Search Results (2,735)

Low prolactin levels in men predispose them to mood disturbances, sexual dysfunction, and diabetes. The purpose of the current study was to assess cardiometabolic risk in males with hypoprolactinemia. This prospective study included three age-matched groups of young and middle-aged men: individuals with cabergoline-induced hypoprolactinemia (n = 15), cabergoline-treated subjects with prolactin levels within the reference range (n = 20), and untreated men with normal prolactin levels (n = 31). In men with hypoprolactinemia, the cabergoline dose was reduced in order to normalize prolactin concentration. Anthropometric parameters, blood pressure, QRISK3 score; plasma concentrations of prolactin, glucose, insulin, lipids, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and testosterone; whole-blood levels of glycated hemoglobin (HbA_1C); urinary albumin-to-creatinine ratio (UACR); and carotid intima–media thickness were assessed at baseline and six months later. Men with hypoprolactinemia were characterized by higher body mass index, fat content, waist circumference, systolic blood pressure, fasting and 2 h post-load glucose, HbA_1C, HOMA1-IR, uric acid, hsCRP, fibrinogen, homocysteine, and UACR; by lower HDL cholesterol and testosterone; by greater intima–media thickness; and by a higher QRISK3 score than their peers with normal prolactin levels. There were no statistically significant differences in the measured parameters between both groups of men with normal prolactin levels. Normalization of prolactin concentration was accompanied by normalization of biochemical variables, systolic blood pressure, and QRISK3 score. Although cabergoline dose reduction did not cause statistically significant changes in the remaining anthropometric parameters and intima–media thickness, six months later, they did not differ from those observed in the remaining study groups. Our findings suggest that iatrogenic hypoprolactinemia is associated with increased cardiometabolic risk, which is reversible and resolves after the normalization of prolactin levels. Full article

We describe the design, synthesis and structure–activity relationship of a novel series of 1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with combined effects on the serotonin (5-HT_1A) and dopamine (D₂) receptors and the serotonin (5-HT), noradrenaline (NA), and dopamine (DA) transporters as multi-target directed ligands for the treatment of depression. All of the tested compounds demonstrated good affinity for the serotonin transporter (SERT). Among them, compounds 11 and 4 emerged as the lead candidates because of their promising pharmacological profile based on in vitro studies. Compound 11 displayed a high affinity for the 5-HT_1A (K_i = 128.0 nM) and D₂ (K_i = 51.0 nM) receptors, and the SERT (K_i = 9.2 nM) and DAT (K_i = 288.0 nM) transporters, whereas compound 4 exhibited the most desirable binding profile to SERT/NET/DAT among the series: K_i = 47.0 nM/167.0 nM/43% inhibition at 1 µM. These results suggest that compounds 4 and 11 represent templates for the future development of multi-target antidepressant drugs. Full article

Mixed matrix lithium adsorbents have attracted much interest for lithium recovery from brine. However, the absence of an interfacial interaction between the inorganic lithium-ion sieves (LISs) and the organic polymer matrix resulted in the poor structural stability and attenuated lithium adsorption efficiency. Here, a novel hollow hemispherical mixed matrix lithium adsorbent (H-LIS) with high interfacial compatibility was constructed based on mussel-bioinspired surface chemistry using a solvent evaporation induced phase transition method. The effects of types of functional modifiers, LIS loading amount, adsorption temperature and pH on their structural stability and lithium adsorption performance were systematically investigated. The optimized H-LIS adsorbent with the LIS loading amount of 50 wt.% possessed the structural merit that the LIS functionally modified by dopamine exposed on both the inner and outer surfaces of the hollow hemispheres. At the best adsorption pH of 12.0, it showed a comparable lithium adsorption capacity of 25.68 mg·g⁻¹ to the powdery LIS within 4 h, favorable adsorption selectivity of Mg/Li and good reusability that could maintain over 90% of lithium adsorption capacity after the LiCl adsorption—0.25 M HCl pickling-DI water cleaning cycling processes for three times. The interfacial interaction mechanism of H-LIS for lithium adsorption was innovatively explored via advanced microcalorimetry technology. It suggested the nature of the Li⁺ adsorption process was exothermic and dopamine modification could reduce the activation energy for lithium adsorption from 15.68 kJ·mol⁻¹ to 13.83 kJ·mol⁻¹ and trigger a faster response to Li⁺ by strengthening the Li⁺-H⁺ exchange rate, which established the thermodynamic relationship between the structure and Li⁺ adsorption performance of H-LIS. This work will provide a technical support for the structural regulation of functional materials for lithium extraction from brine. Full article

