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1.
Sci Total Environ ; 923: 171450, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38438028

RESUMO

Delafloxacin (DFX), one of the latest additions to the fluoroquinolone antibiotics, is gaining heightened recognition in human therapy due to its potential antibacterial efficacy in a wide range of applications. Concerns have arisen regarding its presence in the environment and its potential interactions with multivalent metals, such as calcium (Ca). The present study investigated the trans- and multigenerational effects of environmentally projected concentrations of DFX (100-400 µg DFX L-1) on individual- and population-level responses of parental S. vetulus (F0) and its descendants (F1) under normal (26 mg L-1) and high (78 mg L-1) Ca conditions. Exposure of the F0 generation to DFX under the normal Ca condition resulted in reduced juvenile body length (JBL), increased age-specific survival rate (lx), indicating prolonged developmental time, reduced age-specific fecundity rate (mx), and decreased population growth rate (rm). Under the high Ca condition, JBL, mx, and rm were adversely affected. Transgenerational effects of DFX existed, as F1 individuals exhibited persistent suppressions in at least one endpoint under both Ca conditions even after being transferred to a clear medium. Continuous exposure of the F1 generation to DFX had negative impacts on JBL, mx, and rm under the normal Ca condition, and on JBL and rm under the high Ca condition. However, cumulative effects were not observed, suggesting the potential development of tolerance to DFX in the F1 organisms. These findings suggest that DFX is a harmful compound for the non-target model organism S. vetulus and reveal a potential antagonism between DFX and Ca. Nevertheless, the interaction between other (fluoro)quinolones and Ca remains unclear, necessitating further research to establish this phenomenon more comprehensively, including understanding the interaction mechanism in ecotoxicological contexts.


Assuntos
Cladóceros , Poluentes Químicos da Água , Humanos , Animais , Cálcio , Fluoroquinolonas/toxicidade , Antibacterianos/toxicidade , Poluentes Químicos da Água/toxicidade
2.
Sci Total Environ ; 923: 171398, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442753

RESUMO

Methylmercury (MeHg), as a global environmental pollutant, is of concern globally due to its neurodevelopmental toxicity. Mitochondria-associated membranes (MAMs) are highly dynamic sites of endoplasmic reticulum (ER)-haemocyte contact. MAMs are closely associated with the pathophysiology of neurological disorders due to their role in the transfer of calcium ions (Ca2+) between mitochondria and the ER. However, the molecular mechanisms that control these interactions in MeHg-induced neurotoxicity have not yet been characterized. In the current study, MeHg caused increases in the levels of both cytosolic and mitochondrial Ca2+ in PC12 cells and promoted MAMs formation in both in vivo and in vitro experiments. Of note, MeHg perturbed mitochondrial dynamics, promoting a shift toward a fission phenotype, and this was supported by the dysregulation of fission regulators. Interestingly, the MeHg-induced promotion of MAMs formation and increase in Ca2+ levels were effectively attenuated by the inhibition of mitochondrial fission using Mdivi-1, a DRP1 inhibitor. Furthermore, MeHg triggered the AMPK pathway, and most of the aforementioned changes were significantly rescued by Compound C. Mechanistic investigations revealed a reciprocal relationship between AMPK- and Ca2+-mediated mitochondrial fission. The specific inhibitor of Ca2+ uniporter, ruthenium-red (RuR), effectively abolished the feedback regulation of mitochondrial dynamics and MAMs formation mediated by AMPK in response to MeHg-induced Ca2+ overload. This study reveals a novel role of AMPK-DRP1-mediated mitochondrial fragmentation in the coupling of ER-mitochondrial calcium microdomains in MeHg-induced neurotoxicity. The findings provide valuable insights for the development of strategies to regulate mitochondrial imbalances in neurological diseases.


