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1.
J Lipid Res ; 65(6): 100558, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729350

RESUMO

Metabolic dysfunction-associated steatotic liver disease is the most common form of liver disease and poses significant health risks to patients who progress to metabolic dysfunction-associated steatohepatitis. Fatty acid overload alters endoplasmic reticulum (ER) calcium stores and induces mitochondrial oxidative stress in hepatocytes, leading to hepatocellular inflammation and apoptosis. Obese mice have impaired liver sarco/ER Ca2+-ATPase (SERCA) function, which normally maintains intracellular calcium homeostasis by transporting Ca2+ ions from the cytoplasm to the ER. We hypothesized that restoration of SERCA activity would improve diet-induced steatohepatitis in mice by limiting ER stress and mitochondrial dysfunction. WT and melanocortin-4 receptor KO (Mc4r-/-) mice were placed on either chow or Western diet (WD) for 8 weeks. Half of the WD-fed mice were administered CDN1163 to activate SERCA, which reduced liver fibrosis and inflammation. SERCA activation also restored glucose tolerance and insulin sensitivity, improved histological markers of metabolic dysfunction-associated steatohepatitis, increased expression of antioxidant enzymes, and decreased expression of oxidative stress and ER stress genes. CDN1163 decreased hepatic citric acid cycle flux and liver pyruvate cycling, enhanced expression of mitochondrial respiratory genes, and shifted hepatocellular [NADH]/[NAD+] and [NADPH]/[NADP+] ratios to a less oxidized state, which was associated with elevated PUFA content of liver lipids. In sum, the data demonstrate that pharmacological SERCA activation limits metabolic dysfunction-associated steatotic liver disease progression and prevents metabolic dysfunction induced by WD feeding in mice.


Assuntos
Fígado , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Animais , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Camundongos , Fígado/metabolismo , Fígado/patologia , Masculino , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Estresse do Retículo Endoplasmático , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Dieta Ocidental/efeitos adversos , Camundongos Knockout
2.
J Transl Med ; 22(1): 622, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965536

RESUMO

BACKGROUND: Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. METHODS: We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton's tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS. RESULTS: Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. CONCLUSIONS: Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.


Assuntos
Tirosina Quinase da Agamaglobulinemia , Linfoma de Célula do Manto , Inibidores de Proteínas Quinases , Humanos , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Animais , Tirosina Quinase da Agamaglobulinemia/metabolismo , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Biomarcadores/metabolismo
3.
Appl Environ Microbiol ; 90(3): e0184623, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38319087

RESUMO

Horticultural diseases caused by bacterial pathogens provide an obstacle to crop production globally. Management of the infection of kiwifruit by the Gram-negative phytopathogen Pseudomonas syringae pv. actinidiae (Psa) currently includes copper and antibiotics. However, the emergence of bacterial resistance and a changing regulatory landscape are providing the impetus to develop environmentally sustainable antimicrobials. One potential strategy is the use of bacteriophage endolysins, which degrade peptidoglycan during normal phage replication, causing cell lysis and the release of new viral progeny. Exogenous use of endolysins as antimicrobials is impaired by the outer membrane of Gram-negative bacteria that provides an impermeable barrier and prevents endolysins from accessing their target peptidoglycan. Here, we describe the synergy between citric acid and a phage endolysin, which results in a reduction of viable Psa below detection. We show that citric acid drives the destabilization of the outer membrane via acidification and sequestration of divalent cations from the lipopolysaccharide, which is followed by the degradation of the peptidoglycan by the endolysin. Scanning electron microscopy revealed clear morphological differences, indicating cell lysis following the endolysin-citric acid treatment. These results show the potential for citric acid-endolysin combinations as a possible antimicrobial approach in agricultural applications. IMPORTANCE: The phytopathogen Pseudomonas syringae pv. actinidiae (Psa) causes major impacts to kiwifruit horticulture, and the current control strategies are heavily reliant on copper and antibiotics. The environmental impact and increasing resistance to these agrichemicals are driving interest in alternative antimicrobials including bacteriophage-derived therapies. In this study, we characterize the endolysin from the Otagovirus Psa374 which infects Psa. When combined with citric acid, this endolysin displays an impressive antibacterial synergy to reduce viable Psa below the limit of detection. The use of citric acid as a synergistic agent with endolysins has not been extensively studied and has never been evaluated against a plant pathogen. We determined that the synergy involved a combination of the chelation activity of citric acid, acidic pH, and the specific activity of the ΦPsa374 endolysin. Our study highlights an exciting opportunity for alternative antimicrobials in agriculture.