The worm Caenorhabditis elegans, with its short lifecycle and well-known genetic and metabolic pathways, stands as an exemplary model organism for biological research. Its simplicity and genetic tractability make it an ideal system for investigating the effects of different conditions on its metabolism. The chemical analysis of this nematode was performed to identify specific metabolites produced by the worms when fed with either self- or nonself-DNA. A standard diet with OP50 feeding was used as a control. Different development stages were sampled, and their chemical composition was assessed by liquid chromatography–mass spectrometry combined with chemometrics, including both principal component analysis and orthogonal partial least squares discriminant analysis tools. The obtained data demonstrated that self-DNA-treated larvae, when arrested in their cycle, showed significant decreases in dynorphin, an appetite regulator of the nematode, and in N-formyl glycine, a known longevity promoter in C. elegans. Moreover, a substantial decrease was also recorded in the self-DNA-fed adults for the FMRF amide neuropeptide, an embryogenesis regulator, and for a dopamine derivative modulating nematode locomotion. In conclusion, this study allowed for the identification of key metabolites affected by the self-DNA diet, providing interesting hints on the main molecular pathways involved in its biological inhibitory effects. Full article

Parkinson’s disease (PD) is a progressive age-related neurodegenerative disorder affecting millions of people worldwide. Essentially, it is characterised by selective degeneration of dopamine neurons of the nigro-striatal pathway and intraneuronal aggregation of misfolded α-synuclein with formation of Lewy bodies and Lewy neurites. Moreover, specific small molecules of intermediary metabolism may have a definite pathophysiological role in PD. These include dopamine, levodopa, reduced glutathione, glutathione disulfide/oxidised glutathione, and the micronutrients thiamine and ß-Hydroxybutyrate. Recent research indicates that these small molecules can interact with α-synuclein and regulate its folding and potential aggregation. In this review, we discuss the current knowledge on interactions between α-synuclein and both the small molecules of intermediary metabolism in the brain relevant to PD, and many other natural and synthetic small molecules that regulate α-synuclein aggregation. Additionally, we analyse some of the relevant molecular mechanisms potentially involved. A better understanding of these interactions may have relevance for the development of rational future therapies. In particular, our observations suggest that the micronutrients ß-Hydroxybutyrate and thiamine might have a synergistic therapeutic role in halting or reversing the progression of PD and other neuronal α-synuclein disorders. Full article

The lanthanide series elements are transition metals used as critical components of electronics, as well as rechargeable batteries, fertilizers, antimicrobials, contrast agents for medical imaging, and diesel fuel additives. With the surge in their utilization, lanthanide metals are being found more in our environment. However, little is known about the health effects associated with lanthanide exposure. Epidemiological studies as well as studies performed in rodents exposed to lanthanum (La) suggest neurological damage, learning and memory impairment, and disruption of neurotransmitter signaling, particularly in serotonin and dopamine pathways. Unfortunately, little is known about the neurological effects of heavier lanthanides. As dysfunctions of serotonergic and dopaminergic signaling are implicated in multiple neurological conditions, including Parkinson’s disease, depression, generalized anxiety disorder, and post-traumatic stress disorder, it is of utmost importance to determine the effects of La and other lanthanides on these neurotransmitter systems. We therefore hypothesized that early-life exposure of light [La (III) or cerium (Ce (III))] or heavy [erbium (Er (III)) or ytterbium (Yb (III))] lanthanides in Caenorhabditis elegans could cause dysregulation of serotonergic and dopaminergic signaling upon adulthood. Serotonergic signaling was assessed by measuring pharyngeal pump rate, crawl-to-swim transition, as well as egg-laying behaviors. Dopaminergic signaling was assessed by measuring locomotor rate and egg-laying and swim-to-crawl transition behaviors. Treatment with La (III), Ce (III), Er (III), or Yb (III) caused deficits in serotonergic or dopaminergic signaling in all assays, suggesting both the heavy and light lanthanides disrupt these neurotransmitter systems. Concomitant with dysregulation of neurotransmission, all four lanthanides increased reactive oxygen species (ROS) generation and decreased glutathione and ATP levels. This suggests increased oxidative stress, which is a known modifier of neurotransmission. Altogether, our data suggest that both heavy and light lanthanide series elements disrupt serotonergic and dopaminergic signaling and may affect the development or pharmacological management of related neurological conditions. Full article

