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1.
AAPS PharmSciTech ; 25(5): 106, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724834

RESUMEN

The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9 nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5 mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2 µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo.


Asunto(s)
Antifúngicos , Biopelículas , Candida albicans , Quitosano , Pruebas de Sensibilidad Microbiana , Nanopartículas , Ácido Fítico , Quitosano/química , Biopelículas/efectos de los fármacos , Nanopartículas/química , Antifúngicos/farmacología , Antifúngicos/administración & dosificación , Animales , Candida albicans/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana/métodos , Ácido Fítico/farmacología , Ácido Fítico/administración & dosificación , Ácido Fítico/química , Femenino , Candidiasis/tratamiento farmacológico , Tamaño de la Partícula , Portadores de Fármacos/química , Reactivos de Enlaces Cruzados/química , Citocinas/metabolismo
2.
Biochem Pharmacol ; 222: 116118, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38467376

RESUMEN

Diabetes-related hyperglycemia inhibits bone marrow mesenchymal stem cell (BMSC) function, thereby disrupting osteoblast capacity and bone regeneration. Dietary supplementation with phytic acid (PA), a natural inositol phosphate, has shown promise in preventing osteoporosis and diabetes-related complications. Emerging evidence has suggested that circular (circ)RNAs implicate in the regulation of bone diseases, but their specific regulatory roles in BMSC osteogenesis in hyperglycemic environments remain elucidated. In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and triggered osteogenesis enhancement in BMSCs by targeting FOXO1 directly. Furthermore, circEIF4B inhibited the ubiquitin-mediated degradation of IGF2BP3, thereby stabilizing ITGA5 mRNA and promoting BMSC osteogenic differentiation. In vivo experiments, circEIF4B inhibition attenuated the effectiveness of PA treatment in diabetic rats with cranial defects. Collectively, our study identifies PA as a novel positive regulator of BMSC osteogenic differentiation through the circEIF4B/miR-186-5p/FOXO1 and circEIF4B/IGF2BP3/ITGA5 axes, which offers a new strategy for treating high glucose-mediatedBMSCosteogenic dysfunction and delayed bone regeneration in diabetes.


Asunto(s)
Diabetes Mellitus Experimental , Células Madre Mesenquimatosas , MicroARNs , Ratas , Animales , Osteogénesis , MicroARNs/metabolismo , Ácido Fítico/farmacología , Ácido Fítico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Glucosa/farmacología , Glucosa/metabolismo , Células de la Médula Ósea/metabolismo , Células Cultivadas
3.
ACS Chem Neurosci ; 15(6): 1157-1168, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38445956

RESUMEN

Phytic acid (PA) has been reported to possess anti-inflammatory and antioxidant properties that are critical for neuroprotection in neuronal disorders. This raises the question of whether PA can effectively protect sensory neurons against chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy is a dose-limiting side effect of chemotherapy treatment often characterized by severe and abnormal pain in hands and feet resulting from peripheral nerve degeneration. Currently, there are no effective treatments available that can prevent or cure peripheral neuropathies other than symptomatic management. Herein, we aim to demonstrate the neuroprotective effects of PA against the neurodegeneration induced by the chemotherapeutics cisplatin (CDDP) and oxaliplatin. Further aims of this study are to provide the proposed mechanism of PA-mediated neuroprotection. The neuronal protection and survivability against CDDP were characterized by axon length measurements and cell body counting of the dorsal root ganglia (DRG) neurons. A cellular phenotype study was conducted microscopically. Intracellular reactive oxygen species (ROS) was estimated by fluorogenic probe dichlorofluorescein. Likewise, mitochondrial membrane potential (MMP) was assessed by fluorescent MitoTracker Orange CMTMRos. Similarly, the mitochondria-localized superoxide anion radical in response to CDDP with and without PA was evaluated. The culture of primary DRG neurons with CDDP reduced axon length and overall neuronal survival. However, cotreatment with PA demonstrated that axons were completely protected and showed increased stability up to the 45-day test duration, which is comparable to samples treated with PA alone and control. Notably, PA treatment scavenged the mitochondria-specific superoxide radicals and overall intracellular ROS that were largely induced by CDDP and simultaneously restored MMP. These results are credited to the underlying neuroprotection of PA in a platinum-treated condition. The results also exhibited that PA had a synergistic anticancer effect with CDDP in ovarian cancer in vitro models. For the first time, PA's potency against CDDP-induced PN is demonstrated systematically. The overall findings of this study suggest the application of PA in CIPN prevention and therapeutic purposes.


