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1.
Food Res Int ; 194: 114934, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39232545

RESUMO

Potassium citrate (KC) and potassium lactate (KL) are considered as salt replacers due to their saltiness, processing advantages, and health benefits. However, the obvious bitter taste associated with these compounds has limited their use in salt substitutes. Despite this challenge, little attention has been paid to improving their sensory properties. This study provided evidence that dietary polysaccharide carrageenan can effectively mask the bitterness of KC and KL by specifically binding K+ and forming double helix chains. A highly accurate prediction model was then established for the saltiness and bitterness of low-sodium salts using mixture design principles. Three low-sodium salt formulas containing different potassium salts (KC, KL, KCl), NaCl, and carrageenan were created based on the prediction model. These formulas exhibited favorable saltiness potencies (>0.85) without any noticeable odor, preserving the sensory characteristics of high-sodium food products like seasoning powder while significantly reducing their sodium content. This research provides a promising approach for the food industry to formulate alternative low-sodium products with substantially reduced sodium content, potentially contributing to decreased salt intake.


Assuntos
Paladar , Humanos , Cloreto de Sódio na Dieta , Citrato de Potássio/química , Carragenina/química , Masculino , Feminino , Polissacarídeos/química , Adulto , Compostos de Potássio/química , Lactatos/química , Dieta Hipossódica
2.
Int J Biol Macromol ; 279(Pt 1): 135133, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39208882

RESUMO

Chiral phenyllactic acid (PLA) is a new type of antiseptic agent and a valuable precursor for active ingredients in pharmaceuticals and agrochemicals. In this study, we designed a multi-enzyme cascade that combined stereocomplementary d- and l-lactate dehydrogenases with threonine aldolase, phenylserine dehydratase, and formate dehydrogenase for the one-pot conversion of achiral glycine and benzaldehyde to synthesize d-PLA and l-PLA. To overcome the imbalance of multi-enzymes in a single cell, two enzyme modules, overexpressing four enzymes, were assembled in Escherichia coli cells to construct whole-cell catalysis systems (WCCSs). Furthermore, by optimizing reaction conditions and components, recombinant E. coli (WCCS 26) was able to produce 100 mM d-PLA with >99 % ee using a fed-batch strategy, while E. coli (WCCS 60) produced 47.2 mM l-PLA with >99 % ee. This study presents a sustainable and efficient method for synthesizing chiral PLAs from food-grade achiral starting materials.


Assuntos
Escherichia coli , Lactatos , Escherichia coli/genética , Estereoisomerismo , Lactatos/química , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/química , L-Lactato Desidrogenase/genética , Formiato Desidrogenases/metabolismo , Formiato Desidrogenases/química , Formiato Desidrogenases/genética , Lactato Desidrogenases
3.
Chem Biol Interact ; 400: 111162, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39047806

RESUMO

Non-alcoholic fatty liver disease (NAFLD) affects approximately a quarter of the population and, to date, there is no approved drug therapy for this condition. Individuals with type 2 diabetes mellitus (T2DM) are at a significantly elevated risk of developing NAFLD, underscoring the urgency of identifying effective NAFLD treatments for T2DM patients. Salvianolic acid A (SAA) is a naturally occurring phenolic acid that is an important component of the water-soluble constituents isolated from the roots of Salvia miltiorrhiza Bunge. SAA has been demonstrated to possess anti-inflammatory and antioxidant stress properties. Nevertheless, its potential in ameliorating diabetes-associated NAFLD has not yet been fully elucidated. In this study, diabetic ApoE-/- mice were employed to establish a NAFLD model via a Western diet. Following this, they were treated with different doses of SAA (10 mg/kg, 20 mg/kg) via gavage. The study demonstrated a marked improvement in liver injury, lipid accumulation, inflammation, and the pro-fibrotic phenotype after the administration of SAA. Additionally, RNA-seq analysis indicated that the primary pathway by which SAA alleviates diabetes-induced NAFLD involves the cascade pathways of lipid metabolism. Furthermore, SAA was found to be effective in the inhibition of lipid accumulation, mitochondrial dysfunction and ferroptosis. A functional enrichment analysis of RNA-seq data revealed that SAA treatment modulates the AMPK pathway and IGFBP-1. Further experimental results demonstrated that SAA is capable of inhibiting lipid accumulation through the activation of the AMPK pathway and IGFBP-1.


