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RNA interference (RNAi) is an evolutionarily conserved pathway that defends against viral infections in diverse organisms. Caenorhabditis elegans mutations that enhance RNAi have revealed pathways that may regulate antiviral defense. A genetic screen for C. elegans mutations that fail to up-regulate a defense response reporter transgene detected mutations that enhance RNAi to silence this reporter gene in the inositol polyphosphate multikinase impk-1, the synMuv B gene lin-15B, and the pathogen defense response gene pals-22. Using other assays for enhanced RNAi, we found that the impk-1 alleles and an ippk-1 gene inactivation of a later step in inositol hexaphosphate (IP6) synthesis, and the lin-15B and pals-22 alleles enhance RNAi. IP6 has been known for decades to bind and stabilize human adenosine deaminase that acts on RNA (ADAR) as well as the paralog tRNA editing ADAT. We show that the C. elegans IP6 pathway is also required for mRNA and tRNA editing. Thus, a deficiency in two axes of RNA editing enhances the already potent C. elegans RNAi antiviral defense, suggesting adenosine to inosine RNA editing may normally moderate this siRNA antiviral defense pathway. The C. elegans IP6-deficient mutants are synthetic lethal with a set of enhanced RNAi mutants that act in the polyploid hypodermis to regulate collagen secretion and signaling from that tissue, implicating IP6 signaling especially in this tissue. This enhanced antiviral RNAi response uses the C. elegans RIG-I-like receptor DRH-1 to activate the unfolded protein response (UPR). The production of primary siRNAs, rather than secondary siRNAs, contributes to this activation of the UPR through XBP-1 signaling. The gon-14 and pal-17 mutants that also emerged from this screen act in the mitochondrial defense pathway rather than by enhancing RNAi. [ABSTRACT FROM AUTHOR]

Phytic acid (inositol hexaphosphate/IP6) is a versatile chemical that is abundant in nature and is required for a variety of biological processes. It is harnessed in a wide range of fields, including drug discovery, daily supplies, chemical industries, medicine, and dentistry. IP6 is becoming increasingly popular in dentistry, with promising results. Several properties, such as cariostatic ability, beneficial impact on enamel disintegration, and anti-plaque, anti-tartar, and dental adhesive-forming properties, have been investigated thus far. Due to many constraints in the literature, there was a point in time when IP6 received less attention, which impacted knowledge in this field. Nevertheless, the positive outcomes of the flourishing of IP6 have recently been reconsidered from a number of papers that have improved our understanding of its modes of action in the aforementioned applications. The role of phytic acid in refining the properties and manoeuvring of dental resources is being investigated in novel endeavors in treating diseases of pulp and tissues supporting tooth structure, but to show its novel therapeutic potential, more precisely calibrated clinical trials are needed. This review examines and discusses the various uses proposed in the literature, as well as the applications of IP6 in dentistry.

Phytic acid (inositol hexaphosphate/IP6) is a versatile chemical that is abundant in nature and is required for a variety of biological processes. It is harnessed in a wide range of fields, including drug discovery, daily supplies, chemical industries, medicine, and dentistry. IP6 is becoming increasingly popular in dentistry, with promising results. Several properties, such as cariostatic ability, beneficial impact on enamel disintegration, and anti-plaque, anti-tartar, and dental adhesive-forming properties, have been investigated thus far. Due to many constraints in the literature, there was a point in time when IP6 received less attention, which impacted knowledge in this field. Nevertheless, the positive outcomes of the flourishing of IP6 have recently been reconsidered from a number of papers that have improved our understanding of its modes of action in the aforementioned applications. The role of phytic acid in refining the properties and manoeuvring of dental resources is being investigated in novel endeavors in treating diseases of pulp and tissues supporting tooth structure, but to show its novel therapeutic potential, more precisely calibrated clinical trials are needed. This review examines and discusses the various uses proposed in the literature, as well as the applications of IP6 in dentistry. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the adsorption properties of La-activated biochar for pollutants in a binary coexistence system. Materials and methods: La was impregnated with walnut shells to prepare biochar and orthophosphate (OP) and inositol hexaphosphate (IHP) were adsorbed in the composite system. Results and discussion: At the same concentration (75 mg L−1), the overall phosphorus adsorption performance of biochar treatment (CK + BC) was considerably better than that of gypsum (CK + GP) and zeolite (CK + ZP). The maximum adsorption capacities of OP and IHP were 0.52 and 1.29 mg g−1, respectively. In the binary coexistence system, there is a competition among phosphorus species because of the number of adsorption sites on the surface of adsorbents and the blockage effect of pores. The fitting results of the adsorption kinetics and adsorption isotherm model show that the adsorption of phosphorus species is primarily controlled by chemical action. Conclusions: The adsorption mechanism may include electrostatic attraction, ligand exchange, precipitation, and complexation. [ABSTRACT FROM AUTHOR]