Asunto(s)
Antineoplásicos , Enfermedades del Sistema Nervioso Periférico , Humanos , Antineoplásicos/toxicidad , Cisplatino/toxicidad , Ganglios Espinales , Potencial de la Membrana Mitocondrial , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/metabolismo , Ácido Fítico/farmacología , Ácido Fítico/metabolismo , Ácido Fítico/uso terapéutico , Platino (Metal)/farmacología , Platino (Metal)/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células Receptoras Sensoriales/metabolismo
4.
J Bone Miner Res ; 39(3): 197-201, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38477812

RESUMEN

Two months after her first pregnancy, a 35-yr-old exclusively breastfeeding woman bent to move her baby in the car seat and experienced sudden, severe pain from 5 spontaneous vertebral compression fractures. Genomic screen was negative but she had mild ankylosing spondylitis previously well controlled on etanercept. She was vegetarian with a high phytate intake. A lactation consultant had advised her to pump and discard milk between feeds, leading her to believe she produced twice as much milk as her baby ingested. She presented with a LS Z score of -3.6 and a TH Z score of -1.6. After 6 mo postweaning, she was treated with teriparatide (14 mo intermittently over 18 mo) and ultimately achieved a 50% increase in LS bone density and an 8% increase in TH bone density. Her fragility is explained by normal lactational bone loss amplified by excessive milk production and phytate-induced impairment of intestinal calcium absorption, ankylosing spondylitis, and the bend-and-lift maneuver. The marked increase in bone density resulted from the combined effects of spontaneous recovery and pharmacotherapy. Spontaneous recovery of bone mass and strength should occur during 12 mo after weaning in all women, including those who have fractured.


Asunto(s)
Fracturas por Compresión , Osteoporosis , Fracturas de la Columna Vertebral , Espondilitis Anquilosante , Humanos , Embarazo , Femenino , Lactancia Materna , Ácido Fítico/farmacología , Ácido Fítico/uso terapéutico , Fracturas de la Columna Vertebral/tratamiento farmacológico , Osteoporosis/diagnóstico por imagen , Osteoporosis/tratamiento farmacológico , Lactancia , Densidad Ósea
5.
Adv Healthc Mater ; 13(4): e2302058, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37972607

RESUMEN

Medical device-associated infections (MDAI) caused by planktonic pathogens are of serious concern worldwide due to the emergence of drug resistance resulting from continuous overuse or misuse of antibiotics. Therefore, the design of non-antibiotics-based treatment for MDAI is of crucial importance. Black phosphorus (BP), a novel 2D material, has recently received much attention owing to its remarkable physical, chemical, mechanical, and functional features. However, the intricacy of the fabrication process has severely hampered the development of BP in prospective applications. In this study, a simple and eco-friendly liquid-phase exfoliation method of phytic acid (PA)-promoted exfoliation of BP nanosheets (PA@BP NSs) is developed for their potential application in antibacterial photothermal therapy. To impart the antimicrobial effects, the polydimethylsiloxane surfaces are functionalized with quaternized polymer (polyquaternium-2 or PQ) and PA@BP NSs, leading to the formation of PA-BP-PQ composite coatings. In addition to the contact-killing antibacterial effect of the cationic PQ, the PA-BP-PQ coating exhibits remarkable near-infrared irradiation-triggered bactericidal effects with low cytotoxicity both in vitro and in vivo. This study proposes a simple liquid-phase exfoliation technique for the fabrication of BP NSs and a one-step approach for the construction of PA-BP-PQ composite coatings for bi-modal (contact-killing and photothermal) antimicrobial therapy.


