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1.
Nutr J ; 23(1): 28, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38429722

RESUMO

BACKGROUND: The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes. METHODS: In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort. Circulating primary and secondary unconjugated BAs and their taurine- or glycine-conjugates were measured using ultraperformance liquid chromatography-tandem mass spectrometry. CKD was defined as eGFR < 60 ml/min per 1.73 m2. Logistic regression model was used to compute odds ratio (OR) and 95% confidence interval (CI). RESULTS: After adjusting for multiple testing, higher levels of total primary BAs (OR per standard deviation [SD] increment: 0.78; 95% CI: 0.65-0.92), cholate (OR per SD: 0.78; 95% CI: 0.66-0.92), chenodeoxycholate (OR per SD: 0.81; 95% CI: 0.69-0.96), glycocholate (OR per SD: 0.81; 95% CI: 0.68-0.96), and glycochenodeoxycholate (OR per SD: 0.82; 95% CI: 0.69-0.97) were associated with a lower likelihood of having CKD in patients with newly diagnosed type 2 diabetes. No significant relationships between secondary BAs and odds of CKD were observed. CONCLUSIONS: Our findings showed that higher concentrations of circulating unconjugated primary BAs and their glycine-conjugates, but not taurine-conjugates or secondary BAs, were associated with lower odds of having CKD in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Ácidos e Sais Biliares , Estudos Transversais , Estudos Prospectivos , Diabetes Mellitus Tipo 2/epidemiologia , Taurina/química , Glicina , Insuficiência Renal Crônica/epidemiologia
2.
Nutrients ; 16(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474873

RESUMO

Endocardial endothelium (EE) is a layer of cells covering the cardiac cavities and modulates cardiomyocyte function. This cell type releases several cardioactive factors, including Angiotensin II (Ang II). This octopeptide is known to induce cardiac hypertrophy. However, whether this circulating factor also induces EE hypertrophy is not known. Taurine is known to prevent cardiac hypertrophy. Whether this endogenous antioxidant prevents the effect of Ang II on human EE (hEE) will be verified. Using quantitative fluorescent probe imaging for calcium and reactive oxygen species (ROS), our results show that Ang II induces (10-7 M, 48 h treatment) an increase in hEE cell (hEEC) volume and its nucleus. Pretreatment with 20 mM of taurine prevents morphological remodeling and increases intracellular calcium and ROS. These results suggest that the reported Ang II induces cardiac hypertrophy is associated with hEEC hypertrophy. This later effect is prevented by taurine by reducing intracellular calcium and ROS overloads. Thus, taurine could be an excellent tool for preventing Ang II-induced remodeling of hEECs.


Assuntos
Angiotensina II , Cálcio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Angiotensina II/metabolismo , Cálcio/metabolismo , Taurina/farmacologia , Cardiomegalia/metabolismo , Miócitos Cardíacos , Endotélio/metabolismo
3.
J Zoo Wildl Med ; 55(1): 155-163, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38453498

RESUMO

Meerkats (Suricata suricatta) housed at two accredited zoological institutions in the United States were evaluated via echocardiography, thoracic radiography, and blood biomarkers-taurine and feline N-terminal pro-B-type natriuretic peptide-to determine the prevalence and severity of dilated cardiomyopathy (DCM) in both populations. In total, 24 meerkats were evaluated and 7 were diagnosed with DCM based on the following parameters: left ventricular internal diameter at end diastole > 1.30 cm, left ventricular internal diameter at end systole > 1.10 cm, and a fractional shortening of <18%. Echocardiographic parameters were identified and reported for normal and affected meerkats, whereas thoracic radiographs were not useful for screening for DCM. Meerkats with DCM were treated with pimobendan and/or benazepril and furosemide if indicated. Seven meerkats died during the study period, with the majority exhibiting myocardial fibrosis. Of the blood parameters tested, elevated taurine levels were associated with DCM. Further research is necessary to characterize the etiology of DCM in meerkats.


