Search Results (94)

Pubertal molting represents a pivotal transition in the life cycle of crustaceans, marking the shift from somatic growth to reproductive development. In mud crabs, mating is known to facilitate this process, yet the molecular mechanisms remain poorly understood. Here, we applied full-length transcriptome sequencing to characterize changes in gene expression and alternative splicing (AS) across post-mating ovarian development. AS analysis revealed extensive transcript diversity, predominantly alternative first exon (AF) and alternative 5′ splice site (A5) events, enriched in genes linked to chromatin remodeling, protein regulation, and metabolism, underscoring AS as a fine-tuning mechanism in ovarian development. Comparative analyses revealed profound molecular reprogramming after mating. In the UM vs. M1 comparison, pathways related to serotonin and catecholamine signaling were enriched, suggesting early neuroendocrine regulation. Serotonin likely promoted, while dopamine inhibited, oocyte maturation, indicating a potential “inhibition–activation” switch. In the UM vs. M3 comparison, pathways associated with oxidative phosphorylation, ATP biosynthesis, and lipid metabolism were upregulated, reflecting heightened energy demands during vitellogenesis. ECM-receptor interaction, HIF-1, and IL-17 signaling pathways further pointed to structural remodeling and tissue regulation. Enhanced antioxidant defenses, including upregulation of SOD2, CAT, GPX4, and GSTO1, highlighted the importance of redox homeostasis. Together, these findings provide the first comprehensive view of transcriptional and splicing dynamics underlying post-mating ovarian maturation in Scylla paramamosain, offering novel insights into the molecular basis of crustacean reproduction. Full article

Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. While this underpins therapeutic efficacy, prolonged or abusive exposure has been associated with mitochondrial impairment, disrupted bioenergetics, and excessive reactive oxygen species (ROS) production, which collectively contribute to neuronal stress and long-term neurotoxicity. Growing evidence suggests that the gut–brain axis may critically influence MPH outcomes: diet-induced shifts in microbiome composition appear to regulate oxidative stress, neuroinflammation, and drug metabolism, opening potential avenues for dietary or probiotic interventions. From a forensic perspective, the detection and monitoring of MPH misuse require advanced methodologies, including enantioselective LC–MS/MS and analysis of alternative matrices such as hair or oral fluids, which enable retrospective exposure assessment and improves abuse surveillance. Despite its established therapeutic profile, MPH remains a compound with a narrow balance between clinical benefit and toxicological risk. Future directions should prioritize longitudinal human studies, biomarker identification for abuse monitoring, and the development of mitochondria-targeted therapies to minimize adverse outcomes and enhance safety in long-term treatment. Full article

Catecholamines (CA) are considered to play key roles in acute stress responses, but they also regulate important functions of the nervous, immune, and endocrine systems and are essential for body homeostasis and health. In Swiss mice (an outbred strain) with haploinsufficiency of the tyrosine hydroxylase gene (Th, TH-HZ), which encodes the rate-limiting enzyme of catecholamine synthesis, impairments in homeostatic system functions and a reduced lifespan have been reported. Moreover, these homeostatic alterations are exacerbated when these animals are exposed to acute restraint stress. Nonetheless, the effects of this genetic modification on an inbred strain, such as C57BL/6J, are undetermined. Given that the genetic background of mice can affect the phenotype of any genetic modification, this work aimed to characterize how behavioral responses, immunity, and the oxidative state in C57BL/6J mice are altered by Th haploinsufficiency under basal conditions after being subjected to 10 min of acute restraint stress. Sex differences were also considered. Compared with their WT counterparts, TH-HZ C57BL/6J animals exhibit behavioral impairments, immunosenescence, and oxidative stress under basal conditions. After stress, TH-HZ animals (both sexes) exhibit deteriorated behavior and immune functions. Therefore, Th haploinsufficiency in the inbred C57BL/6J strain triggers impairments in behavior, immunity, and the redox state. These findings corroborate the role of CA in maintaining regulatory system functions and highlight the importance of mouse strains in basic research. Full article

