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1.
AAPS PharmSciTech ; 25(5): 106, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724834

ABSTRACT

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.


Subject(s)
Antifungal Agents , Biofilms , Candida albicans , Chitosan , Microbial Sensitivity Tests , Nanoparticles , Phytic Acid , Chitosan/chemistry , Biofilms/drug effects , Nanoparticles/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/administration & dosage , Animals , Candida albicans/drug effects , Mice , Microbial Sensitivity Tests/methods , Phytic Acid/pharmacology , Phytic Acid/administration & dosage , Phytic Acid/chemistry , Female , Candidiasis/drug therapy , Particle Size , Drug Carriers/chemistry , Cross-Linking Reagents/chemistry , Cytokines/metabolism
2.
Parasite Immunol ; 46(5): e13040, 2024 May.
Article in English | MEDLINE | ID: mdl-38801355

ABSTRACT

Cystic echinococcosis is caused by the tissue-dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is that this larva is protected by the acellular laminated layer (LL). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite's vicinity. The potential of LL particles to induce inflammation in vivo has not been specifically analysed. It is not known how each of its two major components, namely highly glycosylated mucins and calcium inositol hexakisphosphate (InsP6) deposits, impacts inflammation induced by the LL as a whole. In this work, we show that LL particles injected intraperitoneally cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as the disappearance of resident (large peritoneal) macrophages. Strikingly, the absence of calcium InsP6 enhanced the recruitment of all the inflammatory cell types analysed. In contrast, oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils. The carbohydrate-oxidised particles caused cell influx nonetheless, which may be explained by possible receptor-independent effects of LL particles on innate immune cells, as suggested by previous works from our group. In summary, LL particles can induce acute inflammatory cell recruitment partly dependent on its mucin glycans, and this recruitment is attenuated by the calcium InsP6 component.


Subject(s)
Echinococcus granulosus , Phytic Acid , Animals , Echinococcus granulosus/immunology , Phytic Acid/pharmacology , Phytic Acid/metabolism , Echinococcosis/immunology , Echinococcosis/parasitology , Inflammation , Neutrophils/immunology , Mucins/metabolism , Mice , Macrophages/immunology , Macrophages/metabolism , Eosinophils/immunology , Female , Larva/immunology
3.
ACS Appl Bio Mater ; 7(5): 3283-3294, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38727030

ABSTRACT

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Gold , Materials Testing , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Phytic Acid , Staphylococcus aureus , Gold/chemistry , Gold/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Metal Nanoparticles/chemistry , Phytic Acid/chemistry , Phytic Acid/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Animals , Surface Properties , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cations/chemistry , Cations/pharmacology , Polymers/chemistry , Polymers/pharmacology , Titanium/chemistry , Titanium/pharmacology
4.
ACS Nano ; 18(21): 13528-13537, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38747549

ABSTRACT

Dental caries is a widespread oral disease that poses a significant medical challenge. Traditional caries prevention methods, primarily the application of fluoride, often fall short in effectively destroying biofilms and preventing enamel demineralization, thereby providing limited efficacy in halting the progression of caries over time. To address this issue, we have developed a green and cost-effective synergistic strategy for the prevention of dental caries. By combining natural sodium phytate and chitosan, we have created chitosan-sodium phytate nanoparticles that offer both the antimicrobial properties of chitosan and the enamel demineralization-inhibiting capabilities of sodium phytate. In an ex vivo biofilm model of human teeth, we found that these nanoparticles effectively prevent biofilm buildup and acid damage to the mineralized tissue. Additionally, topical treatment of dental caries in rodent models has shown that these nanoparticles effectively suppress disease progression without negatively impacting oral microbiota diversity or causing harm to the gingival-mucosal tissues, unlike traditional prevention methods.