Assuntos
Cálcio , Compostos de Metilmercúrio , Ratos , Animais , Cálcio/metabolismo , Dinâmica Mitocondrial , Compostos de Metilmercúrio/toxicidade , Compostos de Metilmercúrio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Mitocôndrias , Retículo Endoplasmático/metabolismo , Homeostase
3.
Neural Comput ; 36(4): 645-676, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38457763

RESUMO

The motility of microglia involves intracellular signaling pathways that are predominantly controlled by changes in cytosolic Ca2+ and activation of PI3K/Akt (phosphoinositide-3-kinase/protein kinase B). In this letter, we develop a novel biophysical model for cytosolic Ca2+ activation of the PI3K/Akt pathway in microglia where Ca2+ influx is mediated by both P2Y purinergic receptors (P2YR) and P2X purinergic receptors (P2XR). The model parameters are estimated by employing optimization techniques to fit the model to phosphorylated Akt (pAkt) experimental modeling/in vitro data. The integrated model supports the hypothesis that Ca2+ influx via P2YR and P2XR can explain the experimentally reported biphasic transient responses in measuring pAkt levels. Our predictions reveal new quantitative insights into P2Rs on how they regulate Ca2+ and Akt in terms of physiological interactions and transient responses. It is shown that the upregulation of P2X receptors through a repetitive application of agonist results in a continual increase in the baseline [Ca2+], which causes the biphasic response to become a monophasic response which prolongs elevated levels of pAkt.


Assuntos
Microglia , Proteínas Proto-Oncogênicas c-akt , Microglia/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Receptores Purinérgicos/metabolismo
4.
PLoS Genet ; 20(3): e1011186, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483976

RESUMO

Egg activation, representing the critical oocyte-to-embryo transition, provokes meiosis completion, modification of the vitelline membrane to prevent polyspermy, and translation of maternally provided mRNAs. This transition is triggered by a calcium signal induced by spermatozoon fertilization in most animal species, but not in insects. In Drosophila melanogaster, mature oocytes remain arrested at metaphase-I of meiosis and the calcium-dependent activation occurs while the oocyte moves through the genital tract. Here, we discovered that the oenocytes of fruitfly females are required for egg activation. Oenocytes, cells specialized in lipid-metabolism, are located beneath the abdominal cuticle. In adult flies, they synthesize the fatty acids (FAs) that are the precursors of cuticular hydrocarbons (CHCs), including pheromones. The oenocyte-targeted knockdown of a set of FA-anabolic enzymes, involved in very-long-chain fatty acid (VLCFA) synthesis, leads to a defect in egg activation. Given that some but not all of the identified enzymes are required for CHC/pheromone biogenesis, this putative VLCFA-dependent remote control may rely on an as-yet unidentified CHC or may function in parallel to CHC biogenesis. Additionally, we discovered that the most posterior ventral oenocyte cluster is in close proximity to the uterus. Since oocytes dissected from females deficient in this FA-anabolic pathway can be activated in vitro, this regulatory loop likely operates upstream of the calcium trigger. To our knowledge, our findings provide the first evidence that a physiological extra-genital signal remotely controls egg activation. Moreover, our study highlights a potential metabolic link between pheromone-mediated partner recognition and egg activation.


Assuntos
Drosophila melanogaster , Drosophila , Animais , Feminino , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Cálcio/metabolismo , Fertilização , Oócitos/metabolismo , Feromônios/genética , Feromônios/metabolismo
5.
Protein Sci ; 33(4): e4960, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38501502

RESUMO

Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is a multidomain serine/threonine kinase that plays important roles in the brain, heart, muscle tissue, and eggs/sperm. The N-terminal kinase and regulatory domain is connected by a flexible linker to the C-terminal hub domain. The hub domain drives the oligomeric organization of CaMKII, assembling the kinase domains into high local concentration. Previous structural studies have shown multiple stoichiometries of the holoenzyme as well as the hub domain alone. Here, we report a comprehensive study of the hub domain stoichiometry and stability in solution. We solved two crystal structures of the CaMKIIß hub domain that show 14-mer (3.1 Å) and 16-mer (3.4 Å) assemblies. Both crystal structures were determined from crystals grown in the same drop, which suggests that CaMKII oligomers with different stoichiometries likely coexist. To further interrogate hub stability, we employed mass photometry and temperature denaturation studies of CaMKIIß and CaMKIIα hubs, which highlight major differences between these highly similar domains. We created a dimeric CaMKIIß hub unit using rational mutagenesis, which is significantly less stable than the oligomer. Both hub domains populate an intermediate during unfolding. We found that multiple CaMKIIß hub stoichiometries are present in solution and that larger oligomers are more stable. CaMKIIα had a narrower distribution of molecular weight and was distinctly more stable than CaMKIIß.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Cálcio , Masculino , Humanos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Sêmen/metabolismo
6.
Turk J Pediatr ; 66(1): 75-80, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523381