Asunto(s)
Indanos , Fósforo , Ácido Fítico , Ácido Fítico/farmacología , Fósforo/farmacología , Fototerapia/métodos , Antibacterianos/farmacología
6.
Chem Biol Interact ; 387: 110818, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38000455

RESUMEN

Hyperglycaemia causes impairment of osteogenic differentiation and accelerates stem cell senescence, resulting in weakened osteogenesis and disordered bone metabolism. Phytic acid (PA) is an antioxidant that is reportedly beneficial to bone homeostasis. The present study aims to clarify how PA affects the osteogenic capacity and cellular senescence of bone marrow mesenchymal stem cells (BMSCs) exposed to high-glucose environments, as well as the potential molecular mechanisms. Our results indicate that osteogenic differentiation in BMSCs cultivated in high-glucose conditions is enhanced by PA, as evidenced by increased alkaline phosphatase activity and staining, Alizarin Red S staining, osteogenic marker in in vitro studies, and increased osteogenesis in animal experiments. PA also prevented high-glucose-induced senescence of BMSCs, as evidenced by the repression of reactive oxygen species production, senescence-associated ß-galactosidase staining, and P21 and P53 expression. Furthermore, it was found that PA rescued the high-glucose-inhibited expression of phosphorylated extracellular regulated protein kinases (p-ERK). The inhibition of ERK pathway by the specific inhibitor PD98059 blocked the PA-enhanced osteogenesis of BMSCs and promoted cell senescence. Our results revealed that PA enhances osteogenic differentiation and inhibits BMSC senescence in a high-glucose environment. In addition, the activation of the ERK pathway seems to mediate the beneficial effects of PA. The findings provide novel insights that could facilitate bone regeneration in patients with diabetes.


Asunto(s)
Células Madre Mesenquimatosas , Osteogénesis , Animales , Humanos , Ácido Fítico/farmacología , Ácido Fítico/metabolismo , Sistema de Señalización de MAP Quinasas , Diferenciación Celular , Glucosa/metabolismo , Células Cultivadas , Células de la Médula Ósea
7.
Cancer Lett ; 582: 216591, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38097134

RESUMEN

Oxaliplatin is an important initial chemotherapy benefiting advanced-stage colorectal cancer patients. Frustratingly, acquired oxaliplatin resistance always occurs after sequential chemotherapy with diverse antineoplastic drugs. Therefore, an exploration of the mechanism of oxaliplatin resistance formation in-depth is urgently needed. We generated oxaliplatin-resistant colorectal cancer models by four representative compounds, and RNA-seq revealed that oxaliplatin resistance was mainly the result of cells' response to stimulus. Moreover, we proved persistent stimulus-induced endoplasmic reticulum stress (ERs) and associated cellular senescence were the core causes of oxaliplatin resistance. In addition, we screened diverse phytochemicals for ER inhibitors in silico, identifying inositol hexaphosphate (IP6), whose strong binding was confirmed by surface plasmon resonance. Finally, we confirmed the ability of IP6 to reverse colorectal cancer chemoresistance and investigated the mechanism of IP6 in the inhibition of diphthamide modification of eukaryotic elongation factor 2 (eEF2) and PERK activation. Our study demonstrated that oxaliplatin resistance contributed to cell senescence induced by persistently activated PERK and diphthamide modification of eEF2 levels, which were specifically reversed by combination therapy with IP6.


Asunto(s)
Neoplasias Colorrectales , Histidina/análogos & derivados , Ácido Fítico , Humanos , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Ácido Fítico/farmacología , Ácido Fítico/uso terapéutico , Factor 2 de Elongación Peptídica/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética
8.
Am J Rhinol Allergy ; 38(2): 116-122, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38105576