Assuntos
Cardiomiopatia Dilatada , Doenças do Gato , Herpestidae , Humanos , Gatos , Animais , Cardiomiopatia Dilatada/veterinária , Ecocardiografia/veterinária , Radiografia , Taurina
4.
Arch Toxicol ; 98(4): 1135-1149, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38446233

RESUMO

A-series agent A-234 belongs to a new generation of nerve agents. The poisoning of a former Russian spy Sergei Skripal and his daughter in Salisbury, England, in March 2018 led to the inclusion of A-234 and other A-series agents into the Chemical Weapons Convention. Even though five years have already passed, there is still very little information on its chemical properties, biological activities, and treatment options with established antidotes. In this article, we first assessed A-234 stability in neutral pH for subsequent experiments. Then, we determined its inhibitory potential towards human recombinant acetylcholinesterase (HssAChE; EC 3.1.1.7) and butyrylcholinesterase (HssBChE; EC 3.1.1.8), the ability of HI-6, obidoxime, pralidoxime, methoxime, and trimedoxime to reactivate inhibited cholinesterases (ChEs), its toxicity in rats and therapeutic effects of different antidotal approaches. Finally, we utilized molecular dynamics to explain our findings. The results of spontaneous A-234 hydrolysis showed a slow process with a reaction rate displaying a triphasic course during the first 72 h (the residual concentration 86.2%). A-234 was found to be a potent inhibitor of both human ChEs (HssAChE IC50 = 0.101 ± 0.003 µM and HssBChE IC50 = 0.036 ± 0.002 µM), whereas the five marketed oximes have negligible reactivation ability toward A-234-inhibited HssAChE and HssBChE. The acute toxicity of A-234 is comparable to that of VX and in the context of therapy, atropine and diazepam effectively mitigate A-234 lethality. Even though oxime administration may induce minor improvements, selected oximes (HI-6 and methoxime) do not reactivate ChEs in vivo. Molecular dynamics implies that all marketed oximes are weak nucleophiles, which may explain the failure to reactivate the A-234 phosphorus-serine oxygen bond characterized by low partial charge, in particular, HI-6 and trimedoxime oxime oxygen may not be able to effectively approach the A-234 phosphorus, while pralidoxime displayed low interaction energy. This study is the first to provide essential experimental preclinical data on the A-234 compound.


Assuntos
Reativadores da Colinesterase , Compostos de Pralidoxima , Taurina/análogos & derivados , Ratos , Humanos , Animais , Reativadores da Colinesterase/farmacologia , Trimedoxima/farmacologia , Butirilcolinesterase , Acetilcolinesterase , Oximas/farmacologia , Compostos de Piridínio/farmacologia , Antídotos/farmacologia , Inibidores da Colinesterase/toxicidade , Fósforo , Oxigênio
5.
J Neuroinflammation ; 21(1): 70, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515139

RESUMO

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia-reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen-glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Proteína HMGB1 , AVC Isquêmico , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Ácido Hipocloroso , Microglia/metabolismo , Proteína HMGB1/metabolismo , Ratos Sprague-Dawley , Lesões Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Barreira Hematoencefálica/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Neurônios/metabolismo , Traumatismo por Reperfusão/metabolismo , Peroxidase/metabolismo , Taurina , Dissulfetos
6.
AAPS J ; 26(1): 25, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355847

RESUMO

Degradation of therapeutic monoclonal antibodies (mAbs) is a major concern as it affects efficacy, shelf-life, and safety of the product. Taurine, a naturally occurring amino acid, is investigated in this study as a potential mAb stabilizer with an extensive analytical characterization to monitor product degradation. Forced degradation of trastuzumab biosimilar (mAb1)-containing samples by thermal stress for 30 min resulted in high-molecular-weight species by more than 65% in sample without taurine compared to the sample with taurine. Samples containing mAb1 without taurine also resulted in higher Z-average diameter, altered protein structure, higher hydrophobicity, and lower melting temperature compared to samples with taurine. The stabilizing effect of taurine was retained at different mAb and taurine concentrations, time, temperatures, and buffers, and at the presence of polysorbate 80 (PS80). Even the lowest taurine concentration (10 mM) considered in this study, which is in the range of taurine levels in amino acid injections, resulted in enhanced mAb stability. Taurine-containing samples resulted in 90% less hemolysis than samples containing PS80. Additionally, mAb in the presence of taurine showed enhanced stability upon subjecting to stress with light of 365 nm wavelength, combination of light and H2O2, and combination of Fe2+ and H2O2, as samples containing mAb without taurine resulted in increased degradation products by more than 50% compared to samples with taurine upon subjecting to these stresses for 60 min. In conclusion, the presence of taurine enhanced physical stability of mAb by preventing aggregate formation, and the industry can consider it as a new mAb stabilizer.