Subject(s)
Biofilms , Chitosan , Dental Caries , Nanoparticles , Phytic Acid , Dental Caries/prevention & control , Chitosan/chemistry , Chitosan/pharmacology , Humans , Nanoparticles/chemistry , Phytic Acid/chemistry , Phytic Acid/pharmacology , Phytic Acid/administration & dosage , Animals , Biofilms/drug effects , Streptococcus mutans/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Mice
5.
Int J Biol Macromol ; 269(Pt 1): 132080, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705314

ABSTRACT

Theranostic antibacterial wound dressing is highly recommended in practical applications. The conventional methods of integrating diagnostic and therapeutic functions have the disadvantages of complicated preparation, mutual interference, inability to effectively broad spectrum antibacterial property, and easy to induce drug-resistant bacteria. Herein, a pH and light-responsive theranostic antibacterial hydrogel is developed by biopolymers polyvinyl alcohol (PVA) and polyaniline (PANI), and cross-linking with phytic acid (PA), which is widely present in rice bran. The biological polymer-based conductive hydrogel enables timely diagnosis and photothermal sterilization in-situ for wound healing. Because PANI is highly sensitive to pH changes in the bacterial microenvironment, the hydrogel can detect bacterial infections at concentrations as low as 103 CFU/mL. Subsequently, PANI absorbs near-infrared light to achieve on-demand exothermic sterilization (under 808 nm irradiation for 20 min, the killing ratios for Staphylococcus aureus and Escherichia coli reached almost 100 %). In addition, the hydrogel can monitor the intensity of joint movement to avoid wound re-tearing sensitively. In vitro cytotoxicity and hemocompatibility experiments and in vivo full-thickness infected wound model indicate that the hydrogel has good biocompatibility, antibacterial ability, and can accelerate the wound healing effectively. This work will promote the development of wearable electronic devices and precision medicine.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Hydrogels , Oryza , Phytic Acid , Staphylococcus aureus , Wound Healing , Phytic Acid/chemistry , Phytic Acid/pharmacology , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Oryza/chemistry , Staphylococcus aureus/drug effects , Animals , Escherichia coli/drug effects , Biopolymers/chemistry , Biopolymers/pharmacology , Theranostic Nanomedicine , Mice , Humans , Polyvinyl Alcohol/chemistry , Aniline Compounds/chemistry , Aniline Compounds/pharmacology
6.
Int J Biol Macromol ; 269(Pt 2): 132135, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719000

ABSTRACT

Here, a novel multifunctional coating containing bio-based phytic acid (PA), L-glutamic acid (L-Glu), and trimesoyl chloride (TMC) is constructed by a simple soaking strategy, giving cotton fabrics excellent flame retardancy, washability, and antibacterial properties. The coating layer on the cotton surface was prepared via the electrostatic and hydrogen bonding between PA and L-Glu, accompanied by the interface polymerization between PA, L-Glu, and TMC. Among them, the limiting oxygen index value of the treated cotton fabrics (C2 and C2-TMC) was as high as 40 %. During the vertical flammability test, both C2 and C2-TMC cotton showed self-extinguished behavior with a short damaged length (≤50 mm). Remarkably, the LOI of C2-TMC sustained a high value (30 %) even after 300 laundering cycles, maintaining its self-extinguishing behavior in the vertical combustion test. Additionally, in the cone calorimetry test, peak heat release rate and total heat release of treated cotton were lower than control cotton. Surprisingly, after 30 or 60 laundering cycles, the C2-TMC cotton exhibited excellent antibacterial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans due to the continuous exposure of PA and L-Glu. Moreover, the coating layer on the cotton surface had little impact on the mechanical properties and feel of the fabric.