RESUMEN

BACKGROUND: COVID-19 has been associated with olfactory disturbances in many infected patients. The increase in calcium levels in nasal secretions plays an essential role in the olfactory process with a desensitizing effect on olfactory receptor neurons and negative effects on odor transmission. Calcium chelating agents have the ability to bind calcium in nasal mucus and prevent the negative effects associated with calcium increase. OBJECTIVES: The aim of this work is to demonstrate the intra-nasal topical application of sodium phytate, an environmentally friendly, non-harmful calcium chelating agent, to reduce the adverse effects of calcium on olfactory function and improve olfactory dysfunction according to COVID-19. METHODS: Fifty-two patients with a previous COVID-19 and olfactory dysfunction lasting longer than 90 days were enrolled in a prospective, randomized, blinded, controlled clinical trial. Patients were divided into two equal groups: 26 patients received nasal spray containing 0.9% sodium chloride and 26 patients received nasal spray containing 1% sodium phytate. Olfactory function was measured before treatment and 1 month later using the Sniffin' Sticks test. Calcium content of nasal secretions was determined before and after treatment with an ion-selective electrode. RESULTS: A significant improvement from anosmia to hyposmia was demonstrated after the use of sodium phytate compared with no improvement after the use of sodium chloride. In addition, a decrease in the level of calcium in nasal secretions was observed after the use of sodium phytate. CONCLUSION: Sodium phytate has benefit role on improving the olfactory function after COVID-19.


Asunto(s)
COVID-19 , Trastornos del Olfato , Humanos , Calcio/metabolismo , Quelantes/farmacología , Quelantes/uso terapéutico , Moco , Rociadores Nasales , Ácido Fítico/farmacología , Ácido Fítico/uso terapéutico , Estudios Prospectivos , Olfato/fisiología , Cloruro de Sodio/uso terapéutico
9.
PLoS One ; 18(12): e0295612, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38096253

RESUMEN

OBJECTIVES: This study evaluated phytic acid (IP6) effect on the viability, alkaline phosphatase (ALP) activity and calcium release of human periodontal ligament (HPDL) cells in optimal (OGL) and elevated glucose level (EGL) in cell culture media. MATERIALS AND METHODS: Cells were seeded in OGL (1000mg/L) or EGL (4500 mg/L) media. IP6 was added at 0.005%, 0.01% or 0.02% concentrations for 24 or 48h, and XTT assay was performed. Cell differentiation and calcium release in presence of 0.02% IP6 in OGL or EGL in non-osteogenic or osteogenic media were analyzed using ALP assay and alizarin red staining, respectively. RESULTS: In OGL, IP6 enhanced the viability of the cells at both exposure times (P<0.05). However, IP6 lowered the viability of the cells with the presence of EGL compared to the control at both exposure times, except for 0.02% IP6 which showed comparable viability to the control at 48 h. In OGL and EGL, ALP activity of the cells was not affected by the presence of IP6 in non-osteogenic media; however, in osteogenic media IP6 lowered the ALP activity. Meanwhile, calcium release was the highest with IP6 within osteogenic media of EGL. CONCLUSIONS: IP6 effects on the HPDL cells were dependent on IP6 concentration, time of exposure, glucose levels and the osteogenic condition of the media. CLINICAL RELEVANCE: This study gives insights on the potential therapeutic effect of IP6 as adjunctive periodontal therapy in patients with diabetes.


Asunto(s)
Ligamento Periodontal , Ácido Fítico , Humanos , Ácido Fítico/farmacología , Calcio/farmacología , Osteogénesis , Células Cultivadas , Diferenciación Celular , Fibroblastos , Glucosa/farmacología , Proliferación Celular , Fosfatasa Alcalina
10.
Int J Mol Sci ; 24(21)2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37958674

RESUMEN

Hyaline articular cartilage has unique physiological, biological, and biomechanical properties with very limited self-healing ability, which makes the process of cartilage regeneration extremely difficult. Therefore, research is currently focused on finding new and potentially better treatment options. The main objective of this in vivo study was to evaluate a novel biocement CX consisting of tetracalcium phosphate-monetit biocement hardened with a phytic acid-phytase mixture for the regeneration of osteochondral defects in sheep. The results were compared with tetracalcium phosphate-monetit biocement with classic fast-setting cement systems and untreated defects. After 6 months, the animals were sacrificed, and the samples were evaluated using macroscopic and histologic methods as well as X-ray, CT, and MR-imaging techniques. In contrast to the formation of fibrous or fibrocartilaginous tissue on the untreated side, treatment with biocements resulted in the formation of tissue with a dominant hyaline cartilage structure, although fine fibres were present (p < 0.001). There were no signs of pathomorphological changes or inflammation. Continuous formation of subchondral bone and hyaline cartilage layers was present even though residual biocement was observed in the trabecular bone. We consider biocement CX to be highly biocompatible and suitable for the treatment of osteochondral defects.