Background: Short bowel syndrome (SBS) has high morbidity and mortality rates, and promoting intestinal adaptation of the residual intestine is a critical treatment. Dietary inositol hexaphosphate (IP6) plays an important role in maintaining intestinal homeostasis, but its effect on SBS remains unclear. This study aimed at investigating the effect of IP6 on SBS and clarified its underlying mechanism. Methods: Forty male Sprague–Dawley rats (3-week-old) were randomly assigned into four groups (Sham, Sham + IP6, SBS, and SBS + IP6 groups). Rats were fed standard pelleted rat chow and underwent resection of 75% of the small intestine after 1 week of acclimation. They received 1 mL IP6 treatment (2 mg/g) or sterile water daily for 13 days by gavage. Intestinal length, levels of inositol 1,4,5-trisphosphate (IP3), histone deacetylase 3 (HDAC3) activity, and proliferation of intestinal epithelial cell-6 (IEC-6) were detected. Results: IP6 treatment increased the length of the residual intestine in rats with SBS. Furthermore, IP6 treatment caused an increase in body weight, intestinal mucosal weight, and IEC proliferation, and a decrease in intestinal permeability. IP6 treatment led to higher levels of IP3 in feces and serum, and higher HDAC3 activity of the intestine. Interestingly, HDAC3 activity was positively correlated with the levels of IP3 in feces (r = 0.49, P = 0.01) and serum (r = 0.44, P = 0.03). Consistently, IP3 treatment promoted the proliferation of IEC-6 cells by increasing HDAC3 activity in vitro. IP3 regulated the Forkhead box O3 (FOXO3)/Cyclin D1 (CCND1) signaling pathway. Conclusion: IP6 treatment promotes intestinal adaptation in rats with SBS. IP6 is metabolized to IP3 to increase HDAC3 activity to regulate the FOXO3/CCND1 signaling pathway and may represent a potential therapeutic approach for patients with SBS.

Colorectal cancer is a prevalent malignant tumor, with liver metastases being the primary cause of death. The combination of inositol hexaphosphate (IP6) and inositol (INS) has been shown to inhibit colorectal cancer metastasis. We identified a correlation between CLDN23 expression and the occurrence of liver metastases in colorectal cancer patients. Following the transfection with the lentiviral vector (LV-CLDN23-RNAi), proteomic analysis of SW620 revealed significant alterations in the occludin, ZO-1, RhoA, and ROCK-1 genes expression by western blotting. We found that both SW620 and SW480 cells showed inhibited proliferation, invasion, and migration ability after the treatment with IP6 and INS. Additionally, this combination upregulated occludin and ZO-1, while downregulated CLDN23, RhoA, ROCK-1, and p-MLC2. In conclusion, the combination of IP6 and INS suppressed the proliferation, invasion, and migration of colorectal cancer cells and regulated CLDN23 expression by enhancing tight junction proteins, such as occludin and ZO1, via the RhoA /ROCK1 pathway.