Subject(s)
Cotton Fiber , Flame Retardants , Phytic Acid , Phytic Acid/chemistry , Phytic Acid/pharmacology , Amino Acids/chemistry , Candida albicans/drug effects , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Textiles , Microbial Sensitivity Tests
7.
Animal ; 18(5): 101135, 2024 May.
Article in English | MEDLINE | ID: mdl-38636148

ABSTRACT

There is a gap in the understanding of the relationship between dietary phytate levels and the relative efficacy of phytase to improve amino acid (AA) digestibility in pigs and chickens. Two experiments were conducted to investigate the effect of exogenous phytase on standardized ileal digestibility (SID) of AA and the apparent ileal digestibility (AID) of P in both standard- (SP) and high-phytate (HP) diets for broilers and swine. There were either 40 cages of Cobb 500 male broilers or 10 crossbred barrows (35 kg) fitted with ileal T-cannulas. Both studies were allotted to five dietary treatments (8 replicates). Treatments consisted of four corn-soybean meal-based diets arranged in a 2 × 2 factorial of standard or high phytate and exogenous phytase at 0 or 1 000 phytase units (FYT)/kg; and one N-free diet. Birds were fed a common starter diet from d 0 to 20 and fed experimental diets from d 20 to 25. Birds were euthanized on d 25 via CO2 asphyxiation, and digesta were collected from the terminal ileum. Pigs were fed for a total of four 7-d periods, where digesta were collected on d 6 and 7 of each period. Diet and digesta samples were analyzed for DM, N, Ti, AA, and P to determine AA and P digestibility. The SID of AA was determined by correcting the AID of AA for the basal endogenous losses estimated using the N-free diet. Main effects of the diet type (standard or HP) and phytase (0 or 1 000 FYT/kg), and the interaction of diet type and phytase were evaluated. For both experiments, the HP diets produced lower SID of AA compared to the SP (P < 0.001). For broilers, there was a phytase effect (P < 0.001) for the SID of all AAs evaluated regardless of the diet type. For pigs, phytase improved (P < 0.05) the SID of Met, Lys, Cys, Glu and Ser and tended to improve (P < 0.10) Arg, Leu, Thr, and Tyr. There were no significant interactions for either experiment. For both experiments, AID of P was lower for the HP diets (P < 0.01), and phytase produced greater AID of P for both diet types (P < 0.01). These data indicate that phytase greatly improves the digestibility of P for broilers and pigs and has the ability to significantly increase the digestibility of amino acids for these animals, regardless of the dietary phytate P.


Subject(s)
6-Phytase , Animal Feed , Animal Nutritional Physiological Phenomena , Chickens , Diet , Digestion , Ileum , Phytic Acid , Animals , 6-Phytase/administration & dosage , 6-Phytase/pharmacology , Chickens/physiology , Chickens/metabolism , Animal Feed/analysis , Phytic Acid/metabolism , Phytic Acid/administration & dosage , Phytic Acid/pharmacology , Male , Digestion/drug effects , Diet/veterinary , Animal Nutritional Physiological Phenomena/drug effects , Ileum/metabolism , Swine/physiology , Amino Acids/metabolism , Dietary Supplements/analysis
8.
Biochem Pharmacol ; 222: 116118, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38467376

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Experimental , Mesenchymal Stem Cells , MicroRNAs , Rats , Animals , Osteogenesis , MicroRNAs/metabolism , Phytic Acid/pharmacology , Phytic Acid/metabolism , Diabetes Mellitus, Experimental/metabolism , Cell Differentiation , Mesenchymal Stem Cells/metabolism , Glucose/pharmacology , Glucose/metabolism , Bone Marrow Cells/metabolism , Cells, Cultured
9.
ACS Chem Neurosci ; 15(6): 1157-1168, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38445956

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Peripheral Nervous System Diseases , Humans , Antineoplastic Agents/toxicity , Cisplatin/toxicity , Ganglia, Spinal , Membrane Potential, Mitochondrial , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/drug therapy , Peripheral Nervous System Diseases/metabolism , Phytic Acid/pharmacology , Phytic Acid/metabolism , Phytic Acid/therapeutic use , Platinum/pharmacology , Platinum/metabolism , Reactive Oxygen Species/metabolism , Sensory Receptor Cells/metabolism
10.
J Bone Miner Res ; 39(3): 197-201, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38477812

ABSTRACT

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.