The gut microbiota, recognised for its vital functions in host health, operates as an endocrine organ, exerting systemic effects beyond the gastrointestinal tract. This “virtual organ” produces hormones that influence distal organs, including the brain. With its diverse microbial composition, the gut microbiota surpasses the biochemical complexity of traditional endocrine organs, generating neurotransmitters like GABA, dopamine, and serotonin. Despite challenges in culturing gut bacteria, advances in research methodologies have elucidated their role in behaviour, metabolism, appetite, and insulin resistance. As microbial endocrinology continues to evolve, further exploration of the intricate connections between hormones and the microbiome are anticipated, highlighting hormones’ pivotal role in the dynamic host–microbiota relationship. Full article

Fertilizers that release nutrients slowly can provide crops with consistent nutrients, while soils with good water-holding capacity can alleviate the impact of droughts on crops. Sodium alginate/carboxymethyl starch sodium/polydopamine/urea (SCPU) is a new kind of slow-release fertilizer with water absorption property. In this study, the Box–Behnken response surface methodology (RSM) was used to reveal the effects of concentrations of sodium alginate, carboxymethyl starch sodium, urea, calcium chloride and dopamine on the encapsulation efficiency and water absorption of SCPU. The results show that the optimum preparation conditions to obtain the highest level of encapsulation efficiency (89.27%) and water absorption (167.05%) are 2.2% sodium alginate, 5% carboxymethyl starch sodium, 30% urea, 1.9% calcium chloride and 0.52% dopamine. Full article

The synthesis and characterization of iron oxide nanostructures, specifically snowflake architecture, are investigated for their potential applications in electrochemical sensing systems. A Raman spectroscopy analysis reveals phase diversity in the synthesized powders. The pH of the synthesis affects the formation of the hematite (α-Fe₂O₃) and goethite (α-FeOOH). Scanning electron microscopy (SEM) images confirm the distinct morphologies of the particles, which are selectively obtained through recrystallization during the elongated reaction time. An electrochemical analysis demonstrates the differing behaviors of the particles, with synthesis pH affecting the electrochemical activity and surface area differently for each shape. Cyclic voltammetry measurements reveal reversible dopamine detection processes, with snowflake iron oxide showing lower detection limits than a mixture of snowflakes and cube-like particles. This research contributes to understanding the relationship between iron oxide nanomaterials’ structural, morphological, and electrochemical properties. It offers practical insights into their potential applications in sensor technology, particularly dopamine detection, with implications for biomedical and environmental monitoring. Full article

Background and Objectives: Parkinson’s disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT–1/PPAR–gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD. Full article

Inflammation is a tightly regulated process involving immune receptor recognition, immune cell migration, inflammatory mediator secretion, and pathogen elimination, all essential for combating infection and restoring damaged tissue. However, excessive inflammatory responses drive various human diseases. The autonomic nervous system (ANS) is known to regulate inflammatory responses; however, the detailed mechanisms underlying this regulation remain incompletely understood. Herein, we aimed to study the anti-inflammatory effects and mechanism of action of the ANS in RAW264.7 cells. Quantitative PCR and immunoblotting assays were used to assess lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) expression. The anti-inflammatory effects of catecholamines (adrenaline, noradrenaline, and dopamine) and acetylcholine were examined in LPS-treated cells to identify the receptors involved. Catecholamines inhibited LPS-induced TNFα expression by activating the β2 adrenergic receptor (β2-AR). β2-AR activation in turn downregulated the expression of Toll-like receptor 4 (TLR4) by stimulating protein kinase A (PKA) phosphorylation, resulting in the suppression of TNFα levels. Collectively, our findings reveal a novel mechanism underlying the inhibitory effect of catecholamines on LPS-induced inflammatory responses, whereby β2-AR activation and PKA phosphorylation downregulate TLR4 expression in macrophages. These findings could provide valuable insights for the treatment of inflammatory diseases and anti-inflammatory drug development. Full article

Alzheimer’s disease is a neurodegenerative condition primarily attributed to environmental factors, abnormal protein deposits, immune system dysregulation, and the consequential death of nerve cells in the brain. On the other hand, Parkinson’s disease manifests as a neurological disorder featuring primary motor, secondary motor, and non-motor symptoms, accompanied by the rapid demise of cells in the brain’s dopamine-producing region. Utilizing brain images for accurate diagnosis and treatment is integral to addressing both conditions. This study harnessed the power of artificial intelligence for classification processes, employing state-of-the-art transformer models such as Swin transformer, vision transformer (ViT), and bidirectional encoder representation from image transformers (BEiT). The investigation utilized an open-source dataset comprising 450 images, evenly distributed among healthy, Alzheimer’s, and Parkinson’s classes. The dataset was meticulously divided, with 80% allocated to the training set (390 images) and 20% to the validation set (90 images). Impressively, the classification accuracy surpassed 80%, showcasing the efficacy of transformer-based models in disease detection. Looking ahead, this study recommends delving into hybrid and ensemble models and leveraging the strengths of multiple transformer-based deep learning architectures. Beyond contributing crucial insights at the intersection of artificial intelligence and neurology, this research emphasizes the transformative potential of advanced models for enhancing diagnostic precision and treatment strategies in Alzheimer’s and Parkinson’s diseases. It signifies a significant step towards integrating cutting-edge technology into mainstream medical practices for improved patient outcomes. Full article