Phytate is widely distributed in the plant kingdom, and its significance for human nutrition has been often described. Data on phytate is available in very few composition tables, for a limited number of foods and mainly for raw products. With the aim of publishing the first global repository of analytical data on phytate, data on moisture, phytate, zinc, iron and calcium were compiled. Other aspects, such as the analytical method used, biodiversity and processing, were considered, and phytate: mineral ratios were calculated when possible. From a comprehensive literature search, over 250 references were compiled, generating 3377 entries: 39% for raw and 61% for processed foods. Most of the entries were for cereals (35%), followed by legumes (27%) and vegetables (11%). The most common analytical methods used were indirect precipitation (26%) and anion exchange (25%), while separate determination of IPs is the most recommended. The database can be used as a tool for nutrition workers to include into food composition tables and to develop programmes related to mineral deficiencies. These data will be useful for designing diets with enhanced mineral bioavailability and for improving the estimates for nutrient requirements. The database is available at the INFOODS (www.fao.org/infoods/infoods/tables-and-databases/en) and IZiNCG webpages (www.izincg.org).

Simple Summary: The stage of a tumor during cancer intervention is the most crucial factor that determines the treatment regimen. Several bioactive natural compounds have shown potential to inhibit prostate cancer growth and progression; however, there is a dearth of studies that explore their efficacy at different stages of tumorigenesis. This knowledge gap prevents researchers from fully exploiting the anti-cancer potential of these beneficial compounds. Accordingly, our present study focused on explicating the 'stage-specific' efficacy of the bioactive food component 'inositol hexaphosphate (IP6, phytic acid)' against PCa initiation, growth, and progression in the transgenic adenocarcinoma of the mouse prostate TRAMP model. Results indicated that IP6 feeding during initial stages of cancer development prevents progression of prostatic intraepithelial neoplasia lesions to adenocarcinoma, and IP6 feeding during late stage of the disease reduces tumor growth and prevents its progression to advanced stage of the disease. Thus, IP6 intervention is beneficial during all stages of prostate tumorigenesis. Herein, we assessed the stage-specific efficacy of inositol hexaphosphate (IP6, phytic acid), a bioactive food component, on prostate cancer (PCa) growth and progression in a transgenic mouse model of prostate cancer (TRAMP). Starting at 4, 12, 20, and 30 weeks of age, male TRAMP mice were fed either regular drinking water or 2% IP6 in water for ~8–15 weeks. Pathological assessments at study endpoint indicated that tumor grade is arrested at earlier stages by IP6 treatment; IP6 also prevented progression to more advanced forms of the disease (~55–70% decrease in moderately and poorly differentiated adenocarcinoma incidence was observed in advanced stage TRAMP cohorts). Next, we determined whether the protective effects of IP6 are mediated via its effect on the expansion of the cancer stem cells (CSCs) pool; results indicated that the anti-PCa effects of IP6 are associated with its potential to eradicate the PCa CSC pool in TRAMP prostate tumors. Furthermore, in vitro assays corroborated the above findings as IP6 decreased the % of floating PC-3 prostaspheres (self-renewal of CSCs) by ~90%. Together, these findings suggest the multifaceted chemopreventive-translational potential of IP6 intervention in suppressing the growth and progression of PCa and controlling this malignancy at an early stage. [ABSTRACT FROM AUTHOR]

Rationale: Understanding the decomposition of inositol hexaphosphate (phytate), the dominant form of organic phosphorus (OP) in soil, is vital for studying phosphorus (P) cycling in terrestrial ecosystems. However, the lack of multiple stable P isotopes complicates the study of phytate dynamics under natural conditions and over long periods., Methods: A novel method is presented to determine the carbon isotopic composition of inositol in phytate using compound-specific isotope analysis. For this purpose, phytate was extracted from soil and purified via ion exchange chromatography, followed by dephosphorylation, derivatization, and analysis using GC-MS and GC-C-IRMS. Pure compounds were also analyzed to assess protocol efficiency, identify isotopic fractionations, and apply isotopic corrections due to derivatization., Results: Phytate extracted from soil samples was identified using GC-MS chromatograms. Replicate analyses of the pure compounds indicated that the protocol is highly reproducible. The carbon isotopic composition (δ 13 C) showed a high reproducibility, with values varying by less than 0.5‰ and with no detectable isotopic fractionation during sample preparation. The δ 13 C values of phytate in soil samples reflected the dominant vegetation type (C 3 or C 4 ) growing at the study site., Conclusions: This study offers a novel approach of determining δ 13 C values of inositol of phytate in environmental samples, offering new opportunities to investigate and quantify OP dynamics based on stable carbon isotopes., (© 2025 The Author(s). Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

