Dopamine Secretion Research Articles

8683 Composite Pheochromocytoma/Paraganglioma-Ganglioneuroma: Biochemical And Radiological Features

Abstract Disclosure: S. Agarwal: None. A.P. Dackiw: None. F. Nwariaku: None. J.E. Mosquera: None. L. Jia: None. M.G. Roden: None. O. Hamidi: Advisory Board Member; Self; Corcept Therapeutics. Introduction: Composite pheochromocytoma/paraganglioma with ganglioneuroma (PHEO-GN or PGL-GN) is a rare tumor consisting of chromaffin cells or ganglia tissue combined with a developmentally related neurogenic tumor. Composite tumors can be present in up to 10% of PHEO and are rare with just over 100 cases reported in published literature. We present a case series of patients with PHEO-GN and PGL-GN seen at our tertiary care center to examine their natural history, clinical, radiological, and biochemical characteristics. Methods: We conducted a retrospective longitudinal follow-up study of consecutive adult patients with histologically-proven PHEO-GN and PGL-GN seen between 2013 and 2023. We collected and summarized data on demographics, laboratory findings, radiological results, and clinical outcomes. Results: The cohort comprised 10 patients (60% women): 8 with PHEO-GN (1 diagnosed on autopsy), 1 with PGL-GN, and 1 with PHEO-ganglioneuroblastoma. The median age at diagnosis was 47 years (interquartile range [IQR], 35-60). Most (80%) tumors were discovered incidentally. The prevalence of a genetic syndrome was 40% and included multiple endocrine neoplasia (MEN) 2A, MEN 4, Neurofibromatosis 1, and hereditary PHEO-PGL syndrome due to succinate dehydrogenase type B gene mutation. Nine patients (90%) had biochemically functional tumors with adrenergic biochemical phenotype in 89% and noradrenergic in 11%. The tumor associated with MEN 4 also had dopamine secretion. The median elevation above the upper normal limit of plasma metanephrine was 7.4 (IQR, 1.6-12), 24-hour urine metanephrine was 7.12 (IQR, 3.7-8.8), plasma normetanephrine was 1.7 (IQR, 1.5-1.9), and 24-hour urine normetanephrine was 2.9 (IQR, 2.4-3.5). The median tumor size at the time of diagnosis was 4.2 cm (IQR, 3.3-5.2). The median pre-contrast HU on CT imaging was 37 HU (IQR, 20-40). The median time to surgical excision from the diagnosis was 2.7 months (IQR, 1.9-4.6). All patients that underwent surgery were alive without recurrence of disease at last follow-up visit with a median follow-up of 14.5 months (IQR, 0.5-18.4). Conclusions We present a series of 10 consecutive patients with composite PHEO-GN and PGL-GN. The prevalence of genetic syndrome (40%) was much higher than previously reported (up to 25% in prior reports). PHEO or PGL component of these tumors is commonly biochemically functional with metanephrine and normetanephrine elevation commonly seen. Metastatic or recurrent disease was not observed in our cohort, suggesting favorable outcomes after surgical resection. Presentation: 6/2/2024

Irritable Bowel Syndrome - current state of knowledge

Introduction and objective: Irritable bowel syndrome (IBS) is a common gastroenterological disorder affecting 9% to 23% of the population worldwide. The disease causes recurrent abdominal pain and abnormal bowel movements without visible anatomical or biochemical changes and diagnosis is often difficult. The purpose of this paper is to analyze the current knowledge of the pathophysiology, risk factors, diagnosis and treatment of IBS. Review methods: The literature available in the PubMed database was reviewed using the following key words: "irritable bowel syndrome," "constipation," "diarrhea", "abdominal pain", "diagnostics", "treatment". 49 articles were included in the review and 80% were from 2016-2024. Current state of knowledge: The pathophysiology of IBS is not fully understood, but it is recognized that the disease is a disorder of the gut-brain axis. It can lead to abnormal secretion of serotonin and dopamine, which affects symptoms. The diagnosis of IBS is based on the Rome IV Criteria, defining the characteristics and severity of symptoms. Summary: IBS is a disorder that significantly affects quality of life. Diagnosis is based on the exclusion of organic diseases and meeting certain criteria. Treatment includes both dietary modification and pharmacotherapy aimed at relieving symptoms. Despite advances in research, the pathophysiology of IBS is still not fully understood, making it difficult to develop effective treatments.