Asunto(s)
6-Fitasa , Cartílago Articular , Animales , Ovinos , Ácido Fítico/farmacología , Cartílago Articular/patología , Cicatrización de Heridas
11.
Br Poult Sci ; 64(6): 763-772, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37747291

RESUMEN

1. Phytic acid (PA) is an antinutritional factor in poultry diets. The effect of high dietary PA in chicken diets might be exacerbated when the particle size of oyster shell (OS) is too fine. Thus, this study investigated the hypothesis that high PA with fine OS particle size would impair growth in broilers.2. Two hundred and eighty Cobb 500 broilers were assigned to four diets in a 2 × 2 factorial arrangement in a CRD. The factors were PA (low or high) and OS particle size (fine or coarse) in starter, grower and finisher diets. Data collected were performance, Ca digestibility, gastrointestinal pH and bone traits.3. On d 21, high PA increased intake (P < 0.05), gain (P = 0.099) and body weight (BW; P = 0.093) compared to low PA. On d 42, high PA increased BW (P = 0.086) and gain (P = 0.089) compared to low PA. High PA increased intake (P = 0.063), BW (P = 0.054) and gain (P = 0.056) compared to low PA on d 56. High PA improved liveability on d 56 (P < 0.05) compared to low PA. In birds fed coarse OS, crop and ileal pH were reduced (P < 0.05) by high PA on d 28. The OS × PA interaction was observed for ileal pH (P < 0.05) on d 56, where in birds fed coarse OS, low PA increased ileal pH. Fine OS increased crop (P = 0.056) and proventriculus pH (P < 0.05) on d 56. There were no treatment effects on calcium digestibility. In birds fed fine OS, high PA decreased the BS (P < 0.05).4. Overall, the study showed that a combination of high PA and coarse OS particle size improves the production performance of broilers, while low PA and coarse OS improve their bone health.


Asunto(s)
Pollos , Ostreidae , Animales , Calcio , Ácido Fítico/farmacología , Tamaño de la Partícula , Digestión , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Carbonato de Calcio , Calcio de la Dieta , Dieta/veterinaria , Concentración de Iones de Hidrógeno
12.
Int J Biol Macromol ; 253(Pt 4): 126905, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37729982

RESUMEN

In this study, chitosan (CS) and phytic acid (PA) were employed as raw materials to synthesize a range of chitosan-phytic acid complexes (CP) with different ratios (CS:PA = 12:1, 9:1, 6:1, 3:1, 1:1). The structures and elemental compositions of the compounds were characterized using Fourier-Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy (SEM-EDS). The thermal stability of the synthesized materials was analyzed using a Thermogravimetric Analyzer (TG). Electrochemical testing was conducted to explore the corrosion inhibition effect of the modified inhibitors with varying ratios on Q235 steel in 3.5 wt% NaCl solution. Additionally, Scanning Electron Microscopy (SEM) was utilized to investigate the surface morphology of the immersed samples. When the CS:PA ratio was 3:1, CP exhibited an impressive corrosion inhibition efficiency of 94.9 %. Furthermore, the antimicrobial properties of CP were evaluated using the colony plate counting method. At a CS:PA ratio of 1:1, CP demonstrated the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) at 0.1250 % and 0.5000 %, respectively. This research introduces a novel green corrosion inhibitor capable of simultaneously reducing the electrochemical corrosion of Q235 while inhibiting biocorrosion, avoiding the antagonistic effects arising from the simultaneous use of biocides and corrosion inhibitors in the system.