Assuntos
Anticorpos Monoclonais , Taurina , Anticorpos Monoclonais/química , Peróxido de Hidrogênio , Trastuzumab , Polissorbatos/química , Excipientes , Aminoácidos
7.
BMJ Open ; 14(2): e074393, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316585

RESUMO

OBJECTIVE: To assess the uptake of services provided by community health workers who were trained as community health entrepreneurs (CHEs) for febrile illness and diarrhoea. DESIGN: A cross-sectional survey among households combined with mapping of all providers of basic medicine and primary health services in the study area. PARTICIPANTS: 1265 randomly selected households in 15 rural villages with active CHEs. SETTING: Bunyangabu district, Uganda. OUTCOME MEASURES: We describe the occurrence and care sought for fever and diarrhoea in the last 3 months by age group in the households. Care provider options included: CHE, health centre or clinic (public or private), pharmacy, drug shop and other. Geographic Information Ssystem (GIS)-based geographical measures were used to map all care providers around the active CHEs. RESULTS: Fever and diarrhoea in the last 3 months occurred most frequently in children under 5; 68% and 41.9%, respectively. For those who sought care, CHE services were used for fever among children under 5, children 5-17 and adults over 18 years of age in 34.7%, 29.9% and 25.1%, respectively. For diarrhoea among children under 5, children 5-17 and adults over 18 years of age, CHE services were used in 22.1%, 19.5% and 7.0%, respectively. For those who did not seek care from a CHE (only), drug shops were most frequently used services for both fever and diarrhoea, followed by health centres or private clinics. Many households used a combination of services, which was possible given the high density and diversity of providers found in the study area. CONCLUSIONS: CHEs play a considerable role in providing care in rural areas where they are active. The high density of informal drug shops and private clinics highlights the need for clarity on the de facto roles played by different providers in both the public and private sector to improve primary healthcare.


Assuntos
Assistência Farmacêutica , População Rural , Taurina/análogos & derivados , Criança , Adulto , Humanos , Adolescente , Estudos Transversais , Uganda/epidemiologia , Saúde Pública , Febre/epidemiologia , Febre/terapia , Diarreia/epidemiologia , Diarreia/terapia , Instituições de Assistência Ambulatorial , Serviços de Saúde Comunitária
8.
Vet Med Sci ; 10(2): e1387, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379352

RESUMO

BACKGROUND: In ovo application is the process of administering some nutrients or components into the egg. The main purpose of this application is to ensure that some nutrients are provided to chicks with a short incubation period. Few studies were conducted with taurine in fertile eggs; especially, no observation of hatchability and chick quality has been found. In addition, taurine has an anti-stress impact that fights oxidative factors. OBJECTIVE: To assess the hatchability and chick quality after in ovo taurine administration. To determine the stress that may occur as a result of in ovo application and whether taurine has a stress-reducing effect. METHODS: A total of 1200 fertile eggs from a 34-week-old broiler breeder (Ross 308) flock were categorized into 4 groups with 75 eggs per replicate: control (uninjected), taurine group (0.30 mL dissolved taurine in distilled water), sham control (sterile distilled water) and perforation (eggs perforated and then waxed). On day 14 of incubation, an in ovo injection was administered to the albumen. Data on hatching parameters and hepatic HSP70 levels were obtained using relevant formulas and western blotting, respectively. RESULTS: Control chicks exhibited higher hatchability than other groups, with the taurine group showing the lowest hatchability. The HSP70 levels were the highest in the perforation group compared to the control group. An increase of 21.37% in the taurine group and 83.45% in the sham control group was observed compared to the control group. CONCLUSIONS: The findings suggest that in ovo application may induce increased stress, whereas taurine may have positive effects in mitigating the stress caused by in ovo application.


Assuntos
Galinhas , Taurina , Animais , Taurina/farmacologia , Injeções/veterinária , Fígado , Água
9.
Zhongguo Zhong Yao Za Zhi ; 49(1): 224-231, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403355

RESUMO

This study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1ß, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.