Assuntos
Actinidia , Bacteriófagos , Endopeptidases , Pseudomonas syringae , Cobre , Peptidoglicano , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Antibacterianos/farmacologia , Actinidia/microbiologia
4.
New Phytol ; 242(3): 1218-1237, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38481030

RESUMO

Nitrogen is an essential nutrient for plant growth and serves as a signaling molecule to regulate gene expression inducing physiological, growth and developmental responses. An excess or deficiency of nitrogen may have adverse effects on plants. Studying nitrogen uptake will help us understand the molecular mechanisms of utilization for targeted molecular breeding. Here, we identified and functionally validated an NAC (NAM-ATAF1/2-CUC2) transcription factor based on the transcriptomes of two apple rootstocks with different nitrogen uptake efficiency. NAC1, a target gene of miR164, directly regulates the expression of the high-affinity nitrate transporter (MhNRT2.4) and citric acid transporter (MhMATE), affecting root nitrogen uptake. To examine the role of MhNAC1 in nitrogen uptake, we produced transgenic lines that overexpressed or silenced MhNAC1. Silencing MhNAC1 promoted nitrogen uptake and citric acid secretion in roots, and enhanced plant tolerance to low nitrogen conditions, while overexpression of MhNAC1 or silencing miR164 had the opposite effect. This study not only revealed the role of the miR164-MhNAC1 module in nitrogen uptake in apple rootstocks but also confirmed that citric acid secretion in roots affected nitrogen uptake, which provides a research basis for efficient nitrogen utilization and molecular breeding in apple.


Assuntos
Malus , Malus/genética , Malus/metabolismo , Nitrogênio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transporte Biológico , Ácido Cítrico/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Anal Biochem ; 691: 115553, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38697592

RESUMO

We describe a microwave-assisted, methanol and acetic acid-free, inexpensive method for rapid staining of SDS-PAGE proteins. Only citric acid, benzoic acid, and Coomassie brilliant blue G-250 (CBG) were used. Microwave irradiation reduced the detection duration, and proteins in a clear background were visualized within 30 min of destaining, after 2 min of fixing and 12 min of staining. By using this protocol, comparable band intensities were obtained to the conventional methanol/acetic acid method.


Assuntos
Ácido Acético , Eletroforese em Gel de Poliacrilamida , Metanol , Micro-Ondas , Proteínas , Eletroforese em Gel de Poliacrilamida/métodos , Metanol/química , Proteínas/análise , Ácido Acético/química , Coloração e Rotulagem/métodos , Corantes de Rosanilina/química
6.
Pharmacol Res ; 200: 107068, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38232908

RESUMO

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.


Assuntos
Antígenos CD , Leucopenia , Humanos , Camundongos , Animais , ADP-Ribosil Ciclase/metabolismo , ADP-Ribosil Ciclase 1 , Antígenos CD/genética , Antígenos de Diferenciação/genética , Glicoproteínas de Membrana , Peixe-Zebra/metabolismo , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico
7.
Periodontol 2000 ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978341

RESUMO

Regenerative periodontal therapy aims to form new cementum, periodontal ligament, and alveolar bone, all sealed by gingival tissue. The root surface acts as the wound margin during this regeneration process. Root surface biomodification (root conditioning/root decontamination), therefore, seems instrumental in promoting surface decontamination and enhancing tissue attachment by removing the smear layer, exposing collagen fibrils, and facilitating blood clot formation and stabilization. This review attempted to provide an all-encompassing, evidence-based assessment of the role of root surface biomodification in regenerative periodontal therapy, particularly in intrabony defects, furcation defects, and root coverage procedures. The reviewed evidence suggested that root conditioning agents, whether used independently or in conjunction with bone graft materials, biological agents, membranes, or connective tissue grafts, do not offer any clinical advantage regarding clinical attachment gain. Thus, integrating chemical methods with the mechanical root instrumentation process does not necessarily contribute to superior clinical outcomes.