The gas transmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S) play important roles in physiological regulation, including adrenal function. Among them, only NO has been directly implicated in controlling catecholamine biosynthesis. This study examined whether CO and H₂S exert similar effects by treating PC12 cells with a CO donor (CORM-2) or an H₂S donor (NaHS), with or without glucocorticoid stimulation. Gene expression of tyrosine hydroxylase (Th), dopamine β-hydroxylase (Dbh), and phenylethanolamine N-methyltransferase (Pnmt) was assessed by RT-qPCR, and catecholamine release was measured by ELISA. We found that exogenous CO decreased Th and Dbh expression, attenuated glucocorticoid-induced upregulation of catecholamine biosynthesis genes, and differentially modulated dopamine and norepinephrine release. In contrast, exogenous H₂S treatment had no significant effect. These findings identify CO as a novel regulator of catecholamine biosynthesis and highlight important differences among gas transmitters in stress-related signaling. Full article

Mitochondrial dysfunction is a key contributor to neurodegeneration, particularly in Parkinson’s disease (PD), where dopaminergic neurons being highly metabolically active are vulnerable to oxidative stress and bioenergetic failure. In this study, we investigate the effects of rotenone, a Complex I inhibitor, and antimycin A, a Complex III inhibitor, on mitochondrial function in MN9D dopaminergic neuronal cells. Cells were treated with rotenone (1.5 µM) or antimycin A (10 µM) for one hour, and key biochemical parameters were assessed, including ATP levels, reactive oxygen species (ROS) production, dopamine metabolism, and neuromelanin formation. Our results indicate significant ATP depletion and ROS accumulation following treatment with both inhibitors, with antimycin A inducing a more pronounced oxidative stress response. Dysregulation of dopamine biosynthesis differed mechanistically from vesicular monoamine transporter (VMAT2) inhibition by tetrabenazine, suggesting alternative pathways of catecholamine disruption. Additionally, oxidative stress led to increased neuromelanin accumulation, indicating a possible adaptive response to mitochondrial dysfunction. These findings provide insights into the cellular mechanisms underlying dopaminergic neurotoxicity and highlight mitochondrial electron transport chain inhibition as a key driver of PD pathogenesis. Future research should explore therapeutic strategies aimed at enhancing mitochondrial function to mitigate neurodegenerative progression. Full article

Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic–pituitary–adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-α) within 1 day (p < 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p < 0.05), and oxidative damage (MDA levels doubled vs. CON; p < 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune–metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein–protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects. Full article

Dopamine is a major catecholamine neurotransmitter that plays an essential role in the functioning of the human central nervous system. Imbalances in dopamine levels are associated with neurological disorders and depression. Thus, measuring the concentration of DA in human body fluids is significantly important. In this work, TEMPO-oxidized cellulose nanofibrils (TOCNFs) extracted from marram grass (Ammophilia arenaria), harvested in the central western part of Tunisia, were utilized to modify disposable screen-printed carbon electrodes (SPCEs) for the sensitive detection of dopamine in biological fluids. Differential pulse voltammetry (DPV) measurements displayed a sensitivity of 7.92 µA/µM and a detection limit of 10 nM. The disposable TOCNF-modified SPCE presents a charge transfer coefficient, α, comparable to that of a TOCNF/graphene/AgNP composite-modified GCE. Moreover, it exhibits good repeatability (RSD = 1.9%), good reproducibility (RSD = 2.3%), and appreciable storage stability (91% of its initial response after 3 weeks). The prepared disposable sensor showed satisfactory recovery of dopamine in human urine samples. Full article