Assessment of Urinary Dopamine and Serotonin Metabolites in Relation to Dysbiosis Indicators in Patients with Functional Constipation.

The causes of functional constipation (FC) in adults are unclear, but changes in the gut microbiome may play an important role. The present study aimed to assess the relationship between urinary metabolites of dopamine and serotonin and some dysbiosis indicators in patients with FC. The study included 40 healthy women and 40 women with FC aged 21-46 years. Urinary levels of homovanillic acid (HVA), 5-hydoxyindoleacetic acid (5-HIAA), p-hydroxyphenylacetic acid (PhAc), and 3-indoxyl sulfate, as final metabolites of dopamine, serotonin, and indole pathway, respectively, were determined using the LC-Ms/Ms method. However, hydrogen-methane and ammonia breath tests were performed. The GA-map Dysbiosis Test was used to identify and characterize the dysbiosis index (DI). In patients with FC, the DI was significantly higher than in the control group: 4.05 ± 0.53 vs. 1.52 ± 0.81 points (p < 0.001), but the number of many types of bacteria varied among individuals. The levels of HVA were higher, while 5-HIAA levels were lower in patients. Moreover, the HVA/5-HIAA ratio had a positive correlation with DI as well as with the severity of symptoms. In patients with functional constipation, the balance in dopamine and serotonin secretion is disturbed, which is associated with changes in the gut microbiome.

Adjusting Paper Device Properties for Bioelectrochemical Analysis and 3D Cell Culture

Context- Paper is an innovative material for cell culture due to its biocompatibility, its inert chemical properties and its low-cost. Paper is already used in many biomedical applications such as immunoassays and, more recently, as affordable electrochemical sensors. In this context, tuning the properties of paper devices can achieve better, more efficient and user-friendly assays for biomedical applications. Here, and by modifying the electrochemical properties of paper electrochemical devices, it is possible to create electrodes that can detect neurotransmitters, a critical type of biomolecules involved in neuronal communication. Dopamine is a neurotransmitter involved in reward and addiction and a molecule of considerable scientific interest. Dopamine is secreted in the brain by dopaminergic neurons. However, the fine chemical mechanisms of neuron networks are still obscure. Being able to spatially measure dopamine secretion, in response to activation of precise neuronal regions in a unique system, can lead to a better understanding of neuronal dynamics, as well as their response to drug alterations. Proposing a research model describing neuronal chemical function in a network will therefore help shining light on their mechanisms and testing new neuropharmacological solutions. Developing new tools for the analytical electrochemistry of the brain will make quantitative neuro-analysis more accessible, thus paving the way for a better understanding of the chemical mechanisms of the brain. Tuning paper electrode for neurochemical analysis- Conductive inks, i.e. conductive polymer poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) and carbon nanotubes (CNT) suspensions, were used to improve the detection of dopamine at paper-based electrodes. The physical and chemical properties of different preparations and mixtures of inks were considered. Solvent secondary doping, a common technique for PEDOT-PSS based electrode, was used to improve the electrical properties of the electrodes. Ferrocyanide electroanalysis was used to benchmark 10 different electrode preparations, revealing that combining CNT and PEDOT-PSS improves the electroactivity of the surface of the sensor. Interestingly, it was found that CNT has a doping effect on PEDOT-PSS, leading to improved electrochemical properties. Finally, these electrodes were tested for dopamine detection. It was found that combining PEDOT-PSS and CNT in the surface layer of ink deposited on the paper electrode allows for lower capacitance, higher anodic current as well as better fouling resistance. Figure 1 presents a CV voltammogram for Dopamine obtained with a paper electrode. Overall, this strategy improves the sensitivity of the assay. Growing neurons on paper- Paper-based devices can also be used for cell culture. Cell on paper constructs are 3D cell culture models that are more suitable to study cell in a biomimetic 3D environment, thus better recapitulating their functions and biology. By carefully modifying the surface of the paper devices, it is possible to adjust their biocompatible properties to ameliorate the survival rate of cell culture on paper. This opens the possibility to achieve neuronal cell culture on paper. We will present different paper preparations compatible with murine dopaminergic maintenance. The neurons were maintained alive for several days of culture. We were able to effectively observe and study neurons in a 3D paper environment and quantify the growth of their processes. Figure 1 : Electrochemical detection of Dopamine for 20 cycles. Working electrode is a paper electrode with PEDOT:PSS and CNT conductive inks, shown on the right, scale is 1 cm. The reference electrode is an Ag/AgCl electrode, and the counter electrode is a platinum electrode. Scan rate is 0.02 Vs-1. Figure 1

Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation

Parkinson's disease is a progressive neurodegenerative disease that affects the motor and non-motor circuits of the brain. Currently, there are no promising therapeutic measures for Parkinson's disease, and most strategies designed to alleviate the Parkinson's disease are palliative. The dearth of therapeutic interventions in Parkinson's disease has driven attention in the search for targets that may augment dopamine secretion, promote differentiation towards dopaminergic neuronal lineage, or aid in neuroprotection from neuronal stress and inflammation, and prevent Parkinson's disease associated motor impairment and behavioural chaos.The study first reports that Rev-erbα plays an important role in regulating the differentiation of undifferentiated neuronal cells towards dopaminergic neurons through abating Sox2 expression in human SH-SY5Y cells. Rev-erbα directly binds to the human Sox2 promoter region and represses their expression to promote differentiation towards dopaminergic neurons. We have reported a novel mechanism of Rev-erbα which effectively abrogates 1-methyl-4-phenylpyridinium induced cytotoxicity, inflammation, and oxidative stress, exerted a beneficial effect on transmembrane potential, and suppressed apoptosis in the neuronal in vitro model of Parkinson's disease.Rev-erbα ligand SR9011 was observed to ease the disease severity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mouse model of Parkinson's disease. Rev-erbα alleviates the locomotor behavioural impairment, prevents cognitive decline and promotes motor coordination in mice. Administration of Rev-erbα ligand also helps in replenishing the dopaminergic neurons and abrogating the neurotoxin mediated toxicity in an in vitro and in vivo Parkinson's disease model.We conclude that Rev-erbα emerges as a moonlighting nuclear receptor that could be targeted in the treatment and alleviation of Parkinson disease.

Stimulatory effect of eurycomanone from Eurycoma longifolia Jack roots on dopamine secretion in human neuroblastoma SH-SY5Y cell line

Eurycomanone has been identified as the major bioactive compound contributing to Eurycoma longifolia (EL) aphrodisiac activity, however, its mechanism of action remains obscured. Presently, eurycomanone was isolated from EL root extract and its molecular structure was identified. The human neuroblastoma SH-SY5Y cell line was differentiated into human dopaminergic neuron-like cells. Exogenous dopamine levels from the differentiated SH-SY5Y cells were quantified following the treatment of 5, 10, 15 μM of eurycomanone and 10 μM clorgyline as positive control. Dopamine secretion was significantly increased in a dose-dependent manner, compared to the vehicle control (p < .01) in differentiated SH-SY5Y cells. Dopamine concentration stimulated by 15 μM eurycomanone was significantly higher than clorgyline (p < .05), an inhibitor of monoamine oxidase A that suppresses dopamine catabolism. In conclusion, eurycomanone stimulated dopamine release of human SH-SY5Y neuron-like cells, which could be one of the mechanisms that underpin the aphrodisiac properties of the plant.