RESUMO

BACKGROUND: Overdose with calcium-channel blockers (CCBs) still maintain their importance with a high lethality rate after exposure. We report the intravenous lipid emulsion therapy (ILE) therapy in our CCB overdose patients. METHODS: We retrospectively analyzed the records of 6 patients with CCB intoxication from Batman Training and Research Hospital PICU between March 2021 and September 2022. Patients aged 0-18 years who received ILE treatment for CCB poisoning were included. RESULTS: All six patients ingested CCB with the intention of committing suicide and were followed up in the pediatric intensive care unit (PICU). All patients received ILE therapy due to hemodynamic instability despite intravenous fluid boluses, calcium, glucagon, insulin-dextrose, and vasoactive agents. Vasoactive-Inotropic Score (VIS) decreased after ILE treatment. All patients were transferred from the PICU after recovery. CONCLUSIONS: ILE therapy should be kept in mind as a salvage therapy in hemodynamically unstable CCB poisoning cases that do not respond to initial and advanced options.


Assuntos
Bloqueadores dos Canais de Cálcio , Overdose de Drogas , Humanos , Criança , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cálcio/uso terapêutico , Estudos Retrospectivos , Estado Terminal/terapia , Overdose de Drogas/tratamento farmacológico , Lipídeos/uso terapêutico
7.
Channels (Austin) ; 18(1): 2325032, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38445990

RESUMO

Ion channels play key roles in human physiology and are important targets in drug discovery. The atomic-scale structures of ion channels provide invaluable insights into a fundamental understanding of the molecular mechanisms of channel gating and modulation. Recent breakthroughs in deep learning-based computational methods, such as AlphaFold, RoseTTAFold, and ESMFold have transformed research in protein structure prediction and design. We review the application of AlphaFold, RoseTTAFold, and ESMFold to structural modeling of ion channels using representative voltage-gated ion channels, including human voltage-gated sodium (NaV) channel - NaV1.8, human voltage-gated calcium (CaV) channel - CaV1.1, and human voltage-gated potassium (KV) channel - KV1.3. We compared AlphaFold, RoseTTAFold, and ESMFold structural models of NaV1.8, CaV1.1, and KV1.3 with corresponding cryo-EM structures to assess details of their similarities and differences. Our findings shed light on the strengths and limitations of the current state-of-the-art deep learning-based computational methods for modeling ion channel structures, offering valuable insights to guide their future applications for ion channel research.


Assuntos
Cálcio , Canais Iônicos , Humanos , Potássio
8.
Sci Rep ; 14(1): 6751, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514795

RESUMO

Mitochondrial Ca2+ overload can mediate mitochondria-dependent cell death, a major contributor to several human diseases. Indeed, Duchenne muscular dystrophy (MD) is driven by dysfunctional Ca2+ influx across the sarcolemma that causes mitochondrial Ca2+ overload, organelle rupture, and muscle necrosis. The mitochondrial Ca2+ uniporter (MCU) complex is the primary characterized mechanism for acute mitochondrial Ca2+ uptake. One strategy for preventing mitochondrial Ca2+ overload is deletion of the Mcu gene, the pore forming subunit of the MCU-complex. Conversely, enhanced MCU-complex Ca2+ uptake is achieved by deleting the inhibitory Mcub gene. Here we show that myofiber-specific Mcu deletion was not protective in a mouse model of Duchenne MD. Specifically, Mcu gene deletion did not reduce muscle histopathology, did not improve muscle function, and did not prevent mitochondrial Ca2+ overload. Moreover, myofiber specific Mcub gene deletion did not augment Duchenne MD muscle pathology. Interestingly, we observed MCU-independent Ca2+ uptake in dystrophic mitochondria that was sufficient to drive mitochondrial permeability transition pore (MPTP) activation and skeletal muscle necrosis, and this same type of activity was observed in heart, liver, and brain mitochondria. These results demonstrate that mitochondria possess an uncharacterized MCU-independent Ca2+ uptake mechanism that is sufficient to drive MPTP-dependent necrosis in MD in vivo.