Neurodegenerative disorders are one of the main public health problems worldwide and, for this reason, they have attracted the attention of several researchers who aim to better understand the molecular processes linked to the etiology of these disorders, including Alzheimer’s and Parkinson’s diseases. In this review, we describe both the beneficial and toxic effect of norepinephrine (NE) and its connected ROS/metal-mediated pathways, which end in neuromelanin (NM) formation and protein aggregation. In particular, we emphasize the importance of stabilizing the delicate homeostatic balance that regulates (i) the metal/ROS-promoted oxidation of catecholamines, as NE, and (ii) the generation of oxidative by-products capable of covalently and non-covalently modifying neuroproteins, thus altering their stability and their oligomerization; these processes may end in (iii) the incorporation of protein conjugates into vesicles, which then evolve into neuromelanin (NM) organelles. In general, we aim to provide an up-to-date overview of the challenges and controversies emerging from the current literature to delineate a direction for future research. Full article

Khat, derived from the Catha edulis plant, is widely consumed in East Africa and the Arabian Peninsula, where it holds significant socio-cultural importance. This review examines the multifaceted effects of khat, particularly focusing on its cardiovascular implications. Khat’s active constituents, notably cathinone and cathine, exhibit stimulant and psychoactive properties akin to amphetamines, leading to heightened alertness and euphoria. However, chronic consumption is associated with adverse effects, including cardiovascular diseases such as hypertension, myocardial infarction, and cardiomyopathy. The review highlights the pharmacokinetics of khat, with cathinone being rapidly absorbed and leading to sympathomimetic effects. Studies indicate a correlation between chronic khat use and increased risks of hypertension, acute coronary syndromes, and cardiomyopathy. These cardiovascular conditions are exacerbated by prolonged hemodynamic stress, catecholamine release, and oxidative stress induced by khat’s active compounds. Additionally, khat’s impact extends beyond the cardiovascular system, affecting neurological, reproductive, and gastrointestinal health. Despite its legality in certain regions, khat is classified as a controlled substance in many countries, emphasizing the need for global awareness of its health risks. This review calls for longitudinal studies to elucidate the pathophysiological mechanisms of khat-induced cardiomyopathy and to identify potential biomarkers for its early detection. Furthermore, it advocates for culturally sensitive public health initiatives and clinical guidelines to mitigate the adverse health effects of khat consumption, especially among immigrant populations in developed nations. Recognizing and addressing khat’s cardiovascular implications is crucial for improving patient outcomes and guiding effective clinical practice. Full article

Vitamin C is an organic compound biosynthesized in plants and most vertebrates. Since its discovery, the benefits of vitamin C use in the cure and prevention of various pathologies have been frequently reported, including its anti-oxidant, anti-inflammatory, anticoagulant, and immune modulatory properties. Vitamin C plays an important role in collagen synthesis and subsequent scurvy prevention. It is also required in vivo as a cofactor for enzymes involved in carnitine and catecholamine norepinephrine biosynthesis, peptide amidation, and tyrosine catabolism. Moreover, as an enzymatic cofactor, vitamin C is involved in processes of gene transcription and epigenetic regulation. The absence of the synthesis of L-gulono-1,4-lactone oxidase, a key enzyme in the pathway of vitamin C synthesis, is an inborn metabolism error in some fishes and several bird and mammalian species, including humans and non-human primates; it is caused by various changes in the structure of the original GULO gene, making these affected species dependent on external sources of vitamin C. The evolutionary cause of GULO gene pseudogenization remains controversial, as either dietary supplementation or neutral selection is evoked. An evolutionary improvement in the control of redox homeostasis was also considered, as potentially toxic H₂O₂ is generated as a byproduct in the vitamin C biosynthesis pathway. The inactivation of the GULO gene and the subsequent reliance on dietary vitamin C may have broader implications for aging and age-related diseases, as one of the most important actions of vitamin C is as an anti-oxidant. Therefore, an important aim for medical professionals regarding human and animal health should be establishing vitamin C homeostasis in species that are unable to synthesize it themselves, preventing pathologies such as cardiovascular diseases, cognitive decline, and even cancer. Full article