Boosting physical performance in SD rats through brain-targeted delivery of caffeine-loaded transferrin liposomes

This study aimed to explore the impact of caffeine (CAF) encapsulated in transferrin-modified, sterically-stabilized liposomes (Tf-SSL) on the physical performance of rats, specifically forelimb grip strength, running, and swimming. The brain-targeted drug delivery system, Tf-SSL, was used for the administration of caffeine. 168 male Sprague-Dawley (SD) rats were randomly assigned to different groups, including swimming, running, running wheel, and strength groups. Each group was further subdivided into high, medium, and low dose free caffeine (HCAF, MCAF, LCAF) and Tf-SSL CAF groups, along with a control group (CON). The strength, swimming, and running groups underwent training for four weeks, three times per week. The running wheel group was placed in rearing cages for a one-week adaptation period. After the final training session, the resistance, swimming, running, and running wheel exercise capacities of the rats were tested. The rats were administered treatment via tail vein injection, while the blank CON group received 0.9 % saline solution without treatment throughout the entire process. The results demonstrated a Tf-SSL CAF group encapsulation rate of 70.58 ± 5.14 %. Increasing the concentration of supplemented caffeine led to enhanced forelimb grip strength in rats, with significant differences observed in HCAF alone group, medium-dose Tf-SSL CAF (MTf-SSL CAF), and high-dose Tf-SSL CAF (HTf-SSL CAF) groups compared to the CON group. In the running and swimming experiments, higher caffeine supplementation concentrations correlated with increased running and swimming time to exhaustion, and the MTf-SSL CAF group showed longer running and swimming time compared to the HCAF alone group. The results of rat striatal dopamine levels indicated that increased caffeine supplementation concentrations led to higher dopamine secretion, with significantly different striatal concentrations in the HCAF group, MTf-SSL CAF group, and HTf-SSL CAF group compared to the CON group. The running wheel experiment revealed that rats in the medium- and high-dose Tf-SSL CAF groups exhibited greater 6-h running distances than the HCAF group and CON group. In conclusion, caffeine supplementation improved the physical performance of rats, with the high concentration CAF group outperforming the low and medium concentration groups. Furthermore, Tf-SSL CAF demonstrated superior physical enhancement compared to caffeine supplementation alone.

The rs4354668 polymorphism in the SLC1A2 gene for the EAAT2 glutamate transporter is associated with an increased risk of harmful drug use - an exploratory study on a university student population.

Evidence suggests that decreased dopamine secretion in mesocorticolimbic pathways could predispose to increased susceptibility to substance addiction. It has been proposed to define such a phenomenon as the reward deficit syndrome (RDS). Dopaminergic projections of the reward system receive glutaminergic projections from cortex. Research indicates that a reduction in the stimulating glutamatergic transmission on the dopaminergic system could represent an alternative phenotype of RDS. Potential source of this type of abnormality is glutamate reuptake which depends on excitatory amino acid transport proteins (EAAT) function. The most important of them is EAAT2, polymorphisms of which have been linked to several mental disorders. We analyzed the genetic and psychometric data of 125 young adults (n = 125) for the effect of the rs4354668 polymorphism of the SLC1A2 gene for EAAT2 on the risky or harmful drug use (RHDU). After exploratory analysis we used logistic regression models to assess the probability of RHDU in individual groups. In the final model T/T variant of rs4354668 was significantly associated with a lower probability of RHDU occurrence compared to G/G variant (OR: 0.021; 95% CI: 0.001 - 0.275; p = 0.009). Other significant predictors of RHDU were smoking status and risky or harmful drinking of alcohol. The results obtained may indicate a possible relationship of the risk of harmful drug use with variants of the rs4354668 polymorphism of the SLC1A2 gene for EAAT2. Subjects with the T/T variant of this polymorphism appear to be less at risk of developing drug use disorders.

Human amniotic epithelial stem cell-derived dopaminergic neuron-like cells ameliorate motor dysfunction in a rat model of Parkinson's disease