Assuntos
Proteínas Quinases Ativadas por AMP , Ácidos Cafeicos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina , Lactatos , Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Camundongos , Lactatos/farmacologia , Lactatos/uso terapêutico , Lactatos/química , Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/química , Ácidos Cafeicos/uso terapêutico , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Masculino , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Knockout
4.
Int J Toxicol ; 43(4_suppl): 108-129, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39039928

RESUMO

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 10 alkanoyl lactyl lactate salts. These ingredients have the surfactant function in cosmetics in common. The Panel reviewed data relevant to the safety of these ingredients, and concluded that these 10 ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be nonirritating and nonsensitizing, which may be based on a quantitative risk assessment (QRA) or other accepted methodologies.


Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos , Cosméticos/toxicidade , Cosméticos/química , Humanos , Animais , Medição de Risco , Lactatos/toxicidade , Lactatos/química , Testes de Toxicidade , Tensoativos/toxicidade , Tensoativos/química , Tensoativos/farmacocinética
6.
Sci Rep ; 14(1): 12427, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816543

RESUMO

Intracerebral hemorrhage (ICH) is a common cerebral vascular disease with high incidence, disability, and mortality. Ferroptosis is a regulated type of iron-dependent, non-apoptotic programmed cell death. There is increasing evidence that ferroptosis may lead to neuronal damage mediated by hemorrhagic stroke mediated neuronal damage. Salvianolic acid A (SAA) is a natural bioactive polyphenol compound extracted from salvia miltiorrhiza, which has anti-inflammatory, antioxidant, and antifibrosis activities. SAA is reported to be an iron chelator that inhibits lipid peroxidation and provides neuroprotective effects. However, whether SAA improves neuronal ferroptosis mediated by hemorrhagic stroke remains unclear. The study aims to evaluate the therapeutic effect of SAA on Ferroptosis mediated by Intracerebral hemorrhage and explore its potential mechanisms. We constructed in vivo and in vitro models of intracerebral hemorrhage in rats. Multiple methods were used to analyze the inhibitory effect of SAA on ferroptosis in both in vivo and in vitro models of intracerebral hemorrhage in rats. Then, network pharmacology is used to identify potential targets and mechanisms for SAA treatment of ICH. The SAA target ICH network combines SAA and ICH targets with protein-protein interactions (PPIs). Find the specific mechanism of SAA acting on ferroptosis through molecular docking and functional enrichment analysis. In rats, SAA (10 mg/kg in vivo and 50 µM in vitro, p < 0.05) alleviated dyskinesia and brain injury in the ICH model by inhibiting ferroptosis (p < 0.05). The molecular docking results and functional enrichment analyses suggested that AKT (V-akt murine thymoma viral oncogene homolog) could mediate the effect of SAA. NRF2 (Nuclear factor erythroid 2-related factor 2) was a potential target of SAA. Our further experiments showed that salvianolic acid A enhanced the Akt /GSK-3ß/Nrf2 signaling pathway activation in vivo and in vitro. At the same time, SAA significantly expanded the expression of GPX4, XCT proteins, and the nuclear expression of Nrf2, while the AKT inhibitor SH-6 and the Nrf2 inhibitor ML385 could reduce them to some extent. Therefore, SAA effectively ameliorated ICH-mediated neuronal ferroptosis. Meanwhile, one of the critical mechanisms of SAA inhibiting ferroptosis was activating the Akt/GSK-3ß/Nrf2 signaling pathway.


Assuntos
Ácidos Cafeicos , Hemorragia Cerebral , Ferroptose , Lactatos , Fármacos Neuroprotetores , Animais , Ferroptose/efeitos dos fármacos , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/química , Ratos , Lactatos/farmacologia , Lactatos/química , Lactatos/uso terapêutico , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Fator 2 Relacionado a NF-E2/metabolismo , Simulação de Acoplamento Molecular , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo
7.
Food Chem ; 453: 139601, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38754350