With the development of biomaterials, a hydroxyapatite (HA) bone cement based on chelation has gradually attracted attention. This paper presents an investigation on the micromorphology and mechanical property of HA bone cement prepared by HA powders modified by inositol hexaphosphate (IP6, phytic acid). With the citric acid monohydrate (CA) solution used as setting liquid, scanning electron microscopy (SEM) and universal testing machine were employed to investigate the influence of parameters including concentrations of CA as well as powder–liquid ratio on the properties of HA bone cement. In addition, the setting mechanism of chelating cement was analyzed. The results showed that when CA concentration was more than 20 wt.%, the curing products of IP6/CA dual chelating HA cement contained calcium citrate tetrahydrate and tricalcium phosphate (TCP) besides HA. The compressive strength of dual chelated cement increased with the CA concentration. With 10 000 ppm‐IP6‐HA used as the starting powder, the maximum compressive strength of bone cement prepared with 40 wt.% CA as the setting liquid was up to 57 MPa. Furthermore, the temperature, pH, antibacterial activity measurement, and cell studies in vitro were carried on, suggesting that chelate‐setting HA cement has potential development in orthopedic materials. [ABSTRACT FROM AUTHOR]

The modular Integrator complex is a transcription regulator that is essential for embryonic development. It attenuates coding gene expression via premature transcription termination and performs 3′-processing of non-coding RNAs. For both activities, Integrator requires endonuclease activity that is harbored by an RNA cleavage module consisting of INTS4-9-11. How correct assembly of Integrator modules is achieved remains unknown. Here, we show that BRAT1 and WDR73 are critical biogenesis factors for the human cleavage module. They maintain INTS9-11 inactive during maturation by physically blocking the endonuclease active site and prevent premature INTS4 association. Furthermore, BRAT1 facilitates import of INTS9-11 into the nucleus, where it is joined by INTS4. Final BRAT1 release requires locking of the mature cleavage module conformation by inositol hexaphosphate (IP 6). Our data explain several neurodevelopmental disorders caused by BRAT1, WDR73, and INTS11 mutations as Integrator assembly defects and reveal that IP 6 is an essential co-factor for cleavage module maturation. [Display omitted] • BRAT1 and WDR73 are assembly factors for the RNA cleavage module of Integrator • They inhibit the endonuclease INTS11 by physically blocking its active site • Final maturation of the cleavage module is mediated by IP 6 in the nucleus • Several neurodevelopmental disorders are caused by cleavage module assembly defects Sabath et al. reveal that BRAT1 and WDR73 are crucial for forming Integrator's RNA cleavage module, stabilizing assembly intermediates, facilitating nuclear import, and preventing spurious activity. The final nuclear maturation step is mediated by IP 6. Mutations in both factors cause Integrator misassembly and malfunction, which leads to neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Objective(s): Dietary phytate is known to protect against azoxymethane (AOM)-induced preneoplastic lesions. The present study was designed to determine whether dietary phytate affects mutation frequency in colon epithelial cells challenged with azoxymethane in vivo, through lowering the formation of O6-methyl guanosine (O6-MeG) and 8-hydroxy deoxyguanosine (8-OHdG) adducts.Materials and Methods: We used Fisher F344 rats induced with AOM for 20 weeks and undertook 1% or 2% phytate supplementation for subsequent 16 weeks to monitor the mutation frequencies of one of the candidate genes, K-ras, along with DNA adduct load.Results: Dietary phytate significantly suppressed aberrant crypt foci formation and effectively inhibited colon tumor formation in a dose-dependent manner. DNA sequencing results demonstrated that 60% of the colon tumors from AOM-treated and control diet fed animals showed GGT to GAT transition and 40% of the tumors showed GGT to GTT transversion at codon 12, along with 18% of the tumors showing GGC to CGC transversion at codon 13. Phytate supplementation at 1 and 2% lowered the frequency of GGT > GAT to 30 and 10%, respectively. Phytate supplementation also nullified the codon 13 mutations. No mutations were observed at codon 61 in any of the experimental groups.Conclusion: The lowered frequency of K-ras mutations correlated with decreased formation of hydroxyl radicals, O5-meG and 8-OH-dG levels in phytate-supplemented animals with lowered tumor burden.