Asunto(s)
Quitosano , Ácido Fítico , Ácido Fítico/farmacología , Quitosano/farmacología , Quitosano/química , Corrosión , Espectroscopía Infrarroja por Transformada de Fourier , Antibacterianos/farmacología , Antibacterianos/química
13.
Environ Toxicol Pharmacol ; 102: 104241, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37562547

RESUMEN

The use of in vivo models to assess nephrotoxicity has faced ethical limitations. A viable alternative is the ex vivo model that combines the 3 R principles with the preservation of tissue histology. Here, we established a gentamicin nephrotoxicity model using pigs` kidney explants and investigated the effect of phytic acid (IP6) against gentamicin- induced nephrotoxicity. A total of 360 kidney explants were divided into control, gentamicin (10 mM), IP6 (5 mM), and gentamicin+IP6 groups. The activity of gammaglutamyltransferase (GGT), creatinine levels, histological assessment, oxidative stress, and inflammatory cytokine expression were analyzed. Exposure to gentamicin induced an increase in GGT activity, creatinine levels, lesion score, lipoperoxidation and IL-8 expression. Explants exposed to IP6 remained like the control. The addition of IP6 to gentamicin prevented tissue damage, increasing the antioxidant status and gene expression of IL-10. This model proved to be an adequate experimental approach for identifying nephrotoxins and potential products to modulate the toxicity.


Asunto(s)
Enfermedades Renales , Insuficiencia Renal , Animales , Porcinos , Ácido Fítico/farmacología , Ácido Fítico/uso terapéutico , Ácido Fítico/metabolismo , Creatinina , Riñón , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Gentamicinas/toxicidad , Estrés Oxidativo , Enfermedades Renales/patología
14.
ACS Biomater Sci Eng ; 9(8): 4720-4734, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37491189

RESUMEN

Hyperglycemia in patients with diabetes affect osteoblast function, leading to abnormal bone metabolism and implant failure. Adequate bone volume surrounding an implant is essential for osseointegration, which can be improved by implant surface modifications. In this study, titanium surfaces were hydrothermally treated with a mixture of phytic acid (PA) and calcium hydroxide to produce a calcium-decorated surface. The control group comprised pure titanium with a sandblasted/acid-etched (SLA) surface. The elemental composition, hydrophilicity, surface roughness, and morphology of the titanium surfaces were examined. Evaluation of in vitro osteogenic differentiation ability in a high-glucose environment using alkaline phosphatase (ALP) staining, ALP activity assays, Alizarin Red S staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and immunofluorescence staining revealed that Ca-PA-modified SLA titanium surfaces can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Evaluation of oxidative stress and aging using reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and ß-galactosidase staining revealed that Ca-PA-modified SLA titanium surfaces can reduce ROS production and ameliorate oxidative stress damage in hBMSCs. In vivo assessment of osteogenesis in a diabetic rat model revealed that Ca-PA coating promotes peri-implant osseointegration. Ca-PA-modified SLA titanium surface is a candidate for improving implant osseointegration in patients with diabetes.


Asunto(s)
Diabetes Mellitus , Osteogénesis , Humanos , Ratas , Animales , Especies Reactivas de Oxígeno , Ácido Fítico/farmacología , Titanio/farmacología , Proliferación Celular , Senescencia Celular , Oseointegración , Glucosa
15.
Biol Pharm Bull ; 46(8): 1145-1151, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37286513

RESUMEN

Inositol hexaphosphate (IP6), a widely found natural bioactive substance in grains, effectively inhibits the progression of colorectal cancer (CRC) when used in combination with inositol (INS). We previously showed that supplementation of IP6 and INS upregulated the claudin 7 gene in orthotropic CRC xenografts in mice. The aim of this study was to elucidate the role of claudin 7 in the inhibition of CRC metastasis by IP6 and INS, and explore the underlying mechanisms. We found that IP6, INS and their combination inhibited the epithelial-mesenchymal transition (EMT) of colon cancer cell lines (SW480 and SW620), as indicated by upregulation of claudin 7 and E-cadherin, and downregulation of N-cadherin. The effect of IP6 and INS was stronger compared to either agent alone (combination index < 1). Furthermore, the silencing of the claudin 7 gene diminished the anti-metastatic effects of IP6 and INS on SW480 and SW620 cells. Consistent with in vitro findings, the combination of IP6 and INS suppressed CRC xenograft growth in a mouse model, which was neutralized by claudin 7. Taken together, the combination of IP6 and INS can inhibit CRC metastasis by blocking EMT of tumor cells through upregulation of claudin 7.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Ratones , Animales , Neoplasias Colorrectales/metabolismo , Ácido Fítico/farmacología , Ácido Fítico/uso terapéutico , Inositol/farmacología , Inositol/uso terapéutico , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Claudinas/genética
16.
Biomolecules ; 13(6)2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-37371493