AimsParkinson's disease (PD) remains a substantial clinical challenge due to the progressive loss of midbrain dopaminergic (DA) neurons in nigrostriatal pathway. In this study, human amniotic epithelial stem cells (hAESCs)-derived dopaminergic neuron-like cells (hAESCs-DNLCs) were generated, with the aim of providing new therapeutic approach to PD. Materials and methodshAESCs, which were isolated from discarded placentas, were induced to differentiate into hAESCs-DNLCs by following a “two stages” induction protocol. The differentiation efficiency was assessed by quantitative real-time PCR (qRT-PCR), immunocytochemistry (ICC), and ELISA. Immunogenicity, cell viability and tumorigenicity of hAESCs-DNLC were analyzed before in vivo experiments. Subsequently, hAESCs-DNLCs were transplanted into PD rats, behavioral tests were monitored after graft, and the regeneration of DA neurons was detected by immunohistochemistry (IHC). Furthermore, to trace hAESCs-DNLCs in vivo, cells were pre-labeled with PKH67 green fluorescence. Key findingshAESCs were positive for pluripotent markers and highly expressed neural stem cells (NSCs) markers. Based on this, we established an induction method reliably generates hAESCs-DNLCs, which was evidenced by epithelium-to-neuron morphological changes, elevated expressions of neuronal and DA neuronal markers, and increased secretion of dopamine. Moreover, hAESCs-DNLCs maintained high cell viability, no tumorigenicity and low immunogenicity, suggesting hAESCs-DNLCs an attractive implant for PD therapy. Transplantation of hAESCs-DNLCs into PD rats significantly ameliorated motor disorders, as well as enhanced the reinnervation of TH+ DA neurons in nigrostriatal pathway. SignificanceOur study has demonstrated evident therapeutic effects of hAESCs-DNLCs, and provides a safe and promising solution for PD.

Epigenetic Effects of Finasteride on Dopaminergic Signaling Pathways: A potential contributor to Post-Finasteride Syndrome

Dopamine, a widely-distributed neurotransmitter in the brain and elsewhere, is important for regulating reward-motivated behavior, sexual impetus, concentration, pleasure, emotions, and genital arousal. Findings have previously implicated aberrant dopaminergic neurotransmission in mental disorders, as well as sexual and erectile dysfunction. To evaluate the epigenetic effects of finasteride on dopaminergic signaling pathways, we treated human Leydig cells with finasteride and identified several dopaminergic pathways that were altered by differential methylation of component genes. These genes included those involved in the regulation of dopamine secretion and transport (OR56A4, OR13F1 and SYT4), the Phospholipase C-activating dopamine receptor signaling pathway (OR56A4 and OR13F1), the dopaminergic synapse (CALML4, COMT, GNAI2, GNAS, GNG10, GRIA1, GSK3A, GSK3B, KCNJ9, PPP2R2C, PPP2R3B, PPP2R3C, PPP2R5A, PPP2R5E) and the dopamine receptor activity and binding pathway (OR56A4, OR13F1). This alteration of gene methylation suggests a potential role of altered epigenetic regulation of dopaminergic pathways in the etiology and pathophysiology of post-finasteride syndrome (PFS), which should be further investigated. National Institutes of Health (NIH) R25 Resource Grant (1 R25 AG047843-01) to ABC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Single-Cell Nuclear Sequencing Atlas Revealed the Induction of Parkinson's Disease by RELN+ Neuron 3 and the Gene Regulatory Network of MSRA.

To determine the cell types that promoted the progression of Parkinson's disease (PD) using the substantia nigra in the brain tissues derived from patients with PD and normal controls. PD is an incurable neurodegenerative disease that threatens the physical activity of the aging population, and the complex molecular mechanisms remain be comprehensively elucidated. To describe potential disease-promoting cell types in PD and to provide a theoretical basis. Single-cell nuclear sequencing data of nine PD samples and control samples from Gene Expression Omnibus (GEO) were included, and heterogeneous cell subpopulations in the substantia nigra were identified by annotation analysis. Potential pathogenic cell subpopulations of PD were determined based on the expression data of marker genes. Cell differentiation trajectories and communication networks were generated by Pseudotime trajectory analysis and cell communication analysis. Furthermore, single-- cell regulatory network inference and clustering (SCENIC) analysis was conducted to determine the regulatory network of transcription factor-target genes in PD. Among the nine cell subpopulations classified, RELN+neuron 3 showed reduced abundance and dopamine secretion capacity in PD and was therefore considered as a promoter of PD pathogenesis and progression. The regulatory network of MSRA action was involved in the developmental process of cells in the central nervous system, indicating that MSRA and its targets might serve as potential therapeutic targets for PD. RELN+neuron 3 had two directions of differentiation, specifically, branch 1 exhibited a high apoptotic profile and branch 2 exhibited a high cell death profile. In addition, the intensity of EPHA and EPHB signaling was attenuated between RELN+neuron 3 and other cell subpopulations. To conclude, this study identified a subpopulation of RELN+neuron 3 cells with markedly reduced abundance in the brain substantia nigra in PD. The MSRA-involved gene regulatory networks was considered as a novel therapeutic network for PD.