RESUMO

Phenyllactic acid (PLA) as a natural phenolic acid exhibits antibacterial activity against non-spore-forming bacteria, while the inhibitory effect against bacterial spore remained unknown. Herein, this study investigated the inactivation effect of PLA against Bacillus cereus spores. The results revealed that the minimum inhibitory concentration of PLA was 1.25 mg/mL. PLA inhibited the outgrowth of germinated spores into vegetative cells rather than germination of spores. PLA disrupted the spore coat, and damaged the permeability and integrity of inner membrane. Moreover, PLA disturbed the establishment of membrane potential due to the inhibition of oxidative metabolism. SEM observations further visualized the morphological changes and structural disruption caused by PLA. Besides, PLA caused the degradation of DNA of germinated spores. Finally, PLA was applied in milk beverage, and showed promising inhibitory effect against B. cereus spores. This finding could provide scientific basis for the application of PLA against spore-forming bacteria in food industry.


Assuntos
Antibacterianos , Bacillus cereus , Leite , Esporos Bacterianos , Bacillus cereus/crescimento & desenvolvimento , Bacillus cereus/efeitos dos fármacos , Bacillus cereus/metabolismo , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/crescimento & desenvolvimento , Esporos Bacterianos/metabolismo , Leite/química , Leite/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Bebidas/análise , Bebidas/microbiologia , Testes de Sensibilidade Microbiana , Lactatos/farmacologia , Lactatos/química , Lactatos/metabolismo
8.
Int J Biol Macromol ; 271(Pt 1): 132618, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38795880

RESUMO

High-temperature blanching (HTB) is the primary process that causes texture softening in frozen yellow peaches. The implementation of low-temperature blanching reduced pectin methyl esterification, increased pectin cross-linking, and mitigated pectin depolymerization during the subsequent HTB, leading to the superior texture of frozen yellow peaches with enhanced water holding capacity, higher fracture stress, and initial modulus. However, adding 2 % calcium lactate (w/v) during low-temperature blanching did not further improve the texture of frozen yellow peaches. Instead, it softened the texture by reducing Na2CO3-soluble pectin (NSP) and increasing water-soluble pectin (WSP) content. This study provided a theoretical basis for applying low-temperature blanching to improve the texture of frozen yellow peaches.


Assuntos
Congelamento , Pectinas , Pectinas/química , Solubilidade , Água/química , Temperatura Baixa , Lactatos/química , Compostos de Cálcio/química , Prunus avium/química , Carbonatos/química
9.
Plant Foods Hum Nutr ; 79(2): 526-530, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530542

RESUMO

The antiglycation mechanisms of three structurally different salvianolic acids (Sals) including salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and salvianolic acid C (Sal-C) were investigated using the bovine serum albumin (BSA)-fructose model. The results showed that the three compounds could inhibit the formation of glycation products, maintain protein structural stability, mitigate the development of amyloid fibrils and scavenge radicals. Notably, Sal-A possessed the highest anti-glycated activity compared with Sal-B and Sal-C. This may be related to the fact that Sal-A contained the most molecules of caffeic acid (Sal-A, Sal-B, and Sal-C possessing two, one, and zero caffeic acid units, respectively), and caffeic acid played a leading role in the antiglycation properties relative to Danshensu. Moreover, these compounds quenched the intrinsic fluorescence intensity of BSA in a static mode, with the binding constants in the order of Sal-A > Sal-B > Sal-C. Obviously, Sal-A possessed the strongest binding affinity among these compounds, which may be one of the reasons why it exhibited the optimal antiglycation capability. Furthermore, molecular docking demonstrated that the three Sals exerted protective effects on BSA by preventing glycation modification of lysine and arginine residues. These findings would provide valuable insights into the potential application of Sals for alleviating non-enzymatic glycation of protein.


Assuntos
Benzofuranos , Ácidos Cafeicos , Lactatos , Polifenóis , Soroalbumina Bovina , Soroalbumina Bovina/química , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/química , Glicosilação/efeitos dos fármacos , Polifenóis/farmacologia , Polifenóis/química , Benzofuranos/farmacologia , Benzofuranos/química , Lactatos/farmacologia , Lactatos/química , Alcenos/farmacologia , Alcenos/química , Animais , Produtos Finais de Glicação Avançada/química , Produtos Finais de Glicação Avançada/metabolismo , Bovinos , Simulação de Acoplamento Molecular , Depsídeos
10.
Neurotherapeutics ; 21(3): e00342, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38493057