Assuntos
Distrofia Muscular de Duchenne , Animais , Humanos , Camundongos , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Morte Celular , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Distrofia Muscular de Duchenne/patologia , Necrose/metabolismo
9.
Opt Express ; 32(4): 5429-5443, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439270

RESUMO

Brilliant colors in nature arise from the interference of light with periodic nanostructures resulting in structural color. While such biological photonic structures have long attracted interest in insects and plants, they are little known in other groups of organisms. Unexpected in the kingdom of Amoebozoa, which assembles unicellular organisms, structural colors were observed in myxomycetes, an evolutionary group of amoebae forming macroscopic, fungal-like structures. Previous work related the sparkling appearance of Diachea leucopodia to thin film interference. Using optical and ultrastructural characterization, we here investigated the occurrence of structural color across 22 species representing two major evolutionary clades of myxomycetes including 14 genera. All investigated species showed thin film interference at the peridium, producing colors with hues distributed throughout the visible range that were altered by pigmentary absorption. A white reflective layer of densely packed calcium-rich shells is observed in a compound peridium in Metatrichia vesparium, whose formation and function are still unknown. These results raise interesting questions on the biological relevance of thin film structural colors in myxomycetes, suggesting they may be a by-product of their reproductive cycle.


Assuntos
Amebozoários , Mixomicetos , Nanoestruturas , Cálcio , Fótons
10.
11.
Radiology ; 310(3): e231557, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38441097

RESUMO

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Cálcio , Doença da Artéria Coronariana/diagnóstico por imagem , Dor no Peito/diagnóstico por imagem
12.
Wei Sheng Yan Jiu ; 53(1): 81-87, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38443177

RESUMO

OBJECTIVE: To explore the protective effect of different ratios of galactose oligosaccharide(GOS) and polydextrose(PDX) on intestinal cell barrier damage model of Caco-2. METHODS: The same batch of Caco-2 cells were cultured to form a cell barrier model and randomly divided into damaged model group without calcium, calcium-containing blank control group(1.8 mmol/L Ca~(2+)), low-ratio/low-dose group(1.8 mmol/L Ca~(2+)+2 mg/mL GOS+2 mg/mL PDX) and low-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+4 mg/mL GOS+4 mg/mL PDX), low-ratio/high-dose group(1.8 mmol/L Ca~(2+)+8 mg/mL GOS+8 mg/mL PDX) and high-ratio/low-dose group(1.8 mmol/L Ca~(2+)+0.8 mg/mL GOS+3.2mg/mL PDX), high-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+1.6 mg/mL GOS+6.4 mg/mL PDX), high-ratio/high-dose group(1.8 mmol/L Ca~(2+)+3.2mg/mL GOS+12.8 mg/mL PDX), a total of 8 groups, three parallel groups were performed in each group. The Trans Epithelial Electrical Resistance value and apparent permeability coefficient value of each group were determined after 4 d culture, and the morphology of tight junction proteins ZO-1, Occludin and Claudin-1 were observed by immunofluorescence method, and the expression levels of inflammatory related factors in each group were determined by protein microarray method. RESULTS: Compared with damaged model group, TEER ratio in calcium-containing blank control group was significantly increased(P<0.05), while Papp value was significantly decreased(P<0.05);Compared with calcium-containing blank control group, TEER ratio in low-ratio/medium-dose group and high-ratio/high-dose group was significantly increased(P<0.05) while Papp value was significantly decreased(P<0.05), and they could significantly down-regulate some inflammatory response related cytokines. The cell barrier was intact in all groups except for the compact junction protein structure in the model group. CONCLUSION: Compared with Ca~(2+) alone, the combination of two prebiotics can enhance the density of Caco-2 cell barrier and reduced the permeability of cell bypass. And it can significantly reduce the expression level of some inflammatory cytokines and effectively protect the intestinal cell barrier.


Assuntos
Cálcio da Dieta , Cálcio , Glucanos , Humanos , Células CACO-2 , Citocinas , Oligossacarídeos/farmacologia
13.
Rev Med Suisse ; 20(864): 500-504, 2024 Mar 06.
Artigo em Francês | MEDLINE | ID: mdl-38445680

RESUMO

The coronary artery calcium score (CAC-score) using imaging is a cardiovascular screening tool that can be used in adults with no known cardiovascular disease and no symptoms suggestive of a cardiovascular pathology. It involves calculating the amount of calcification in the coronary arteries on a low-dose, non-injected chest CT-scan. A positive score above 0 is associated with more cardiovascular events. The CAC-score is currently selectively recommended for certain adults at intermediate cardiovascular risk, when the introduction of lipid-lowering treatment or the intensification of preventive measures remain uncertain.


