP), as known as the tryptophan destruction pathway. In our study, we aimed to investigate whether the serum levels of KP products and interleukin (IL)-6 activating indolamine 2–3 dioxygenase (IDO) enzyme are different in healthy developing children and children with ASD. Materials and Methods: Forty-three ASD children aged 2–9 were included in this study. Forty-two healthy developing children, similar to the patient group in terms of age and gender, were selected as the control group. Serum levels of kynurenic acid, kynurenine, quinolinic acid and IL-6 were analyzed using the ELISA method. ASD severity was evaluated with the Autism Behavior Checklist (ABC). Results: The mean age of children with ASD was 42.4 ± 20.5 months, and that of healthy controls was 48.1 ± 15.8 months. While the serum levels of kynurenic acid, kynurenine and interleukin-6 were higher in the group with ASD (p < 0.05), there was no significant difference (p > 0.05) in terms of the quinolinic acid level. There was no significant difference between the ABC total and subscale scores of children with ASD and biochemical parameters (p > 0.05). Conclusions: We conclude that these biomarkers must be measured in all ASD cases. They may be important for the diagnosis of ASD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a highly prevalent, debilitating disorder with a high rate of treatment resistance. One strategy to improve treatment outcomes is to identify patient-specific, pre-intervention factors that can predict treatment success. Neurophysiological measures such as electroencephalography (EEG), which measures the brain's electrical activity from sensors on the scalp, offer one promising approach for predicting treatment response for psychiatric illnesses, including MDD. In this study, a secondary data analysis was conducted on the publicly available Two Decades Brainclinics Research Archive for Insights in Neurophysiology (TDBRAIN) database. Logistic regression modeling was used to predict treatment response, defined as at least a 50% improvement on the Beck's Depression Inventory, in 119 MDD patients receiving repetitive transcranial magnetic stimulation (rTMS). The results show that both age and baseline symptom severity were significant predictors of rTMS treatment response, with older individuals and more severe depression scores associated with decreased odds of a positive treatment response. EEG measures contributed predictive power to these models; however, these improvements in outcome predictability only trended towards statistical significance. These findings provide confirmation of previous demographic and clinical predictors, while pointing to EEG metrics that may provide predictive information in future studies. [ABSTRACT FROM AUTHOR]

This study explores the potential of a natural composite formulation known as ED, consisting of Ecklonia cava (E. cava, family: Lessoniaceae) and Chrysanthemum indicum Linne (C. indicum, family: Asteraceae), in alleviating lung inflammation induced by fine particulate matter (PM2.5). Initial assessments confirmed that neither ED nor one of its components, dieckol, exhibited cytotoxic effects on A549 cells. Subsequently, the impact of ED and dieckol on MUC5AC gene expression in A549 cells stimulated by phorbol 12-myristate 13-acetate (PMA) was investigated, revealing promising results that demonstrated a dose-dependent inhibition of MUC5AC gene expression. The study also delves into the underlying mechanisms, demonstrating that ED and dieckol effectively suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including JNK, ERK, and p38, which are known to be involved in the regulation of MUC5AC gene expression. In in vivo experiments using a PM2.5-induced pulmonary inflammation mouse model, the research findings showed that ED mitigated cellular accumulation in the airways, leading to a significant reduction in the total cell count in bronchoalveolar lavage fluid (BALF). Moreover, ED exhibited protective effects against PM2.5-induced pulmonary damage, characterized by reduced inflammatory cell infiltration and decreased mucus secretion in pulmonary tissues. Additionally, ED's anti-inflammatory properties were evident in its ability to decrease the levels of key inflammatory cytokines, TNF-α and IL-6, both in the serum and lung tissue of the PM2.5-induced pulmonary inflammation mouse model. These findings suggest the potential of ED as a therapeutic agent for inflammatory respiratory diseases. [ABSTRACT FROM AUTHOR]