RESUMO

Novel therapeutics for the treatment of ischemic stroke remains to be the unmet clinical needs. Previous studies have indicated that salvianolic acid A (SAA) is a promising candidate for the treatment of the brain diseases. However, SAA has poor absolute bioavailability and does not efficiently cross the intact blood-brain barrier (BBB), which limit its efficacy. To this end we developed a brain-targeted liposomes for transporting SAA via the BBB by incorporating the liposomes to a transport receptor, insulin-like growth factor-1 receptor (IGF1R). The liposomes were prepared by ammonium sulfate gradients loading method. The prepared SAA-loaded liposomes (Lipo/SAA) were modified with IGF1R monoclonal antibody to generate IGF1R antibody-conjugated Lipo/SAA (IGF1R-targeted Lipo/SAA). The penetration of IGF1R-targeted Lipo/SAA into the brain was confirmed by labeling with Texas Red, and their efficacy were evaluate using middle cerebral artery occlusion (MCAO) model. The results showed that IGF1R-targeted Lipo/SAA are capable of transporting SAA across the BBB into the brain, accumulation in brain tissue, and sustained releasing SAA for several hours. Administration o IGF1R-targeted Lipo/SAA notably reduced infarct size and neuronal damage, improved neurological function and inhibited cerebral inflammation, which had much higher efficiency than no-targeted SAA.


Assuntos
AVC Isquêmico , Lipossomos , Animais , AVC Isquêmico/tratamento farmacológico , Masculino , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Receptor IGF Tipo 1/metabolismo , Camundongos , Lactatos/administração & dosagem , Lactatos/química , Infarto da Artéria Cerebral Média/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Ratos Sprague-Dawley , Ratos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos
11.
Channels (Austin) ; 17(1): 2273008, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37934721

RESUMO

Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these transporters play in oncogenesis, our objective was to look into the association of MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3) with Epithelial ovarian cancer (EOC) pathophysiology by exploiting various publicly available databases and web resources. Few of the in silico findings were confirmed via in vitro experiments in EOC cell lines, SKOV3 and OAW-42. MCT1 and MCT4 were found to be upregulated at the mRNA level in OC tissues compared to normal. However, only higher level of MCT4 mRNA was found to be associated with poor patient survival. MCT4 was positively correlated with gene families responsible for invasion, migration, and immune modification, proving it to be one of the most important MCTs for therapeutic intervention. We compared the effects of MCT1/2 blocker SR13800 and a broad-spectrum MCT blocker α-Cyano Hydroxy Cinnamic Acid (α-CHCA) and discovered that α-CHCA has a greater effect on diminishing the invasive behavior of the cancer cells than MCT1/2 blocker SR13800. From our study, MCT4 has emerged as a prospective marker for predicting poor patient outcomes and a potential therapeutic target.


Assuntos
Proteínas de Membrana Transportadoras , Neoplasias Ovarianas , Feminino , Humanos , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Estudos Prospectivos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Piruvatos/química , Piruvatos/metabolismo , Lactatos/química , Lactatos/metabolismo
12.
Acta Orthop Traumatol Turc ; 56(4): 289-295, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35968622

RESUMO

OBJECTIVE: This study aimed to analyze the frequency of postoperative kidney injury, the related factors, and its effect on outcomes in major orthopedic surgery cases treated in the postanesthesia intensive care unit (PACU). METHODS: Major orthopedic surgery cases treated in the PACU were included in this study retrospectively. Demographic, operation, and anesthesia characteristics, CCI, ASA risk classes, preoperative biochemistry, and hemogram results of the patients were recorded. Postoperative serum creatinine level, urine output, renal replacement therapy requirement, and hemoglobin levels were recorded. The kidney damage of the patients was evaluated with RIFLE and AKIN criteria. Postoperative complications were recorded. RESULTS: The frequency of kidney injury in the early postoperative period was 7.1%. When only arthroplasty cases were taken, the frequency was 11%. It was determined that there was a correlation between preoperative ASA, CCI, BMI, K levels, lactate levels, and postoperative kidney damage (P <0.05). It was determined that the frequency and duration of inotropic use, the frequency and duration of noninvasive mechanical ventilation, and the duration of hospitalization increased in patients with postoperative kidney damage, and the frequency of pneumonia, wound infection, atelectasis, sepsis, arrhythmia, atrial fibrillation and mortality increased in the postoperative period (P <0.05). CONCLUSION: There is a need for further studies on the relationship between ASA, CCI, BMI, K, and lactate values and postoperative kidney damage. Postoperative kidney injury is associated with prolonged hospitalization and increased morbidity and mortality. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.