8.
J Appl Microbiol ; 135(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449343

RESUMO

AIMS: This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis. METHODS AND RESULTS: The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20 g l-1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80 g l-1. CONCLUSIONS: I. terricola could successfully adjust its membrane structure and function below 60 g l-1 of citric acid. However, for citric acid concentrations above 80 g l-1, its structure and function were dramatically changed, which might result in reduced functionality.


Assuntos
Estruturas da Membrana Celular , Ácido Cítrico , Pichia , Ácido Cítrico/farmacologia , Ácidos Graxos/farmacologia , Membrana Celular , Fluidez de Membrana
9.
Environ Res ; 245: 117981, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142729

RESUMO

The degradation of organic pollution by sulfur-modified nano zero-valent iron(S-nZVI) combined with advanced oxidation systems has been extensively studied. However, the low utilization of nZVI and low reactive oxygen species (ROS) yield in the system have limited its wide application. Herein, a natural organic acid commonly found in citrus fruits, citric acid (CA), was combined with the conventional S-nZVI@Ps system to enhance the degradation of norfloxacin (NOR). The addition of CA increased the NOR removal by about 31% compared with the conventional S-nZVI@Ps system under the same experimental conditions. Among them, the enhanced effect of CA is mainly reflected in its ability to promote the release of Fe2+ and accelerate the cycling of Fe2+ and Fe3+ to further improve the utilization of nZVI and the generation of ROS; it also promotes the dissolution of the active substance (FeS) on the surface of S-nZVI to further improve the degradation rate of NOR. More importantly, the chelate of CA and Fe2+ (CA-Fe2+) had higher reactivity than alone Fe2+. Free radical quenching and electron spin resonance (ESR) experiments indicated that the main ROS for the degradation of NOR in the CA/S-nZVI@Ps system were SO4•- and OH•. CA-bound sulfur-modifying effects on NOR degradation was systematically investigated, and the degradation mechanism of NOR in CA/S-nZVI@Ps system was explored by various techniques. Additionally, the effect of common anions in water matrix on the degradation of NOR in CA/S-nZVI@Ps system and its degradation of various pollutants were also studied. This study provides a new perspective to enhance the degradation of pollutants by S-nZVI combined with advanced oxidation system, which can help to solve the application boundary problem of S-nZVI.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Norfloxacino , Ácido Cítrico , Espécies Reativas de Oxigênio , Poluentes Químicos da Água/análise , Citratos , Enxofre
10.
Environ Res ; 249: 118421, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38325790

RESUMO

Root exudate is a major source of soil organic matter and can significantly affect arsenic (As) migration and transformation in paddy soils. Citric acid is the main component of rice root exudate, however, the impacts and rules of citric acid on As bioavailability and rhizobacteria in different soils remains unclear. This study investigated the effects of citric acid on As transformation and microbial community in ten different paddy soils by flooded soil culture experiments. The results showed that citric acid addition increased total As and arsenate (As(V)) in the soil porewater by up to 41-fold and 65-fold, respectively, after 2-h incubation. As(V) was the main As species in soil porewater within 10 days with the addition of citric acid. Non-specifically sorbed As of soils, total Fe and total As were the main environmental factors affecting the soil microbial communities. High-throughput sequencing analysis demonstrated that citric acid addition significantly altered the soil microbial community structure, shifting the Proteobacteria-related reducing bacteria to Firmicutes-related reducing bacteria in different paddy soils. The relative abundance of Firmicutes was promoted by 174-196%. Clostridium-related bacteria belonging to Firmicutes became the dominant genera, which is believed to regulate As release through the reductive dissolution of iron oxides or the direct reduction of As(V) to arsenite (As(III)). However, citric acid addition significantly decreased the relative abundance of Geobacter and Anaeromyxobacter, which are also typical active As(V)- and ferric-reducing bacteria. Real-time quantitative polymerase chain reaction (qPCR) also revealed that the addition of citric acid significantly decreased the relative abundances of Geobacter in the different soils by 8-28 times while the relative abundances of Clostridium increased by 2-5 times. These results provide significant insight on As transformation in different types of rice rhizospheric soils and guidance for the application of rice varieties with low citric acid exuding to restrict As accumulation.