Dopamine is a neurotransmitter which is classified as a catecholamine. It is also one of the main metabolites produced by some tumor types (such as paragangliomas and neoblastomas). As such, determining and monitoring the level of dopamine is of the utmost importance, ideally using analytical techniques that are sensitive, simple, and low in cost. Due to this, we have developed a non-enzymatic dopamine sensor that is highly sensitive, selective, and rapidly detects the presence of dopamine in the body. A hybrid material fabricated with NiO and ZnO, based on date fruit extract, was synthesized by hydrothermal methods and using NiO as a precursor material. This paper discusses the role of date fruit extracts in improving NiO’s catalytic performance with reference to ZnO and the role that they play in this process. An X-ray powder diffraction study, a scanning electron microscope study, and a Fourier transform infrared spectroscopy study were performed in order to investigate the structure of the samples. It was found that, in the composite NiO/ZnO, NiO exhibited a cubic phase and ZnO exhibited a hexagonal phase, both of which exhibited well-oriented aggregated cluster shapes in the composite. A hybrid material containing NiO and ZnO has been found to be highly electro-catalytically active in the advanced oxidation of dopamine in a phosphate buffer solution at a pH of 7.3. It has been found that this can be accomplished without the use of enzymes, and the range of oxidation used here was between 0.01 mM and 4 mM. The detection limit of non-enzymatic sensors is estimated to be 0.036 μM. Several properties of the non-enzymatic sensor presented here have been demonstrated, including its repeatability, selectivity, and reproducibility. A test was conducted on Sample 2 for the detection of banana peel and wheat grass, and the results were highly encouraging and indicated that biomass waste may be useful for the manufacture of medicines to treat chronic diseases. It is thought that date fruit extracts would prove to be valuable resources for the development of next-generation electrode materials for use in clinical settings, for energy conversion, and for energy storage. Full article

The aim of this study was to evaluate the combined effects of L-arginine, intermittent hypoxia training (IHT), and acute stress on oxygen-dependent processes in rats, including mitochondrial oxidative phosphorylation, microsomal oxidation, and the intensity of lipoperoxidation processes. In addition, our study investigated how the modulatory effect of the NO synthase mechanism on the concentration of catecholamines (CA), such as adrenaline and noradrenaline, and their biosynthetic precursors (DOPA, dopamine) varies depending on the cholinergic (acetylcholine, Ach-acetylcholinesterase, AChE) status in rats. This study investigated the protective stress-limiting effects of L-arginine impact and IHT in the blood and liver of rats. The results showed that L-arginine promoted the maintenance of NAD-dependent oxidation in mitochondria, which was detrimental compared to succinate oxidation, and was accompanied by depletion of respiratory activity reserves under stress induced by high concentrations of CA. The interdependence of SC-dependent oxidation and the functional role of NAD-dependent substrate oxidation in the mitochondrial respiratory chain in stress conditions induced using inhibitors revealed the importance of the NO system. Administration of L-arginine during the IHT course prior to stress exposure increased the compensatory capacity of the organism. L-arginine increased the compensatory capacity of the sympathoadrenal system in stress-exposed rats. In the early stages of IHT, modulation of the CA concentration was observed with a concomitant increase in lipoperoxidation processes, and in the final stages of IHT, the CA concentrations increased, but there was also an inhibition of lipoperoxidation, which was particularly enhanced by the administration of L-arginine. The increase in blood concentrations of CA and ACh was accompanied by a decrease in AChE activity at different stages of adaptation to hypoxia induced by IHT (days 5, 10, and 14). Thus, the IHT method significantly mobilises the reserve capacity of oxygen-dependent processes through the system of CA, ACh-AChE mediated by nitric oxide. Full article