Coupled action potential and calcium dynamics underlie robust spontaneous firing in dopaminergic neurons

Dopaminergic neurons are specialized cells in the substantia nigra, tasked with dopamine secretion. This secretion relies on intracellular calcium signaling coupled to neuronal electrical activity. These neurons are known to display spontaneous calcium oscillations in-vitro and in-vivo, even in synaptic isolation, controlling the basal dopamine levels. Here we outline a kinetic model for the ion exchange across the neuronal plasma membrane. Crucially, we relax the assumption of constant, cytoplasmic sodium and potassium concentration. We show that sodium-potassium dynamics are strongly coupled to calcium dynamics and are essential for the robustness of spontaneous firing frequency. The model predicts several regimes of electrical activity, including tonic and ‘burst’ oscillations, and predicts the switch between those in response to perturbations. ‘Bursting’ correlates with increased calcium amplitudes, while maintaining constant average, allowing for a vast change in the calcium signal responsible for dopamine secretion. All the above traits provide the flexibility to create rich action potential dynamics that are crucial for cellular function.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Goldnanostructures anda Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the capacity to synthesize, store, and release catecholamines as well as theirunlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling.Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells)were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Expression of human Ras-related protein Rab39B variant T168K in Caenorhabditis elegans leads to motor dysfunction and dopaminergic neuron degeneration

Human RAB39B gene is related to familial early-onset Parkinson disease. In early adulthood, men with the RAB39B c.503C > A (Thr168Lys, p. T168K) mutation develop typical tremor, bradykinesia, and alpha-synuclein accumulation. We investigated the pathological mechanism of RAB39B T168K in a Caenorhabditis elegans model. In early adult C. elegans, RAB39B T168K led to dopaminergic neuron degeneration that presented as disrupted dendrites and blunt neuronal cells. Abnormal dopamine secretion was inferred from a decline in motor function and a positive basal slowing phenotype. Dopamine-associated tests confirmed that synthesis and recycling of dopamine were normal. The RAB39B T168K mutation might impair dopamine vesicular transmission from the presynaptic membrane to the synaptic gap in dopaminergic neurons. The release-dependent feedback mechanism in neurotransmitters regulates the balance of receptor activities. Protein-protein interactions network analysis revealed that RAB39B may also function in lysosomal degradation and autophagy. Impaired disposal of misfolded α-synuclein eventually leads to protein aggregation. Thus, like other members of the Rab family, RAB39B may be involved in vesicular transport associated with dopamine secretion and α-synuclein clearance.

Chemoproteomic analysis of the pharmacological properties of vitamin В12 derivatives