Assuntos
Arsênio , Ácido Cítrico , Oryza , Microbiologia do Solo , Poluentes do Solo , Arsênio/análise , Poluentes do Solo/análise , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Microbiota/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/classificação , Solo/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-39089868

RESUMO

Methanol reportedly stimulates citric acid (CA) production by Aspergillus niger and A. tubingensis; however, the underlying mechanisms remain unclear. Here, we elucidated the molecular functions of the citrate exporter gene cexA in relation to CA production by Aspergillus tubingensis WU-2223L. Methanol addition to the medium containing glucose as a carbon source markedly increased CA production by strain WU-2223L by 3.38-fold, resulting in a maximum yield of 65.5 g/L, with enhanced cexA expression. Conversely, the cexA-complementing strain with the constitutive expression promoter Ptef1 (strain LhC-1) produced 68.3 or 66.7 g/L of CA when cultivated without or with methanol, respectively. Additionally, strain LhC-2 harboring two copies of the cexA expression cassette produced 80.7 g/L of CA without methanol addition. Overall, we showed that cexA is a target gene for methanol in CA hyperproduction by A. tubingensis WU-2223L. Based on these findings, methanol-independent CA-hyperproducing strains, LhC-1 and LhC-2, were successfully generated.

12.
Anim Biotechnol ; 35(1): 2379897, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39102232

RESUMO

The objectives of this study were to estimate genetic parameters for citric acid content (CA) and lactic acid content (LA) in sheep milk and to identify the associated candidate genes in a New Zealand dairy sheep flock. Records from 165 ewes were used. Heritability estimates based on pedigree records for CA and LA were 0.65 and 0.33, respectively. The genetic and phenotypic correlations between CA and LA were strong-moderate and negative. Estimates of genomic heritability for CA and LA were also high (0.85, 0.51) and the genomic correlation between CA and LA was strongly negative (-0.96 ± 0.11). No significant associations were found at the Bonferroni level. However, one intragenic SNP in C1QTNF1 (chromosome 11) was associated with CA, at the chromosomal significance threshold. Another SNP associated with CA was intergenic (chromosome 15). For LA, the most notable SNP was intragenic in CYTH1 (chromosome 11), the other two SNPs were intragenic in MGAT5B and TIMP2 (chromosome 11), and four SNPs were intergenic (chromosomes 1 and 24). The functions of candidate genes indicate that CA and LA could potentially be used as biomarkers for energy balance and clinical mastitis. Further research is recommended to validate the present results.


Assuntos
Ácido Cítrico , Estudo de Associação Genômica Ampla , Ácido Láctico , Leite , Polimorfismo de Nucleotídeo Único , Animais , Leite/química , Feminino , Ovinos/genética , Nova Zelândia , Polimorfismo de Nucleotídeo Único/genética , Ácido Cítrico/análise , Ácido Láctico/metabolismo
13.
Int Endod J ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888363