Depression is a mental disorder that depicts a wide variety of symptoms, including mood and cognitive alterations, as well as recurrent thoughts of death or suicide. It could become the second leading cause of premature death or disability worldwide. Treatments with conventional antidepressants have several limitations in terms of effectiveness, side effects, and high costs. Therefore, medicinal plants such as Mucuna pruriens are potent candidates for treating depressive disorders. This review shows a compendium of evidence supporting the antidepressant effect of the Mucuna pruriens plant in diverse animal models. This includes the mechanisms of action underlying the antidepressant activity of the treatment concerning dopamine, serotonin, norepinephrine, reactive oxygen species, nitric oxide, cortisol, and inflammation. Clinical trials are needed to study the efficacy and safety of Mucuna pruriens for depression. Full article

Background/Objectives: 6-Shogaol is a comparatively innovative anti-Parkinson’s remedy with antioxidant and anti-inflammatory characteristics. This investigation intended to determine the role of 6-shogaol in the Parkinson’s disease (PD) paradigm in rotenone-induced rats. Methods: Thirty male Wistar rats (10–12 weeks old; 180 ± 20 g) were divided into five groups. Animals with rotenone-induced experimental PD were subsequently treated with 6-shogaol-10 at 20 mg/kg for 28 days. After the experimental duration, behavioural investigations were performed, i.e., open field test, forced swim test, rotarod test, and catalepsy test. Biochemical assessments like AChE, GSH, CAT, SOD, MDA, nitrite, ceruloplasmin, proinflammatory markers such as IL-1β, NF-κB, TNF-α, and catecholamines markers (DA, GABA, and MAO-B) were determined. The docking procedure was conducted using the AutoDock Vina docking protocol. Furthermore, histopathology was performed. Results: Rotenone significantly increased the level of MAO-B, oxidative, nitrative, and pro-inflammatory markers. However, there was a decline in ceruloplasmin, dopamine, and endogenous antioxidants. Treatment with 6-shogaol (10 and 20 mg/kg) considerably sustained the elevation of oxidative stress and inflammatory indicators and decreased AChE activity and dopamine levels. In the histology of the brain, 6-shogaol improved the neuronal structure and reduced the degeneration of neurons. Based on the binding energy values, compound 6-shogaol demonstrates a favourable binding affinity to AChE, MAO-B, DA, and GABA with respective binding energies of −8.214, −8.133, −7.396 and −6.189 kcal/mol. Conclusions: In this study, 6-shogaol exhibited neuroprotective properties against PD, which could be employed as a prospective medication for PD. Full article

Chromogranin B (CgB) is involved in the control of the cardiovascular system through the regulation of catecholamine release. Whether CgB can exert direct actions on the endothelium has not yet been clarified. Here, we aimed to investigate the effects of CgB on cell viability, mitochondrial membrane potential, reactive oxygen species (ROS), glutathione (GSH), nitric oxide (NO) release, and the cytosolic calcium concentration ([Ca²⁺]c) in human vascular endothelial cells (HUVECs) cultured under both physiological and peroxidative conditions. In HUVECs, experiments were conducted to establish the proper concentration and timing of CgB stimulation. Thereafter, specific assays were used to evaluate the response of HUVECs cultured in physiologic or oxidative stress conditions to CgB in the presence or absence of β-adrenergic receptor agonists and antagonists and intracellular pathways blockers. Analysis of cell viability, mitochondrial membrane potential, and NO release revealed that CgB was able to cause increased effects in HUVECs cultured in physiological conditions. Additionally, the same analyses performed in HUVECs cultured with H₂O₂, showed protective effects exerted by CgB, which was also able to counteract ROS release and maintain GSH levels. Furthermore, CgB played a dual role on the [Ca²⁺]c depending on the physiological or peroxidative cell culturing conditions. In conclusion, our data provide new information about the direct role of CgB in the physiological regulation of endothelial function and highlight its potential as a protective agent against peroxidative conditions, such as those found in cardiovascular diseases. Full article