Objectives: The objective of this study was to identify the role of reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in inositol hexaphosphate (IP6)-induced metabolic disruption in human leukemia PLB-985 cells. Methods: PLB-985 and X chromosome linked gp91-phox gene knockout (X-CGD) cells were treated with 5, 10, or 20 mM IP6 for 24 to 72 h. Cell growth was assayed using a highly water-soluble tetrazolium salt. The rate of apoptotic and necrotic cell death was determined with an Annexin V-fluorescein isothiocyanate/propidium iodide kit. The expression of CD11b as a marker of monocytic property and of LC3 as an autophagy marker was tested, using flow cytometry combined with fluorescent antibodies. Results: Treatment with 5 and 10 mM IP6 for 24 h was found to suppress the growth of both cell lines, though the effect was more dramatic in PLB-985 cells. After 6-h treatment with 20 mM IP6, the necrosis rate of PLB-985 cells was significantly greater than that of X-CGD cells. Further, after 72-h treatment with 10 mM IP6, CD11b expression was observed in PLB-985 cells but inhibited in X-CGD cells. Autophagy monitoring after 6-h treatment with 10 mM IP6 revealed that LC3 expression was suppressed in PLB-985 cells, whereas it was somewhat increased in X-CGD cells. Conclusions: Our results suggest that NADPH oxidase activation mediates IP6-induced metabolic disruption associated with necrosis, differentiation, cell growth, and autophagy in PLB-985 cells.

Inositol hexaphosphate (IP6) is a dietary compound commonly obtained from corn, rice, etc. Although we may consume significant amount of IP6 daily, it is unclear whether this diet will impact macrophages' fate and function. Therefore, we characterized the underlying relationship between IP6 and macrophage polarization in this study. We specifically examined the signature gene expression profiles associated with pro‐ and anti‐inflammatory responses, and resolution of inflammation pathways in macrophages under the influence of IP6. Interestingly, our data suggested that IP6 polarizes bone marrow‐derived macrophages (BMDM) into an M2a‐like subtype. Our results also demonstrated that IP6 reduces lipopolysaccharide‐induced apoptosis and pro‐inflammatory responses in macrophages. In contrast, the expression levels of genes related to anti‐inflammatory responses and resolution of inflammation pathways are upregulated. Our findings collectively demonstrated that IP6 has profound modulation effects on macrophages, which warrant further research on the therapeutic benefits of IP6 for inflammatory diseases. [ABSTRACT FROM AUTHOR]

The formation of metal complexes with phytic acid is a complex process that depends strongly on the metal-to-ligand molar ratio, pH value and consequent protonation level of the phytate ligand as well as accompanying side reactions, in particular metal hydrolysis and precipitation of the formed coordination compounds. In the present work, the potentiometric titration technique was used in combination with a detailed analysis of the equivalent point dependencies for selected biologically relevant monovalent and divalent cations from the groups of alkaline earths and transition metals, namely: Mg(II), Zn(II), Fe(II), Cu(I), and Cu(II) ions. The investigation of complex formation mechanism, the evaluation of the species formed, and the identification of other side reactions was based on the examination of three distinct equivalent points, which were detectable by alkalimetric titrations of phytic acid in the presence of selected metal ions. It has been demonstrated that alkaline earth metals interact with different binding site(s) than the transition metals, and experiments with both oxidation states of copper revealed similar complexing characteristics, which depend mainly on the ionic radius (and not on the ionic charge as initially expected). Quantitative data on phytate complexation, hydroxide formation and complex precipitation are presented herein for all metals studied, including Cu(I), which was investigated for the first time by means of alkalimetric titration.