Assuntos
Injúria Renal Aguda , Procedimentos Ortopédicos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Humanos , Lactatos/sangue , Lactatos/química , Procedimentos Ortopédicos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
13.
Mar Drugs ; 20(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35049900

RESUMO

Nowadays, the use of marine by-products as precursor materials has gained great interest in the extraction and production of chemical compounds with suitable properties and possible pharmaceutical applications. The present paper presents the development of a new immediate release tablet containing calcium lactate obtained from Black Sea mussel shells. Compared with other calcium salts, calcium lactate has good solubility and bioavailability. In the pharmaceutical preparations, calcium lactate was extensively utilized as a calcium source for preventing and treating calcium deficiencies. The physical and chemical characteristics of synthesized calcium lactate were evaluated using Fourier Transform Infrared Spectroscopy, X-ray diffraction analysis and thermal analysis. Further, the various pharmacotechnical properties of the calcium lactate obtained from mussel shells were determined in comparison with an industrial used direct compressible Calcium lactate DC (PURACAL®). The obtained results suggest that mussel shell by-products are suitable for the development of chemical compounds with potential applications in the pharmaceutical domain.


Assuntos
Bivalves , Compostos de Cálcio/química , Lactatos/química , Exoesqueleto , Animais , Organismos Aquáticos , Sistemas de Liberação de Medicamentos , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos , Difração de Raios X
14.
Food Funct ; 12(22): 11250-11261, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34708849

RESUMO

Microbial fermentation with lactic acid bacteria (LAB) is a natural food biopreservation method. Yellow mustard and milk whey are optimum substrates for LAB fermentation. The aim of the present study was to evaluate the bioaccessibility and bioavailability of bioactive compounds from yellow mustard flour and milk whey both with and without LAB fermentation. All extracts were subjected to a simulated digestion process. Total polyphenols, DL-3-phenyllactic acid (PLA), lactic acid, and the antioxidant activity were determined in the studied matrices before and after simulated digestion. Yellow mustard flour was significantly richer in total polyphenols, whereas significantly higher concentrations of PLA and lactic acid were observed in milk whey. Similar antioxidant activity was determined in both ingredients being in all cases strongly reduced after in vitro digestion. Higher bioaccessibility was found for polyphenols and PLA in milk whey. Transepithelial transport of total polyphenols was higher in yellow mustard flour compared to milk whey, reaching bioavailability values between 3-7% and 1-2%, respectively. PLA transepithelial transport was only significant in both fermented matrices with bioavailability around 4-6%. Transepithelial transport of lactic acid reached values of 31-34% (bioavailability ∼ 22%) and 15-78% (bioavailability ∼ 3%) in milk whey and yellow mustard flour, respectively. LAB fermentation showed beneficial effects on enriching extracts with PLA, lactic acid, and antioxidant activity, as well as increasing bioaccessibility of these acids in yellow mustard flour and total polyphenol bioavailability in milk whey. Results pointed to yellow mustard flour and milk whey as natural preservative ingredients used in the food industry, especially when fermented with LAB.


Assuntos
Antioxidantes , Lactobacillales/metabolismo , Leite/metabolismo , Mostardeira/química , Soro do Leite/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Células CACO-2 , Fermentação/fisiologia , Humanos , Lactatos/química , Lactatos/farmacocinética , Ácido Láctico/química , Ácido Láctico/farmacocinética
15.
Biomolecules ; 11(8)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34439752

RESUMO

Global agricultural intensification has prompted investigations into biostimulants to enhance plant nutrition and soil ecosystem processes. Metal lactates are an understudied class of organic micronutrient supplement that provide both a labile carbon source and mineral nutrition for plant and microbial growth. To gain a fundamental understanding of plant responses to metal lactates, we employed a series of sterile culture-vessel experiments to compare the uptake and toxicity of five metals (Zn, Mn, Cu, Ni, and Co) supplied in lactate and chloride salt form. Additionally, primary root growth in plate-grown Arabidopsis thaliana seedlings was used to determine optimal concentrations of each metal lactate. Our results suggest that uptake and utilization of metals in wheat (Triticum aestivum L.) when supplied in lactate form is comparable to that of metal chlorides. Metal lactates also have promotional growth effects on A. thaliana seedlings with optimal concentrations identified for Zn (0.5-1.0 µM), Mn (0.5-1.0 µM), Cu (0.5 µM), Ni (1.0 µM), and Co (0.5 µM) lactate. These findings present foundational evidence to support the use of metal lactates as potential crop biostimulants due to their ability to both supply nutrients and stimulate plant growth.