Le score calcique coronarien (CAC-score) utilisant l'imagerie est un outil de dépistage cardiovasculaire utilisable chez des adultes sans maladie cardiovasculaire connue et symptômes évoquant une pathologie cardiovasculaire. Il s'agit d'un calcul de la quantité de calcifications dans les artères coronaires lors d'un CT-scan thoracique non injecté à faible dose. Un score positif au-dessus de 0 est associé avec plus d'événements cardiovasculaires. Le CAC-score est actuellement recommandé sélectivement chez certains adultes à risque cardiovasculaire intermédiaire, lorsque l'introduction d'un traitement hypolipémiant ou l'intensification des mesures de prévention restent incertaines.


Assuntos
Doenças Cardiovasculares , Adulto , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Cálcio , Vasos Coronários/diagnóstico por imagem , Fatores de Risco , Fatores de Risco de Doenças Cardíacas
14.
J Gen Physiol ; 156(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38445312

RESUMO

RYR1 is the most commonly mutated gene associated with congenital myopathies, a group of early-onset neuromuscular conditions of variable severity. The functional effects of a number of dominant RYR1 mutations have been established; however, for recessive mutations, these effects may depend on multiple factors, such as the formation of a hypomorphic allele, or on whether they are homozygous or compound heterozygous. Here, we functionally characterize a new transgenic mouse model knocked-in for mutations identified in a severely affected child born preterm and presenting limited limb movement. The child carried the homozygous c.14928C>G RYR1 mutation, resulting in the p.F4976L substitution. In vivo and ex vivo assays revealed that homozygous mice fatigued sooner and their muscles generated significantly less force compared with their WT or heterozygous littermates. Electron microscopy, biochemical, and physiological analyses showed that muscles from RyR1 p.F4976L homozygous mice have the following properties: (1) contain fewer calcium release units and show areas of myofibrillar degeneration, (2) contain less RyR1 protein, (3) fibers show smaller electrically evoked calcium transients, and (4) their SR has smaller calcium stores. In addition, single-channel recordings indicate that RyR1 p.F4976L exhibits higher Po in the presence of 100 µM [Ca2+]. Our mouse model partly recapitulates the clinical picture of the homozygous human patient and provides significant insight into the functional impact of this mutation. These results will help understand the pathology of patients with similar RYR1 mutations.


Assuntos
Cálcio , Doenças Musculares , Animais , Criança , Humanos , Camundongos , Modelos Animais de Doenças , Homeostase , Camundongos Transgênicos , Músculos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética
15.
Sci Adv ; 10(10): eadk2298, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38446885

RESUMO

Adoptive T cell therapies rely on the production of T cells with an antigen receptor that directs their specificity toward tumor-specific antigens. Methods for identifying relevant T cell receptor (TCR) sequences, predominantly achieved through the enrichment of antigen-specific T cells, represent a major bottleneck in the production of TCR-engineered cell therapies. Fluctuation of intracellular calcium is a proximal readout of TCR signaling and candidate marker for antigen-specific T cell identification that does not require T cell expansion; however, calcium fluctuations downstream of TCR engagement are highly variable. We propose that machine learning algorithms may allow for T cell classification from complex datasets such as polyclonal T cell signaling events. Using deep learning tools, we demonstrate accurate prediction of TCR-transgenic CD8+ T cell activation based on calcium fluctuations and test the algorithm against T cells bearing a distinct TCR as well as polyclonal T cells. This provides the foundation for an antigen-specific TCR sequence identification pipeline for adoptive T cell therapies.


Assuntos
Algoritmos , Cálcio , Animais , Animais Geneticamente Modificados , Aprendizado de Máquina , Receptores de Antígenos de Linfócitos T
16.
Chem Pharm Bull (Tokyo) ; 72(3): 286-293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447973