RESUMO

BACKGROUND: The dental pulp's environment is essential for the regulation of mesenchymal stem cells' homeostasis and thus, it is of great importance to evaluate the materials used in regenerative procedures. AIM: To assess in vitro (i) the effect of chitosan nanoparticles, 0.2% chitosan irrigation solution, Dual Rinse®, 17% EDTA, 10% citric acid and 2.5% NaOCl on DSCS viability; (ii) the effect of different concentrations of TGF-ß1 on DCSC proliferation; and (iii) whether treatment with TGF-ß1 following exposure to the different irrigation solutions could compensate for their negative effects. METHODOLOGY: (i) DSCS were treated with three dilutions (1:10, 1:100 and 1:1000) of the six irrigation solutions prepared in DMEM for 10 and 60 min to assess the effect on viability. (ii) The effect of different concentrations (0, 1, 5 and 10 ng/mL) of TGF-ß1 on DCSC proliferation was assessed at 1, 3 and 7 days. (iii) The proliferative effect of TGF-ß1 following 10-min exposure to 1:10 dilution of each irrigation solution was also tested. We used MTT assay to assess viability and proliferation. We performed statistical analysis using Prism software. RESULTS: (i) The different endodontic irrigation solutions tested showed a significant effect on cell viability (p ≤ .0001). Significant interactions between the endodontic irrigation solutions and their dilutions were also found for all parameters (p ≤ .0001). Chitosan nanoparticles and 0.2% chitosan irrigation solution were the least cytotoxic to DSCS whilst 2.5% NaOCl was the most cytotoxic followed by 17% EDTA. (ii) TGF-ß1 at concentrations of 1 and 5 ng/mL resulted in significantly higher proliferation compared to the control group. (iii) Exposure to 17% EDTA or 2.5% NaOCl for 10 min was sufficient to make DSCS cells refractory to the proliferative effects of TGF-ß1. DSCS groups treated with TGF-ß1 following exposure to chitosan nanoparticles, 0.2% chitosan irrigation solution, Dual Rinse® and 10% CA demonstrated significantly higher proliferation compared to non-TGF-ß1-treated groups (p ≤ .0001, p ≤ .0001, p ≤ .0001 and p = .01 respectively). CONCLUSIONS: The current study offers data that can be implemented to improve the outcome of regenerative endodontic procedures by using less toxic irrigation solutions and adding TGF-ß1 to the treatment protocol.

14.
J Labelled Comp Radiopharm ; 67(3): 86-90, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171549

RESUMO

[1'-13 C]Citric acid (1) was efficiently prepared from dimethyl 1,3-acetonedicarboxylate in two steps as a probe for a breath test. The synthetic method was selected because of the yield and reproducibility. Compound 1 was orally administrated to rats, and the time course of the increase of 13 CO2 /12 CO2 ratios (Δ13 CO2 ) in their breath was successfully followed, indicating the metabolism of 1. Thus, the 13 C-breath test using 1 is a promising method to evaluate tricarboxylic acid (TCA) cycle flux.


Assuntos
Ciclo do Ácido Cítrico , Ácido Cítrico , Ratos , Animais , Dióxido de Carbono , Reprodutibilidade dos Testes , Testes Respiratórios
15.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38279237

RESUMO

Amidst increasing concern about antibiotic resistance resulting from the overuse of antibiotics, there is a growing interest in exploring alternative agents. One such agent is citric acid, an organic compound commonly used for various applications. Our research findings indicate that the inclusion of citric acid can have several beneficial effects on the tight junctions found in the mouse intestine. Firstly, the study suggests that citric acid may contribute to weight gain by stimulating the growth of intestinal epithelial cells (IE-6). Citric acid enhances the small intestinal villus-crypt ratio in mice, thereby promoting intestinal structural morphology. Additionally, citric acid has been found to increase the population of beneficial intestinal microorganisms, including Bifidobacterium and Lactobacillus. It also promotes the expression of important protein genes such as occludin, ZO-1, and claudin-1, which play crucial roles in maintaining the integrity of the tight junction barrier in the intestines. Furthermore, in infected IEC-6 cells with H9N2 avian influenza virus, citric acid augmented the expression of genes closely associated with the influenza virus infection. Moreover, it reduces the inflammatory response caused by the viral infection and thwarted influenza virus replication. These findings suggest that citric acid fortifies the intestinal tight junction barrier, inhibits the replication of influenza viruses targeting the intestinal tract, and boosts intestinal immune function.