Assuntos
Artrite Gotosa , Glucosídeos , Polifenóis , Taurina/análogos & derivados , Humanos , Ratos , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Ácido Linoleico , Ratos Sprague-Dawley , Metabolômica , Fígado/metabolismo , Citocinas , Biomarcadores/metabolismo , Glicerofosfolipídeos , Cromatografia Líquida de Alta Pressão
10.
J Pharmacol Sci ; 154(3): 175-181, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395518

RESUMO

Taurine (2-aminoethanesulfonic acid) is a free amino acid found ubiquitously and abundantly in mammalian tissues. Taurine content in the heart is approximately 20 mM, which is approximately 100 times higher than plasma concentration. The high intracellular concentration of taurine is maintained by the taurine transporter (TauT; Slc6a6). Taurine plays various roles, including the regulation of intracellular ion dynamics, calcium handling, and acting as an antioxidant in the heart. Some species, such as cats and foxes, have low taurine biosynthetic capacity, and dietary taurine deficiency can lead to disorders such as dilated cardiomyopathy and blindness. In humans, the relationship between dietary taurine deficiency and cardiomyopathy is not yet clear, but a genetic mutation related to the taurine transporter has been reported to be associated with dilated cardiomyopathy. On the other hand, many studies have shown an association between dietary taurine intake and age-related diseases. Notably, it has recently been reported that taurine declines with age and is associated with lifespan in worms and mice, as well as healthspan in mice and monkeys. In this review, we summarize the role of dietary and genetic taurine deficiency in the development of cardiomyopathy and aging.


Assuntos
Cardiomiopatia Dilatada , Humanos , Camundongos , Animais , Cardiomiopatia Dilatada/genética , Coração , Envelhecimento/genética , Taurina/metabolismo , Mamíferos/metabolismo
11.
Placenta ; 147: 59-67, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38325050

RESUMO

INTRODUCTION: Hypotaurine, a precursor to taurine, is known for its antioxidant properties and is prominently present in fetal plasma and the placenta. Our previous research revealed that ezrin-knockout mice experience fetal growth retardation, coinciding with reduced hypotaurine levels in fetal plasma. This study aims to elucidate the expression and role of hypotaurine transporters within the placenta. METHODS: We employed quantitative RT-PCR to measure mRNA expression of GAT transporter family members in the placenta during mid-to-late gestation. LC/MS/MS was used to analyze the distribution of hypotaurine in different placental subregions. Immunohistochemistry was utilized to examine the localization of GAT2 in mice. Placental hypotaurine uptake from fetal circulation was studied via umbilical perfusion in rats. RESULTS: Among hypotaurine transporters, GAT2 exhibited increased mRNA and protein expression in murine placenta during mid-to-late gestation. Notably, GAT2/Slc6a13 mRNA and hypotaurine were most concentrated in the labyrinth of murine placenta. In contrast, enzymes responsible for hypotaurine synthesis, such as cysteine dioxygenase, cysteine sulfinic acid decarboxylase, and 2-aminoethanethiol dioxygenase, showed minimal expression in the labyrinth. These findings suggest that GAT2 is a key determinant of hypotaurine levels in the placental labyrinth. Immunohistochemical examination unveiled that GAT2 was predominantly localized on the fetal-facing plasma membrane within syncytiotrophoblasts, which co-localized with ezrin. In rat umbilical perfusion experiments, the GAT2/3 and TauT inhibitor, SNAP-5114, significantly reduced hypotaurine extraction from fetal circulation to the placenta. DISCUSSION: The results suggest that GAT2 plays a pivotal role in the concentrative uptake of hypotaurine from fetal plasma within syncytiotrophoblasts of the placenta.