RESUMO

To explore drug interactions involving sodium zirconium cyclosilicate hydrate (SZC) and concomitant drugs like calcium antagonists (amlodipine and nifedipine) and ß-blockers (carvedilol and bisoprolol), we investigate how these concomitant drugs influenced the administration of SZC in an artificial intestinal juice. Initially, we assessed the potassium ion adsorption capacity, ranking it as follows: calcium polystyrene sulfonate (CPS, 54.9 mg/g) < sodium polystyrene sulfonate (SPS, 62.1 mg/g) < SZC (90.8 mg/g). However, the adsorption equilibrium was achieved in the order of CPS ≒ SPS (within 1 min) < SZC (within 1 h). Subsequently, we determined the residual percentages of amlodipine, nifedipine, carvedilol, and bisoprolol, finding them to be 79.0-91.9% for SZC, 0.38-38.4% for SPS, and 0.57-29.0% for CPS. These results suggest the efficacy of SZC in managing hyperkalemia alongside concomitant drugs in an artificial intestinal juice, with particular emphasis on amlodipine (calcium antagonist) and carvedilol (ß-blocker). Additionally, we identified the presence of carbon, nitrogen, and oxygen components from both drugs on the SZC surface following interaction. We also evaluated how amlodipine, nifedipine, carvedilol, and bisoprolol affected the administration of SZC in the presence of potassium ions. Our results indicate that potassium ions and concomitant drugs did not interfere with each other in the artificial intestinal juice. These results offer valuable insights into the administration of SZC in conjunction with concomitant drugs. Lastly, the presented data shows qualitative results in this study.


Assuntos
Bisoprolol , Nifedipino , Poliestirenos , Silicatos , Preparações Farmacêuticas , Carvedilol , Cálcio , Anlodipino , Íons , Potássio
17.
Biol Pharm Bull ; 47(3): 591-599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447991

RESUMO

The pain matrix, which includes several brain regions that respond to pain sensation, contribute to the development of chronic pain. Thus, it is essential to understand the mechanism of causing chronic pain in the pain matrix such as anterior cingulate (ACC), or primary somatosensory (S1) cortex. Recently, combined experiment with the behavior tests and in vivo calcium imaging using fiber photometry revealed the interaction between the neuronal function in deep brain regions of the pain matrix including ACC and the phenotype of chronic pain. However, it remains unclear whether this combined experiment can identify the interaction between neuronal activity in S1, which receive pain sensation, and pain behaviors such as hyperalgesia or allodynia. In this study, to examine whether the interaction between change of neuronal activity in S1 and hyperalgesia in hind paw before and after causing inflammatory pain was detected from same animal, the combined experiment of in vivo fiber photometry system and von Frey hairs test was applied. This combined experiment detected that amplitude of calcium responses in S1 neurons increased and the mechanical threshold of hind paw decreased from same animals which have an inflammatory pain. Moreover, we found that the values between amplitude of calcium responses and mechanical thresholds were shifted to negative correlation after causing inflammatory pain. Thus, the combined experiment with fiber photometry and the behavior tests has a possibility that can simultaneously consider the interaction between neuronal activity in pain matrix and pain induced behaviors and the effects of analgesics or pain treatments.


Assuntos
Dor Crônica , Hiperalgesia , Animais , Camundongos , Escala de Avaliação Comportamental , Cálcio , Córtex Somatossensorial , Cálcio da Dieta , Modelos Animais de Doenças , Neurônios , Fotometria
18.
J Health Popul Nutr ; 43(1): 38, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38449003

RESUMO

BACKGROUND: There have been studies on the relationship between hepatitis B virus (HBV) infection and diet. We hypothesized HBV infection is related to dietary calcium intake, but the evidence is limited. This study aimed to examine whether dietary calcium intake is independently related to HBV infection in the United States population. METHODS: A total of 20,488 participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES), conducted from 2007 to 2020, were included in this study. Pearson correlation was used to test the association between dietary calcium and serum calcium. The relationships of HBV infection with dietary calcium and serum calcium were assessed by logistic regression models. RESULTS: There was a weak correlation between dietary calcium and serum calcium (r = 0.048). Logistic regression models indicated that HBV infection had a linear negative correlation with dietary calcium (OR 0.37; 95%CI 0.19, 0.76). For each additional 10 mg dietary calcium, the possibility of HBV infection was reduced by 63%. Hepatitis B positive participants had lower serum calcium content than negative participants. Stratified analysis shown the linear relationship between calcium and HBV infection varied among sex, race/ethnicity, and body mass index. CONCLUSION: Our findings demonstrated HBV infection was linearly and inversely correlated with dietary calcium. The current study is expected to offer a fresh perspective on reducing HBV infection.


Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Adulto , Cálcio da Dieta , Inquéritos Nutricionais , Cálcio , Hepatite B/epidemiologia
19.
Pediatr Dent ; 46(1): 13-26, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449041

RESUMO

Purpose: The purpose of this study was to present an evidence-based guideline for primary teeth with deep caries or trauma requiring vital pulp therapies (VPT). Methods: A systematic review/meta-analysis on vital primary teeth resulting from trauma or caries was conducted using GRADE to assess the certainty of evidence for clinical recommendations. A decision tree was provided for choosing VPTs. Results: No articles on trauma VPT were found. For VPT in primary teeth with deep caries, indirect pulp treatment (IPT) or pulpotomy using the calcium silicate cement (mineral trioxide aggregate [MTA] or Biodentine®) show increased success over using direct pulp capping (DPC) and other pulpotomies. Different liners do not affect IPT success (high certainty) or DPC capping agents' success (very low certainty) after 24 months. It is strongly recommended, with high certainty from 24-month data, that calcium silicate cement pulpotomy is preferred over formocresol, ferric sulfate, zinc oxide eugenol pulpotomy, and other pulpotomies. Using selective caries removal and IPT for deep caries is strongly recommended with moderate certainty over complete and stepwise removal. Statistically, this results in significantly fewer pulp exposures. No caries removal and Hall technique crown may be used when indicated (moderate certainty at 24 months). For vital primary incisors with deep caries, pulpotomy was significantly better statistically than pulpectomy. Teeth diagnosed with/without reversible pulpitis pain showed comparable success after 12 months of treatment by IPT or calcium silicate cement pulpotomy. The following had little or no significant effect on MTA pulpotomy success: coronal pulp removal methods; irrigation solution; method to control hemorrhage; base over MTA; treatment in one or two visits; anterior or posterior teeth. Conclusions: Indirect pulp treatment or calcium silicate cement pulpotomy is likely to increase vital pulp therapy success over other VPTs such as direct pulp capping and other pulpotomies after 24 months (moderate certainty).


Assuntos
Compostos de Cálcio , Assistência Odontológica , Pulpotomia , Silicatos , Humanos , Polpa Dentária , Cálcio , Cimentos Dentários , Cimentos de Ionômeros de Vidro , Dente Decíduo
20.
PLoS One ; 19(3): e0299042, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427657

RESUMO

Epigallocatechin gallate (EGCG) is a polyphenolic component of green tea that has anti-oxidative and anti-inflammatory effects in neurons. Ischemic stroke is a major neurological disease that causes irreversible brain disorders. It increases the intracellular calcium concentration and induces apoptosis. The regulation of intracellular calcium concentration is important to maintain the function of the nervous system. Hippocalcin is a neuronal calcium sensor protein that controls intracellular calcium concentration. We investigated whether EGCG treatment regulates the expression of hippocalcin in stroke animal model and glutamate-induced neuronal damage. We performed middle cerebral artery occlusion (MCAO) to induce cerebral ischemia. EGCG (50 mg/kg) or phosphate buffered saline was injected into the abdominal cavity just before MCAO surgery. The neurobehavioral tests were performed 24 h after MCAO surgery and cerebral cortex tissue was collected. MCAO damage induced severe neurobehavioral disorders, increased infarct volume, and decreased the expression of hippocalcin in the cerebral cortex. However, EGCG treatment improved these deficits and alleviated the decrease in hippocalcin expression in cerebral cortex. In addition, EGCG dose-dependently alleviated neuronal cell death and intracellular calcium overload in glutamate-exposed neurons. Glutamate exposure reduced hippocalcin expression, decreased Bcl-2 expression, and increased Bax expression. However, EGCG treatment mitigated these changes caused by glutamate toxicity. EGCG also attenuated the increase in caspase-3 and cleaved caspase-3 expressions caused by glutamate exposure. The effect of EGCG was more pronounced in non-transfected cells than in hippocalcin siRNA-transfected cells. These findings demonstrate that EGCG protects neurons against glutamate toxicity through the regulation of Bcl-2 family proteins and caspase-3. It is known that hippocalcin exerts anti-apoptotic effect through the modulation of apoptotic pathway. Thus, we can suggest evidence that EGCG has a neuroprotective effect by regulating hippocalcin expression in ischemic brain damage and glutamate-exposed cells.


Assuntos
Catequina , AVC Isquêmico , Fármacos Neuroprotetores , Animais , Apoptose , Cálcio/metabolismo , Caspase 3/metabolismo , Catequina/análogos & derivados , Ácido Glutâmico/metabolismo , Hipocalcina/genética , Hipocalcina/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , AVC Isquêmico/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Modelos Animais de Doenças
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