Assuntos
Arabidopsis/metabolismo , Cloretos/química , Lactatos/química , Metais/química , Ácidos/química , Agricultura/métodos , Quelantes , Ecossistema , Hidroponia , Ácido Láctico , Metais Pesados , Micronutrientes/química , Compostos Orgânicos , Plântula , Sementes/metabolismo , Solo , Poluentes do Solo/análise , Triticum , Zinco/química
16.
Chembiochem ; 22(22): 3158-3163, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34224197

RESUMO

Pharmacological inhibition of histone deacetylase 6 (HDAC6) is an effective therapeutic strategy for cancer and immunological diseases. Most of the previously reported HDAC6 inhibitors have a hydroxamate group as a zinc binding group (ZBG), which coordinates to the catalytic zinc ion of HDAC6. The hydroxamate group is liable to metabolically generate mutagenetic hydroxylamine; therefore, non-hydroxamate HDAC6 inhibitors would be advantageous. In this study, to identify novel non-hydroxamate HDAC6-selective inhibitors, screening of a chemical library and the subsequent structural optimization were performed, which led to the identification of HDAC6-selective inhibitors with 3,3,3-trifluorolactic amide (TFLAM) as a novel ZBG. The identified inhibitor showed potent and selective HDAC6-inhibitory activity in cells and induced regulatory T (Treg) cell differentiation.


Assuntos
Amidas/farmacologia , Desacetilase 6 de Histona/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Lactatos/farmacologia , Zinco/farmacologia , Amidas/química , Desacetilase 6 de Histona/metabolismo , Inibidores de Histona Desacetilases/química , Humanos , Lactatos/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Zinco/química
17.
Int J Biol Macromol ; 186: 849-863, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34245737

RESUMO

Chemotherapy drugs are still one of the first treatment options used in many cancers; however, problems such as cytotoxic side effects on normal cells after systemic administration and resistance to treatment have reduced the use of chemotherapeutics day by day. Targeted delivery of these drugs to the tumor site and sensitization of cancer cells to death induced by chemotherapy drugs are ways that can overcome the limitations of the use of these drugs. In this study, we designed and generated a novel nanocarrier composed of chitosan lactate nanoparticles (NPs) functionalized by HIV-1 derived TAT peptide (Transactivating transcriptional activator) and hyaluronate (HA) to deliver CD73 siRNA and doxorubicin to 4T1 and CT26 cancer cells, both in vivo and in vitro, as a novel combinatorial treatment strategy. The CD73 molecule plays a key role in many cancer cell behaviors such as proliferation, angiogenesis, metastasis, imunosuppression, and resistance to chemotherapy. Therefore, we decided to reduce the side effects of DOX by simultaneously transmitting CD73 siRNA and DOX by CL-TAT-HA NPs, increase the susceptibility of cancer cells to DOX-induced cell death, and stimulate anti-tumor immune responses, for the first time. These results indicated that simultaneous transfer of CD73 siRNA and DOX to cancer cells (4 T1 and CT26) increased cell death and inhibited the prolifration and spread of cancer cells. Also, the preferential aggregation of NPs in the tumor microenvironment reduced tumor growh, promoted the survival of tumor-bearing mice, and induced anti-tumor immune responses. These findings indicate that CL-TAT-HA NPs are a good candidate for targeted siRNA/drug delivery to cancer cells and the simultaneous transfer of CD73 siRNA and DOX to cancer cells using this nanocarrier can be used to treat cancer.