Subject(s)
Fractures, Compression , Osteoporosis , Spinal Fractures , Spondylitis, Ankylosing , Humans , Pregnancy , Female , Breast Feeding , Phytic Acid/pharmacology , Phytic Acid/therapeutic use , Spinal Fractures/drug therapy , Osteoporosis/diagnostic imaging , Osteoporosis/drug therapy , Lactation , Bone Density
11.
Adv Healthc Mater ; 13(4): e2302058, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37972607

ABSTRACT

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.


Subject(s)
Indans , Phosphorus , Phytic Acid , Phytic Acid/pharmacology , Phosphorus/pharmacology , Phototherapy/methods , Anti-Bacterial Agents/pharmacology
12.
Chem Biol Interact ; 387: 110818, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38000455

ABSTRACT

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.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Animals , Humans , Phytic Acid/pharmacology , Phytic Acid/metabolism , MAP Kinase Signaling System , Cell Differentiation , Glucose/metabolism , Cells, Cultured , Bone Marrow Cells
13.
Am J Rhinol Allergy ; 38(2): 116-122, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38105576

ABSTRACT

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.


Subject(s)
COVID-19 , Olfaction Disorders , Humans , Calcium/metabolism , Chelating Agents/pharmacology , Chelating Agents/therapeutic use , Mucus , Nasal Sprays , Phytic Acid/pharmacology , Phytic Acid/therapeutic use , Prospective Studies , Smell/physiology , Sodium Chloride/therapeutic use
14.
Cancer Lett ; 582: 216591, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38097134

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms , Histidine/analogs & derivatives , Phytic Acid , Humans , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Phytic Acid/pharmacology , Phytic Acid/therapeutic use , Peptide Elongation Factor 2/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics
15.
PLoS One ; 18(12): e0295612, 2023.
Article in English | MEDLINE | ID: mdl-38096253

ABSTRACT

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.


Subject(s)
Periodontal Ligament , Phytic Acid , Humans , Phytic Acid/pharmacology , Calcium/pharmacology , Osteogenesis , Cells, Cultured , Cell Differentiation , Fibroblasts , Glucose/pharmacology , Cell Proliferation , Alkaline Phosphatase
16.
Int J Mol Sci ; 24(21)2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37958674

ABSTRACT

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.


Subject(s)
6-Phytase , Cartilage, Articular , Animals , Sheep , Phytic Acid/pharmacology , Cartilage, Articular/pathology , Wound Healing
17.
Int J Biol Macromol ; 253(Pt 4): 126905, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37729982

ABSTRACT

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.


Subject(s)
Chitosan , Phytic Acid , Phytic Acid/pharmacology , Chitosan/pharmacology , Chitosan/chemistry , Corrosion , Spectroscopy, Fourier Transform Infrared , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
18.
Br Poult Sci ; 64(6): 763-772, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37747291

ABSTRACT

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.


Subject(s)
Chickens , Ostreidae , Animals , Calcium , Phytic Acid/pharmacology , Particle Size , Digestion , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Calcium Carbonate , Calcium, Dietary , Diet/veterinary , Hydrogen-Ion Concentration
19.
Environ Toxicol Pharmacol ; 102: 104241, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37562547

ABSTRACT

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.


Subject(s)
Kidney Diseases , Renal Insufficiency , Animals , Swine , Phytic Acid/pharmacology , Phytic Acid/therapeutic use , Phytic Acid/metabolism , Creatinine , Kidney , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/metabolism , Gentamicins/toxicity , Oxidative Stress , Kidney Diseases/pathology
20.
ACS Biomater Sci Eng ; 9(8): 4720-4734, 2023 08 14.
Article in English | MEDLINE | ID: mdl-37491189

ABSTRACT

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.


Subject(s)
Diabetes Mellitus , Osteogenesis , Humans , Rats , Animals , Reactive Oxygen Species , Phytic Acid/pharmacology , Titanium/pharmacology , Cell Proliferation , Cellular Senescence , Osseointegration , Glucose
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