Assuntos
Vírus da Influenza A Subtipo H9N2 , Influenza Humana , Animais , Camundongos , Humanos , Ácido Cítrico/farmacologia , Ácido Cítrico/metabolismo , Influenza Humana/metabolismo , Intestinos/microbiologia , Mucosa Intestinal/metabolismo , Junções Íntimas/metabolismo , Imunidade
16.
Molecules ; 29(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731508

RESUMO

This study delves into the physicochemical properties of inorganic hydroxyapatite (HAp) and hybrid hydroxyapatite-chitosan (HAp-CTS) granules, also gold-enriched, which can be used as aggregates in biomicroconcrete-type materials. The impact of granules' surface modifications with citric acid (CA) or polyethylene glycol (PEG) was assessed. Citric acid modification induced increased specific surface area and porosity in inorganic granules, contrasting with reduced parameters in hybrid granules. PEG modification resulted in a slight increase in specific surface area for inorganic granules and a substantial rise for hybrid granules with gold nanoparticles. Varied effects on open porosity were observed based on granule type. Microstructural analysis revealed increased roughness for inorganic granules post CA modification, while hybrid granules exhibited smoother surfaces. Novel biomicroconcretes, based on α-tricalcium phosphate (α-TCP) calcium phosphate cement and developed granules as aggregates within, were evaluated for compressive strength. Compressive strength assessments showcased significant enhancement with PEG modification, emphasizing its positive impact. Citric acid modification demonstrated variable effects, depending on granule composition. The incorporation of gold nanoparticles further enriched the multifaceted approach to enhancing calcium phosphate-based biomaterials for potential biomedical applications. This study demonstrates the pivotal role of surface modifications in tailoring the physicochemical properties of granules, paving the way for advanced biomicroconcretes with improved compressive strength for diverse biomedical applications.

17.
Molecules ; 29(7)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38611930

RESUMO

The ability of ß-CD to form inclusion complexes with ibuprofen (IBU) and at the same time to make a two-phase system with citric acid was explored in the present study for achieving improved solubility and dissolution rate of IBU. Mechanical milling as well as mechanical milling combined with thermal annealing of the powder mixtures were applied as synthetic methods. Solubility and dissolution kinetics of the complexes were studied in compliance with European Pharmacopoeia (ICH Q4B). ß-CD and citric acid (CA) molecules were shown to interact by both ball milling (BM), thermal annealing, as well as BM with subsequent annealing. Complexes were also formed by milling the three compounds (ß-CD, CA and IBU) simultaneously, as well as by a consecutive first including IBU into ß-CD and then binding the formed ß-CD/IBU inclusion complex with CA. As a result, ternary ß-CD/IBU/CA complex formed by initial incorporation of ibuprofen into ß-CD, followed by successive formation of a two-phase mixture with CA, exhibited notably improved dissolution kinetics compared to the pure ibuprofen and slightly better compared to the binary ß-CD/IBU system. Although the addition of CA to ß-CD/IBU does not significantly increase the solubility rate of IBU, it must be considered that the amount of ß-CD is significantly less in the ternary complex compared to the binary ß-CD/IBU.


Assuntos
Ibuprofeno , beta-Ciclodextrinas , Solubilidade , Ácido Cítrico , Cinética
18.
Molecules ; 29(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38998911

RESUMO

In this study, a PtSn/Al2O3 catalyst with bimetallic uniform distribution in the sphere was synthesized. The PDH performance and characterization analyses, such as with FTIR, XPS, and NH3-TPD, were investigated. The effects of acid on the PDH performance were analyzed. Citric acid (CA) acted as a competing adsorbent in the preparation process of the PtSn/Al2O3 catalyst to synthesize the uniform catalyst. Water washing and alkali-treated samples were also studied. SEM line scanning revealed that increased the apparent concentration of Pt metal from 0.23 to 0.30 with citric acid. In contrast to the fresh PtSn/Al2O3 catalyst, the addition of citric acid increased the PDH selectivity from 74% to 93%. After alkali or water washing treatments, the catalyst's selectivity further increased to 96%. Strong acid sites promoted the breaking of C-C bonds during the PDH reaction, resulting in more methane and ethylene byproducts, and decreased catalyst selectivity for fresh PtSn/Al2O3. From the PDH reaction thermodynamic analysis, a relatively sub-atmospheric pressure environment with a lower propane pressure could be the reasonable choice.