Multifunctional hydrogel dressings remain highly sought after for the promotion of skin wound regeneration. In the present study, multifunctional CHS-DA/HACC (CH) hydrogels with an interpenetrated network were constructed using hydroxypropyl trimethyl ammonium chloride modified chitosan (HACC) and dopamine-modified chondroitin sulfate (CHS-DA), using genipin as crosslinker. The synthesis of HACC and CHS-DA was effectively confirmed using Fourier transform infrared (FT-IR) analysis and ¹H nuclear magnetic resonance (¹H NMR) spectroscopy. The prepared CH hydrogels exhibited a network of interconnected pores within the microstructure. Furthermore, rheological testing demonstrated that CH hydrogels exhibited strong mechanical properties, stability, and injectability. Further characterization investigations showed that the CH hydrogels showed favorable self-healing and self-adhesion properties. It was also shown that increasing HACC concentration ratio was positively correlated with the antibacterial activity of CH hydrogels, as evidenced by their resistance to Escherichia coli and Staphylococcus aureus. Additionally, Cell Counting Kit-8 (CCK-8) tests, fluorescent images, and a cell scratch assay demonstrated that CH hydrogels had good biocompatibility and cell migration ability. The multifunctional interpenetrated network hydrogels were shown to have good antibacterial properties, antioxidant properties, stable storage modulus and loss modulus, injectable properties, self-healing properties, and biocompatibility, highlighting their potential as wound dressings in wound healing applications. Full article

There is a gap in existing knowledge of stress-triggered neurochemical and behavioral adaptations in females. This study was designed to explore the short-term consequences of a single social defeat (SD) on accumbal dopamine (DA) dynamics and related behaviors in female Wistar rats. During the SD procedure, rats demonstrated different stress-handling strategies, which were defined as active and passive coping. The “active” subjects expressed a significantly higher level of activity directed toward handling stress experience, while the “passive” ones showed an escalated freezing pattern. Remarkably, these opposite behavioral manifestations were negatively correlated. Twenty-four hours following the SD exposure, decreased immobility latency in the Porsolt test and cognitive augmentation in the new object recognition evaluation were evident, along with an increase in electrically evoked mesolimbic DA release in passive coping rats. Rats exhibiting an active pattern of responses showed insignificant changes in immobility and cognitive performance as well as in evoked mesolimbic DA response. Furthermore, the dynamics of the decline and recovery of DA efflux under the depletion protocol were significantly altered in the passive but not active female rats. Taken together, these data suggest that female rats with a passive coping strategy are more susceptible to developing behavioral and neurochemical alterations within 24 h after stress exposure. This observation may represent both maladaptive and protective responses of an organism on a short timescale. Full article

The phenolic composition of virgin olive oil (VOO) primarily depends on the phenolic content of the olive fruit. The purpose of this work was to characterize the first metabolic step in the synthesis of tyrosol (Ty) and hydroxytyrosol (HTy), whose derivatives are by far the predominant phenolics in both olive fruit and VOO. To this end, two genes encoding tyrosine/DOPA decarboxylase enzymes, OeTDC1 and OeTDC2, have been identified and functionally and physiologically characterized. Both olive TDC proteins exclusively accept aromatic amino acids with phenolic side chains, such as tyrosine and 3,4-dihydroxyphenylalanine (DOPA), as substrates to produce tyramine and dopamine, respectively. These proteins exhibited a higher affinity for DOPA than for tyrosine, and the catalytic efficiency of both proteins was greater when DOPA was used as a substrate. Both olive TDC genes showed a fairly similar expression profile during olive fruit ontogeny, with OeTDC1 consistently expressed at higher levels than OeTDC2. Expression was particularly intense during the first few weeks after fruit set, coinciding with the active accumulation of Ty and HTy derivatives. The data suggest that both olive TDCs are responsible for the initial step in the synthesis of the most important phenolics, both quantitatively and functionally, in VOO. Full article