Background. Chemical derivatives of vitamin B12 are characterized by a wide range of pharmacological effects. It is important to learn how to establish relationships between changes of the corrin ring structure in vitamin B12 derivatives and changes in pharmacological properties.Objective: to evaluate the interaction of six vitamin B12 derivatives (aquacobalamin, diaquacobinamide, aquacyano-forms of heptaethanolamine, heptaethylenediamine, heptamethyl and heptabutyl cobyrinates) with human proteome proteins.Material and methods. Using the method of chemoinformational (chemoproteomic) analysis, implemented within the framework of algebraic recognition theory and topological data analysis, the constants of half-maximal inhibitory concentration (IC50) and half-maximal effective concentration (EC50) of human proteome proteins were assessed.Results. Significant differences were found in the interactions of the studied molecules with 1200 proteins. It was shown that the chemoproteomic profiles of each of the compounds form three groups of molecules with similar proteomic properties: (1) aquacobalamin, (2) diaquacobinamide, aquacyano-forms of heptaethanolamine and heptaethylenediamine cobyrinates, (3) aquacyano-forms of heptamethyl and heptabutyl cobyrinates. A more detailed analysis of the chemoproteomic profiles of the studied compounds using the GO (Gene Ontology) nomenclature of biological functions of proteins made it possible to identify functional GO categories indicating differences in the biological effects of the studied compounds: neuroprotective regulation of neurotransmitter activity (serotonin receptor activity, cholinergic synapses, regulation of dopamine secretion, receptor thyroid hormones), reduction of inflammation (inhibition of cytokine biosynthesis, including tumor necrosis factor alpha and interleukin 1 beta, I-kappa-B kinases / nuclear factor kappa В, leukocyte migration), etc.Conclusion. The profiles of differences in the pharmacological properties of the studied compounds with respect to their effects on neuroprotection, neurotransmitter metabolism, and inflammation were identified and described.

Epidemiological, Clinical and Biological Hemogram Features in a Cohort of Neuroendocrine Tumor Patients.

We conducted a retrospective study based on 55 patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs)-gastric (G-NET), small bowel (SB-NET) and colonic (C-NET), hospitalized and evaluated within the Surgical, Gastroenterology and Internal Medicine Clinics, in The Clinical Emergency County Hospital Craiova, between May 2016 and April 2024. We aimed in this study to analyze the epidemiological aspects and clinical characteristics of patients with GEP-NETs. In our study group, the patients' ages were between 39-82 years, with a mean of 66.40 (±12.46) years. The incidence of GEP-NETs cases in young patients was insignificant low-1 case. 45.46% of all patients lived in urban areas. 16.36% were G-NET, 14,54 were SB-NET and 69.09% were C-NET. The GEP-NETs diagnosis was established by immunohistochemistry features. Also, we observed that the most frequency localization was on the ascending colon, while the rarest on the colon it is located on the transverse colon and the rarest is on the small bowel, in spite of the generally literature data. From the C-NET group, 49.09% have been presented arterial hypertension probable explained by serotonin and dopamine secretion an inflammatory through phenotype expression and just one patient has been presented an erythematous psoriasis, which could be also explained by the same neurotransmitter's involvement as a possible purposed mechanism. The results obtained in our study demonstrate that could be a common profile of GEP-NETs patients through epidemiological general information and clinical characteristics. Also, we demonstrate that, in the last years, the incidence increased for the GEP-NETs.

Rapid electrochemical detection of L-lactate in Baijiu affecting serotonin and dopamine secretion in mice.

Baijiu, a traditional Chinese alcoholic beverage, carries China's rich historical and cultural heritage. Consumers experience varying levels of relaxation and pleasure after consuming different types of Baijiu, with the biological basis of delectation influenced by serotonin and dopamine. In this study, we prepared carbon fiber electrodes modified with surface decorated gold nanoparticles to directly measure the electrochemical response signals in the serum of mice before and after gavage with different types of Baijiu. It was observed that the serum signal change in mice after consuming Baijiu sample 1 (J1) was higher than that of the other two types of Baijiu. Consequently, trace flavor compounds in the Baijiu samples were detected using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), revealing the highest content of L-lactic acid in J1. Mice were intraperitoneally injected with 200 mg kg-1 of L-lactic acid. The changes in dopamine and serotonin in the serum of the injected mice were monitored using a biosensor, and the results were compared with the results of high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS). The findings confirmed that L-lactic acid could indeed stimulate the secretion of both neurotransmitters in mice, suggesting that the trace components in J1 may even exhibit synergistic effects. This study contributes to a deeper understanding of the effects of Baijiu on the body and provides a scientific basis for the production and consumption of Baijiu.

Preparation of carbon quantum dot fluorescent probe from waste fruit peel and its use for the detection of dopamine.