Assuntos
5'-Nucleotidase/genética , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/terapia , Quitosana/química , Neoplasias Colorretais/terapia , Doxorrubicina/farmacologia , Ácido Hialurônico/química , Lactatos/química , RNA Interferente Pequeno/genética , Terapêutica com RNAi , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química , 5'-Nucleotidase/metabolismo , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quitosana/análogos & derivados , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Doxorrubicina/química , Doxorrubicina/toxicidade , Composição de Medicamentos , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Nanotecnologia , Invasividade Neoplásica , Neovascularização Patológica , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo
18.
Mol Pharm ; 18(8): 2986-2996, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34196555

RESUMO

The aim of this study was to fabricate novel microparticles (MPs) for efficient and long-term delivery of amikacin (AMI). The emulsification method proposed for encapsulating AMI employed low-molecular-weight poly(lactic acid) (PLA) and poly(lactic acid-co-polyethylene glycol) (PLA-PEG), both supplemented with poly(vinyl alcohol) (PVA). The diameters of the particles obtained were determined as less than 30 µm. Based on an in-vitro release study, it was proven that the MPs (both PLA/PVA- and PLA-PEG/PVA-based) demonstrated long-term AMI release (2 months), the kinetics of which adhered to the Korsmeyer-Peppas model. The loading efficiencies of AMI in the study were determined at the followings levels: 36.5 ± 1.5 µg/mg for the PLA-based MPs and 106 ± 32 µg/mg for the PLA-PEG-based MPs. These values were relatively high and draw parallels with studies published on the encapsulation of aminoglycosides. The MPs provided antimicrobial action against the Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae bacterial strains. The materials were also comprehensively characterized by the following methods: differential scanning calorimetry; gel permeation chromatography; scanning electron microscopy; Fourier transform infrared spectroscopy-attenuated total reflectance; energy-dispersive X-ray fluorescence; and Brunauer-Emmett-Teller surface area analysis. The findings of this study contribute toward discerning new means for conducting targeted therapy with polar, broad spectrum antibiotics.


Assuntos
Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Lactatos/química , Poliésteres/química , Polietilenoglicóis/química , Amicacina/química , Antibacterianos/química , Cápsulas , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Peso Molecular , Tamanho da Partícula , Álcool de Polivinil/química , Pseudomonas aeruginosa/efeitos dos fármacos , Solubilidade , Staphylococcus aureus/efeitos dos fármacos
19.
J Bacteriol ; 203(19): e0036021, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34280003

RESUMO

Lactobacillus crispatus is a well-established probiotic with antimicrobial activity against pathogens across several niches of the human body generally attributed to the production of bacteriostatic molecules, including hydrogen peroxide and lactic acid. Here, we show that the cell-free supernatants of clinical isolates of L. crispatus harbor robust bactericidal activity. We further identify phenyl-lactic acid as a bactericidal compound with properties and a susceptibility range nearly identical to that of the cell-free supernatant. As such, we hypothesize that phenyl-lactic acid is a key active ingredient in L. crispatus supernatant. IMPORTANCE Although Lactobacillus crispatus is an established commensal microbe frequently used in probiotics, its protective role in the bladder microbiome has not been clarified. We report here that some urinary isolates of L. crispatus exhibit bactericidal activity, primarily due to its ability to excrete phenyl-lactic acid into its environment. Both cell-free supernatants of L. crispatus isolates and phenyl-lactic acid exhibit bactericidal activity against a wide range of pathogens, including several that are resistant to multiple antibiotics.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Lactatos/metabolismo , Lactatos/farmacologia , Lactobacillus crispatus/metabolismo , Anti-Infecciosos/metabolismo , Bactérias/efeitos dos fármacos , Candida/efeitos dos fármacos , Lactatos/química
20.
Mol Med ; 27(1): 80, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284715

RESUMO

PURPOSE: Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1ß is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1ß-induced inflammatory responses in OA. METHODS: IL-1ß was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining. RESULTS: DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1ß treated chondrocytes. In addition, DSS downregulated IL-1ß-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1ß-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo. CONCLUSIONS: Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.


Assuntos
Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Interleucina-1beta/metabolismo , Lactatos/farmacologia , NF-kappa B/metabolismo , Osteoartrite/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Matriz Extracelular/metabolismo , Mediadores da Inflamação/metabolismo , Lactatos/administração & dosagem , Lactatos/química , Camundongos , Osteoartrite/tratamento farmacológico , Osteoartrite/etiologia , Osteoartrite/patologia
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