RESUMEN

Phosphorylated inositol hexaphosphate (IP6) is a naturally occurring carbohydrate, and its parent compound, myoinositol (Ins), is abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate essential cellular functions. IP6 has profound modulation effects on macrophages, which warrants further research on the therapeutic benefits of IP6 for inflammatory diseases. Here, we review IP6 as a promising compound that has the potential to be used in various areas of dentistry, including endodontics, restorative dentistry, implantology, and oral hygiene products, due to its unique structure and characteristic properties. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anti-inflammatory effect associated with preventing and suppressing the progression of chronic dental inflammatory diseases. IP6 in dentistry is now substantial, and this narrative review presents and discusses the different applications proposed in the literature and gives insights into future use of IP6 in the fields of orthodontics, periodontics, implants, and pediatric dentistry.


Asunto(s)
Inositol , Ácido Fítico , Niño , Humanos , Inositol/farmacología , Inositol/uso terapéutico , Ácido Fítico/farmacología , Ácido Fítico/uso terapéutico
17.
Microbiol Spectr ; 11(3): e0026723, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37191582

RESUMEN

Root canal infections are associated with biofilms and are treated with chemical irrigants with a high success rate. However, treatment failure does arise, which is attributed primarily to resistance exhibited by biofilms. Currently used irrigants in root canal treatment have disadvantages, and there is therefore a need for more biocompatible alternatives with antibiofilm properties to reduce root canal treatment failure and complications. The aim of this study was to evaluate the in vitro antibiofilm properties of phytic acid (IP6), which is a potential alternative treatment agent. Single- and dual-species biofilms of Enterococcus faecalis and Candida albicans were developed on the well surfaces of 12-well plates and on hydroxyapatite (HA) coupons, and then exposed to IP6. In addition, selected HA coupons were preconditioned with IP6 before biofilm development. IP6 demonstrated bactericidal effects and altered the metabolic activity of biofilm cells. Confocal laser-scanning microscopy showed that IP6 caused significant and rapid reduction in live biofilm cells. At sublethal concentrations, IP6 did not alter the expression of tested virulence genes except for C. albicans hwp1, the expression of which was upregulated but not reflected by a change in hyphal transformation. IP6-preconditioned HA coupons led to extensive inhibition of dual-species biofilm formation. The results of this study highlight for the first time the antibiofilm inhibitory properties of IP6 and the potential for its exploitation in several clinical applications. IMPORTANCE Root canal infections are biofilm associated, and despite mechanical and chemical treatment procedures, infection recurrence occurs, and this is likely due to the high tolerance of associated biofilms to antimicrobials. The currently used treatment agents have several disadvantages, which necessitates the search for new improved agents. In this study, the natural chemical phytic acid was found to exhibit antibiofilm activity against established mono and dual mature biofilms over a short contact time. Most importantly, phytic acid was found to cause significant inhibition of dual-species biofilm formation when used as a surface preconditioning agent. The findings of this study identified a novel use of phytic acid as a potential antibiofilm agent that can be used in several clinical applications.


Asunto(s)
Antiinfecciosos , Ácido Fítico , Ácido Fítico/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Candida albicans , Biopelículas
18.
Adv Sci (Weinh) ; 10(16): e2300354, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37026671

RESUMEN

Surface modification plays a pivotal role in tailoring the functionalities of a solid material. Introduction of antimicrobial function on material surfaces can provide additional protection against life-threatening bacterial infections. Herein, a simple and universal surface modification method based on surface adhesion and electrostatic interaction of phytic acid (PA) is developed. PA is first functionalized with Prussian blue nanoparticles (PB NPs) via metal chelation and then conjugates with cationic polymers (CPs) through electrostatic interaction. With the aid of surface adherent PA and gravitation effect, the as-formed PA-PB-CP network aggregates are deposited on the solid materials in a substrate-independent manner. Synergistic bactericidal effects of "contact-killing" induced by the CPs and localized photothermal effect caused by the PB NPs endow the substrates with strong antibacterial performance. Membrane integrity, enzymatic activity, and metabolism function of the bacteria are disturbed in contact with the PA-PB-CP coating under near-infrared (NIR) irradiation. The PA-PB-CP modified biomedical implant surfaces exhibit good biocompatibility and synergistic antibacterial effect under NIR irradiation, and eliminate the adhered bacteria both in vitro and in vivo.