Assuntos
Placenta , Espectrometria de Massas em Tandem , Taurina/análogos & derivados , Ratos , Camundongos , Gravidez , Feminino , Animais , Placenta/metabolismo , Trofoblastos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Membrana Celular/metabolismo , Taurina/metabolismo , Taurina/farmacologia , Camundongos Knockout , RNA Mensageiro/metabolismo
12.
Sci Rep ; 14(1): 2686, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302509

RESUMO

Doxorubicin (DOX) is an effective anticancer drug with potent antitumour activity. However, the application of DOX is limited by its adverse reactions, such as depression. Taurine can alleviate depression induced by multiple factors. However, it is still unclear whether and how taurine improves DOX-induced depression. To address this question, the aim of this study was to explore the potential mechanism by which taurine protects against DOX-induced depression. Mice were randomly divided into three groups (n = 8): (1) the control group, (2) the DOX group, and (3) the DOX + taurine group. The open field test (OFT), elevated plus maze test, and forced swim test (FST) were first performed to assess the effects of DOX and taurine on the behaviour of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyse the possible antidepressive effect of taurine. Taurine pretreatment increased the total distance travelled and speed of mice in the OFT, increased the number of entries into the open arm and the time spent in the open arm, and reduced the immobility time in the FST. In addition, 179 differential genes and 51 differentially abundant metabolites were detected in the DOX + taurine group compared to the DOX group. Furthermore, differential genes and differentially abundant metabolites were found to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Taurine alleviated DOX-induced depressive behaviour. The various pathways identified in this study, such as the serotonergic synapse and the inflammatory mediator regulation of TRP channels, may be key regulatory pathways related to depression and antidepressant effects.


Assuntos
Depressão , Taurina , Camundongos , Animais , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/genética , Taurina/metabolismo , Doxorrubicina/toxicidade , Antidepressivos/farmacologia , Perfilação da Expressão Gênica
13.
Behav Brain Res ; 463: 114892, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38309374

RESUMO

Taurine is a non-essential ß sulfonated amino acid involved in a plethora of biological functions in the mammalian central nervous system. Taurine is easily accessible in energy drinks for human consumption. Previous preclinical and clinical reports suggest that acute systemic administration of taurine could inhibit some of the behavioral and metabolic effects of alcohol use disorder. Overall, both in rodent and human studies, acute taurine administration reduced voluntary alcohol intake. This study aimed to assess the pharmacological effects of taurine (intracerebroventricular; i.c.v.) on ethanol intake/preference of rats either control (i.e., alcohol naïve) or forced ethanol intake (since juvenile age with a chronic intermittent access model). In addition, to explore anxiety-like behavior (through defensive burying behavior test) as pharmacological control of taurine. We found that acute (i.c.v.) taurine reduced alcohol consumption, i.e., taurine significantly decreased both alcohol intake and preference in adult male Wistar rats. Moreover, taurine elicits an anxiolytic-like effect in all administered groups independently of previous alcohol exposure.


Assuntos
Alcoolismo , Taurina , Humanos , Ratos , Animais , Masculino , Taurina/farmacologia , Ratos Wistar , Etanol/farmacologia , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Mamíferos
14.
Pancreas ; 53(4): e301-e309, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38373081

RESUMO

OBJECTIVE: A significant number of patients experience early recurrence after surgical resection for pancreatic ductal adenocarcinoma (PDAC), negating the benefit of surgery. The present study conducted clinicopathologic and metabolomic analyses to explore the factors associated with the early recurrence of PDAC. MATERIALS AND METHODS: Patients who underwent pancreatectomy for PDAC at Kagawa University Hospital between 2011 and 2020 were enrolled. Tissue samples of PDAC and nonneoplastic pancreas were collected and frozen immediately after resection. Charged metabolites were quantified by capillary electrophoresis-mass spectrometry. Patients who relapsed within 1 year were defined as the early recurrence group. RESULTS: Frozen tumor tissue and nonneoplastic pancreas were collected from 79 patients. The clinicopathologic analysis identified 11 predictive factors, including preoperative carbohydrate antigen 19-9 levels. The metabolomic analysis revealed that only hypotaurine was a significant risk factor for early recurrence. A multivariate analysis, including clinical and metabolic factors, showed that carbohydrate antigen 19-9 and hypotaurine were independent risk factors for early recurrence ( P = 0.045 and P = 0.049, respectively). The recurrence-free survival rate 1 year after surgery with both risk factors was only 25%. CONCLUSIONS: Our results suggested that tumor hypotaurine is a potential metabolite associated with early recurrence. Carbohydrate antigen 19-9 and hypotaurine showed a vital utility for predicting early recurrence.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Taurina/análogos & derivados , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Pancreatectomia/métodos , Carboidratos , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Antígeno CA-19-9
15.
Cryobiology ; 114: 104858, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346570