19.
Environ Geochem Health ; 46(8): 275, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958819

RESUMO

Soil organic matter plays an important role in cadmium adsorption and immobilization. Since different organic matter components affect cadmium adsorption processes differently, selecting the right organic substrate and knowing how to apply it could improve cadmium remediation. This study compares the effects of two contrasting organic molecules; chitosan and citric acid, on cadmium adsorption and speciation in acidic Ultisol. The adsorption of chitosan to Ultisol significantly increased the soil positive charge while adsorption of citric acid increased the soil negative charge. At pH 5.0, the maximum amount of cadmium adsorbed in excess chitosan was 341% greater than that in excess citric acid. About 73-89% and 60-62% of adsorbed cadmium were bound to Fe/Mn oxides and organic matter/sulfide at pH 4.0 while this fraction was 77-100% and 57-58% for citric acid and chitosan at pH 5.0, respectively. This decrease in the complexing ability of chitosan was related to the destabilizing effect of high pH on chitosan's structure. Also, the sequence through which chitosan, citric acid, and cadmium were added into the adsorption system influenced the adsorption profile and this was different along a pH gradient. Specifically, adding chitosan and cadmium together increased adsorption compared to when chitosan was pre-adsorbed within pH 3.0-6.5. However, for citric acid, the addition sequence had no significant effect on cadmium adsorption between pH 3.0-4.0 compared to pH 6.5 and 7.5, with excess citric acid generally inhibiting adsorption. Given that the action of citric acid is short-lived in soil, chitosan could be a good soil amendment material for immobilizing cadmium.


Assuntos
Cádmio , Quitosana , Ácido Cítrico , Poluentes do Solo , Solo , Quitosana/química , Ácido Cítrico/química , Cádmio/química , Adsorção , Poluentes do Solo/química , Solo/química , Concentração de Íons de Hidrogênio , Recuperação e Remediação Ambiental/métodos
20.
Environ Geochem Health ; 46(8): 282, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963450

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants with carcinogenic, mutagenic and teratogenic effects. The white-rot fungi in the fungal group have significant degradation ability for high molecular weight organic pollutants. However, exogenous fungi are easily antagonized by indigenous microorganisms. Low molecular weight organic acids, a small molecular organic matter secreted by plants, can provide carbon sources for soil microorganisms. Combining organic acids with white rot fungi may improve the nutritional environment of fungi. In this study, immobilized Trametes versicolor was used to degrade benzo[a]pyrene in soil, and its effect on removing benzo[a]pyrene in soil mediated by different low molecular weight organic acids was investigated. The results showed that when the degradation was 35 days, the removal effect of the experimental group with citric acid was the best, reaching 43.7%. The degradation effect of Trametes versicolor on benzo[a]pyrene was further investigated in the liquid medium when citric acid was added, and the effects of citric acid on the biomass, extracellular protein concentration and laccase activity of Trametes versicolor were investigated by controlling different concentrations of citric acid. In general, citric acid can act as a carbon source for Trametes versicolor and promote its extracellular protein secretion and laccase activity, thereby accelerating the mineralization of benzo[a]pyrene by Trametes versicolor. Therefore, citric acid can be used as a biostimulant in the remediation of PAHs contaminated soil with Trametes versicolor.


Assuntos
Benzo(a)pireno , Biodegradação Ambiental , Ácido Cítrico , Poluentes do Solo , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Ácido Cítrico/metabolismo , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Lacase/metabolismo , Microbiologia do Solo , Polyporaceae/metabolismo , Trametes/metabolismo , Biomassa
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