Asunto(s)
Nanopartículas , Polímeros , Polímeros/farmacología , Ácido Fítico/farmacología , Antibacterianos/farmacología
19.
Biotechnol Appl Biochem ; 70(5): 1690-1706, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37042496

RESUMEN

Phosphorous actively participates in numerous metabolic and regulatory activities of almost all living organisms including animals and humans. Therefore, it is considered as an essential macronutrient required supporting their proper growth. On contrary, phytic acid (PA), an antinutritional substance, is widely known for its strong affinity to chelate essential mineral ions including PO4 3- , Ca2+ , Fe2+ , Mg2+ , and Zn2+ . Being one the major reservoir of PO4 3- ions, PA has great potential to bind PO4 3- ions in diverse range of foods. Once combined with P, PA transforms into an undigested and insoluble complex namely phytate. Produced phytate leads to a notable reduction in the bioavailability of P due to negligible activity of phytases in monogastric animals and humans. This highlights the importance and consequent need of enhancement of phytase level in these life forms. Interestingly, phytases, catalyzing the breakdown of phytate complex and recycling the phosphate into ecosystem to its available form, have naturally been reported in a variety of plants and microorganisms over past few decades. In pursuit of a reliable solution, the focus of this review is to explore the keynote potential of bacterial phytases for sustainable management of phosphorous via efficient utilization of soil phytate. The core of the review covers detailed discussion on bacterial phytases along with their widely reported applications viz. biofertilizers, phosphorus acquisition, and plant growth promotion. Moreover, meticulous description on fermentation-based strategies and future trends on bacterial phytases have also been included.


Asunto(s)
6-Fitasa , Ácido Fítico , Humanos , Animales , Ácido Fítico/farmacología , Ácido Fítico/metabolismo , 6-Fitasa/metabolismo , Ecosistema , Fósforo , Fosfatos
20.
Physiol Plant ; 175(3): e13913, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37043305

RESUMEN

Rice with a black-colored pericarp (hereafter, black rice) is well-known as an antioxidant-rich food, but a high grain phytic acid (PA) concentration affects its nutritional quality. However, phytic acid helps improve seedling vigor, which is crucial for enhancing subsequent plant growth. This study investigated the effect of seed phytic acid concentration in black rice on seedling vigor compared to the effects on white rice. In the first experiment, three phytic acid concentrations in the seeds of black rice, low (LPA, 15.5 mg g-1 per seed), medium (MPA, 24.7 mg g-1 per seed), and high (HPA, 35.4 mg g-1 per seed) were tested for seedling vigor in phosphorus-deficient soils. The HPA seedlings showed substantially increased seedling vigor and shoot P uptake due to early root development and enhanced physiological processes. LPA grown seedlings showed increased ethylene production in response to P stress, which is the main physiological mechanism modulating seedling growth under P stress conditions. In the second experiment, the three phytic acid concentrations in black and white rice seeds were tested under low and high soil P conditions. Again, LPA seedlings showed significantly reduced seedling vigor in both rice varieties in P-deficient soils. Interestingly, seed phytic acid and external P application had an additive effect on seedling vigor, suggesting that the combined effect further improved seedling growth. Our results reveal that black rice seeds with a HPA concentration can be used as a seed source for planting in P-deficient ecosystems for rice plants as they can increase seedling vigor and subsequent growth, thus reducing dependence on finite P resources.


Asunto(s)
Oryza , Plantones , Ácido Fítico/farmacología , Fósforo/farmacología , Suelo , Disponibilidad Biológica , Ecosistema , Semillas , Germinación
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