RESUMO

Cryopreservation consist of a set of methods to preserve cells and tissues by drastically reducing the temperature. Among some undesired effects, cryopreservation might generate reactive oxygen species that lead to an increase of oxidative stress, causing damage to cells. This study aimed to test taurine, cysteine, and melatonin on the freezing of Prochilodus brevis sperm and assess its effects on post-thawed sperm quality. Sperm was collected and seven pools were formed (n = 7). They were diluted (1:9) in standard medium (5% glucose, 10% dimethyl sulfoxide and 5% egg yolk) supplemented or not (control) with taurine (0.3, 1.0, 3.16 or 10.0 mM), cysteine (0.3, 1.0, 3.16 or 10.0 mM) or melatonin (0.6, 1.12, 2.0 or 3.56 mM). Post-thawed sperm was evaluated for kinetic (total motility, velocities, and percentage of rapid cells), morphology and membrane and DNA integrity. Differences were found when melatonin was used as an antioxidant. For the variables rapid sperm and sperm velocities, 3.56 mM melatonin presented higher results than the control (melatonin 0 mM). Melatonin 2 mM was similar to 3.56 mM on rapid sperm, average path velocity (VAP) and curvilinear velocity (VCL). No difference was found between concentration 0 mM (control) and taurine treatments. As for cysteine, 0.3 mM presented the best results for rapid sperm than 10 mM, and higher VCL and VAP than 1 mM. Melatonin 3.56 mM presented higher results on kinetic parameters (rapid motility, VCL, VSL and VAP) than other tested antioxidants. Therefore, melatonin 3.56 mM is recommended to be added to the sperm freezing medium of P. brevis.


Assuntos
Caraciformes , Melatonina , Preservação do Sêmen , Animais , Masculino , Congelamento , Antioxidantes/farmacologia , Melatonina/farmacologia , Criopreservação/métodos , Cisteína/farmacologia , Taurina/farmacologia , Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Glucose/farmacologia
16.
Drug Des Devel Ther ; 18: 133-159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283137

RESUMO

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 µM, hBuChE: IC50 = 0.43 µM) and MAOs (hMAO-A: IC50 = 2.30 µM, hMAO-B: IC50 = 4.75 µM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Taurina/análogos & derivados , Camundongos , Animais , Tacrina/farmacologia , Tacrina/química , Tacrina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Colinesterases/metabolismo , Selegilina/farmacologia , Selegilina/uso terapêutico , Monoaminoxidase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Doenças Neurodegenerativas/tratamento farmacológico , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/química , Acetilcolinesterase/metabolismo , Desenho de Fármacos , Relação Estrutura-Atividade , Peptídeos beta-Amiloides
17.
Sci Total Environ ; 915: 169897, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38184250

RESUMO

pH treatment promotes single-cell lipid accumulation and significantly affects microalgae growth. This study investigates the correlation between lipid content and environmental pH using the model diatom Phaeodactylum tricornutum (P. tricornutum). We compared three distinct pH treatment strategies-continuous, intermittent, and a two-phase culture-in P. tricornutum. Rigorous analysis of chlorophyll content, cell density, and lipid content indicated that ongoing pH treatment at pH 9.5 (CHES) emerged as the most effective approach for lipid accumulation in P. tricornutum. The CHES buffer treatment significantly boosted total lipid yield and led to a reduction in protein content. Carbohydrate content experienced a slight decline under CHES buffer treatment, but changes were observed in the activities of key enzymes. Specifically, [acyl-carrier-protein] S-malonyltransferase (MAT) activity decreased after 3 days in the control treatment, while no significant change was noted under the CHES buffer treatment. In contrast, diacylglycerol O-acyltransferase (DGAT) activity showed upregulation 2 and 3 days post-CHES buffer treatment. Moreover, the study identified differentially expressed genes enriched in Gene Ontology (GO) terms associated with protein biosynthesis, photosynthesis, nucleoside metabolism, and transferase activity. These outcomes underscore the pivotal role of CHES buffer in orchestrating primary metabolism, potentially steering carbon flux towards lipogenesis. As a result, the potential of microalgae as a sustainable source of biofuels contributes significantly to the transition towards a more environmentally friendly energy landscape.