Carbon quantum dots (CQDs), as a new type of fluorescent nanomaterial, are widely used in the detection of small molecules. Abnormal dopamine secretion can lead to diseases such as Parkinson's disease and schizophrenia. Therefore, it is highly significant to detect dopamine levels in the human body. Using discarded fruit peels to prepare carbon quantum dots can achieve the reuse of kitchen waste, reduce pollution, and create value. Nitrogen-doped carbon quantum dots (N-CQDs) were prepared using the hydrothermal method, with orange peel as the raw material. The fluorescence quantum yield of N-CQDs reached a high value of 35.37% after optimizing the temperature, reaction time, and ethylenediamine dosage. N-CQDs were characterized using various techniques, including ultraviolet visible (UV-vis) spectroscopy, fluorescence spectrophotometer (PL), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). These analyses confirmed the successful doping of nitrogen in the CQDs. The DA concentration ranged from 0 to 300 μmol L-1, and the linear equation for fluorescence quenching of N-CQDs was F/F0 = -0.0056c + 0.98647, with an R2 value of 0.99071. The detection limit was 0.168 μmol L-1. The recovery and precision of dopamine in rabbit serum were 98% to 103% and 2% to 6%, respectively. The prepared N-CQDs could be used as a fluorescent probe to effectively detect DA.

The peptide Acein promotes dopamine secretion through clec-126 to extend the lifespan of elderly C. elegans.

Dopamine plays a crucial role in regulating brain activity and movement and modulating human behavior, cognition and mood. Regulating dopamine signaling may improve cognitive abilities and physical functions during aging. Acein, a nonapeptide of sequence H-Pro-Pro-Thr-Thr-Thr-Lys-Phe-Ala-Ala-OH is able to stimulate dopamine secretion in the brain. By using genetic editing and lifespan investigation in C. elegans, we showed that the lack of the C-type lectin domain-containing protein clec-126 significantly suppressed the aging phenotype and prolonged lifespan, while overexpression of clec-126 promoted aging-related phenotypes and accelerated the aging process. We examined the aging phenotype of C. elegans and showed that Acein could induce a decrease in clec-126 expression, prolonging the lifespan of aged C. elegans. The mechanism proceeds through the Acein-induced stimulation of dopamine secretion that ameliorates motor function decline and extends the healthy lifespan of aged C. elegans. In addition, we also observed an increase in brood number. Our study has shown that Acein regulates dopamine secretion and has good antiaging activity by decreasing clec-126 expression.

Molecular Dynamics Simulation of Serotonin Transport Protein Complex with 6-Hydroxy-1-Methyl-1,2,3,4-Tetrahydro-β-Carboline Ligand from Chocolate (Theobroma cacao L.) Isolate

6-hydroxy-1-methyl1,2,3,4-tetrahydro-β-carboline (6OHMTHβC) is a chocolate derivate that has antidepressant potency. It can increase dopamine and serotonin secretion, which leads to mood improvement. This method was carried out using computational molecular docking simulations (in silico). The research design was computational-based exploratory descriptive. The results of molecular docking showed the lowest energy score and the backbone RMSD value ≤2Å. The procedure performed was 6AWP receptor docking without ligand, with native ligand (6OHMTHβC), and with reference ligand (fluvoxamine). This study also performed molecular docking simulations of 6OHMTHβC towards 6AWP to find compounds in the receptor binding pocket. This study also performed dynamics simulations and identified the molecular determinants using PyPLIF-HIPPOS and YASARA Structure software 20.1.24.10 with the Windows 10 operating system. This study succeeded in determining the stability of the dynamics simulation of the serotonin transport protein complex with the reference ligand 6OHMTHβC for 50 ns, and this result corresponds to the RMSD value and binding energy. The determination of binding energy (BE) was calculated from the BE calculation available at YASARA and Ubuntu. The binding energy value of the original ligand was -11.6590 kJ/mol, and the reference ligand was -83880 kJ/mol. The highest RMSD value of the original ligand was 1.39292Å, while the RMSD value of the reference ligand was 1.71072Å. The essential amino acid carried out was 438Ser with hydrogen bond interactions, so 6OHMTHβC was considered a competent antidepressant candidate.