Assuntos
Diatomáceas , Taurina/análogos & derivados , Fotossíntese , Lipídeos , Concentração de Íons de Hidrogênio
18.
Int Immunopharmacol ; 128: 111527, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38215655

RESUMO

To predict early remission following anti-integrin therapy (vedolizumab [VDZ]) in patients with moderate-to-severe active ulcerative colitis (UC) using non-invasive biomarkers. The clinical data of a cohort of 33 patients with moderate-to-severe active UC admitted to the Department of Gastroenterology at Suzhou Municipal Hospital between January 2021 and December 2022 were collected. Of these, 9 patients declined VDZ treatment, and 21 received VDZ at doses of 300 mg weeks 0, 2, and 6, each administered within a 30-minute infusion period. The treatment regimen aimed to induce remission of clinical symptoms; hence, the same dose was administered every 8 weeks. At weeks 0 and 14, serum C-reactive protein (CRP) and erythrocyte sedimentation rate were measured using a modified Mayo score. In addition to clinical assessment, stool samples at baseline and weeks 14 were collected and evaluated using 16SrRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS). Clinical remission was determined based on the clinical symptoms and partial Mayo scores. In patients who received VDZ, the strains of bifidobacterium longum (P = 0.022) and bacteroides sartorii (P = 0.039) significantly increased after treatment than before treatment. GC-MS analysis showed that taurine (P = 0.047) and putrescine (P = 0.035) significantly decreased after treatment. Furthermore, while acetamide exhibited a notable increase (P = 0.001), arachidic acid (P < 0.001) and behenic acid (P = 0.005) demonstrated statistically significant elevations. The combined prediction model of acetamide, taurine, and putrescine demonstrated a high predictive value of early remission in patients with moderate-to-severe active UC following VDZ treatment (area under the curve = 0.911, P = 0.014).


Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Humanos , Colite Ulcerativa/tratamento farmacológico , Putrescina/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Resultado do Tratamento , Indução de Remissão , Acetamidas , Taurina , Estudos Retrospectivos
19.
Acta Physiol (Oxf) ; 240(3): e14101, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38243723

RESUMO

AIM: Despite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet ß-cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into ß-cells and its acute and chronic intracellular interactions. METHODS: The molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 ß-cells and primary mouse and human islets to a range of the homologs of the amino acid (assayed at 2-20 mM), using the hormone release and imaging of intracellular signals as surrogate read-outs. Known secretagogues were employed to profile the interaction of taurine with acute and chronic intracellular signals. RESULTS: Taurine transporter TauT was expressed in the islet ß-cells, with the transport of taurine and homologs having a weak sulfonate specificity but significant sensitivity to the molecular weight of the transporter. Taurine, hypotaurine, homotaurine, and ß-alanine enhanced insulin secretion in a glucose-dependent manner, an action potentiated by cytosolic Ca2+ and cAMP. Acute and chronic ß-cell insulinotropic effects of taurine were highly sensitive to co-agonism with GLP-1, forskolin, tolbutamide, and membrane depolarization, with an unanticipated indifference to the activation of PKC and CCK8 receptors. Pre-culturing with GLP-1 or KATP channel inhibitors sensitized or, respectively, desensitized ß-cells to the acute taurine stimulus. CONCLUSION: Together, these data demonstrate the pathways whereby taurine exhibits a range of beneficial effects on insulin secretion and ß-cell function, consistent with the antidiabetic potential of its dietary low-dose supplementation.


Assuntos
Células Secretoras de Insulina , Ilhotas Pancreáticas , Humanos , Animais , Camundongos , Taurina/farmacologia , Transdução de Sinais , Peptídeo 1 Semelhante ao Glucagon , Hipoglicemiantes
20.
Brain Dev ; 46(4): 180-186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38171994

RESUMO

OBJECTIVE: The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics. METHODS: This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS). RESULTS: We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups. CONCLUSIONS: Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.


Assuntos
Epilepsia , Espectrometria de Massas em Tandem , Humanos , Criança , Pré-Escolar , Estudos Prospectivos , Metaboloma , Epilepsia/diagnóstico , Convulsões , Taurina , Biomarcadores
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