Background and Purpose: No therapy is approved for vascular calcification or calcific uraemic arteriolopathy (calciphylaxis), which increases mortality and morbidity in patients undergoing dialysis. Deposition of hydroxyapatite (HAP) crystals in arterial walls is the common pathophysiologic mechanism. The mechanism of action of SNF472 to reduce HAP deposition in arterial walls was investigated.Experimental Approach: We examined SNF472 binding features (affinity, release kinetics and antagonism type) for HAP crystals in vitro, inhibition of calcification in excised vascular smooth muscle cells from rats and bone parameters in osteoblasts from dogs and rats.Key Results: SNF472 bound to HAP with affinity (KD ) of 1-10 μM and saturated HAP at 7.6 μM. SNF472 binding was fast (80% within 5 min) and insurmountable. SNF472 inhibited HAP crystal formation from 3.8 μM, with complete inhibition at 30.4 μM. SNF472 chelated free calcium with an EC50 of 539 μM. Chelation of free calcium was imperceptible for SNF472 1-10 μM in physiological calcium concentrations. The lowest concentration tested in vascular smooth muscle cells, 1 μM inhibited calcification by 67%. SNF472 showed no deleterious effects on bone mineralization in dogs or in rat osteoblasts.Conclusion and Implications: These experiments show that SNF472 binds to HAP and inhibits further HAP crystallization. The EC50 for chelation of free calcium is 50-fold greater than a maximally effective SNF472 dose, supporting the selectivity of SNF472 for HAP. These findings indicate that SNF472 may have a future role in the treatment of vascular calcification and calcific uraemic arteriolopathy in patients undergoing dialysis. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer, one of the most common tumors, is mainly fatal because of the occurrence of liver metastasis. Inositol hexaphosphate (IP6) and inositol (INS) were found, both, in vitro and in vivo to play an anti-tumor effect, whereas the combination of IP6 and INS was more effective than IP6 or INS alone. Materials and Methods: The inhibitory effects of IP6, INS and the combination of IP6+INS on tumor progression and liver metastasis of colorectal cancer were investigated in an orthotopic transplantation model of colorectal cancer. The tumor-bearing mice were selected by in vivo bioluminescence imaging and were treated with IP6, INS, and IP6 combined with INS, respectively. All mice were sacrificed after 6 weeks of treatment. The cancer development and metastasis were compared among the groups. The expression of genes related to the Wnt/β-catenin in the model was analyzed. Results: The results demonstrated that liver metastasis was inhibited after treatment with IP6, INS, and IP6+INS. Compared to that of the M_G, survival period was extended, and tumor weight was lowered in IP6_G, INS_G, and IP6+INS_G. Besides, the liver metastatic area of mice in IP6+INS_G was relatively smaller than that in M_G, IP6_G, or INS_G. The results of RNA-seq analysis showed that the expressions of Wnt10b, Tcf7, and c-Myc were significantly downregulated in IP6+INS_G compared to that in M_G (P< 0.05). Results of real-time PCR and Western blot showed that mRNA and protein expressions of β-catenin, Wnt10b, Tcf7, and c-Myc were significantly lower in IP6+INS_G compared to that in M_G (P< 0.05). Discussion: IP6+INS was more effective in inhibiting liver metastasis of colorectal cancer than IP6 or INS alone. The better inhibition effect may be accomplished through regulating the mutation of Wnt/β-catenin signaling pathway by inhibiting Wnt10b, Tcf7, β-catenin, and c-Myc from abnormally high expression. [ABSTRACT FROM AUTHOR]

This study evaluated the inhibitory effect of phytic acid (PA) on the spore germination and vegetative cells growth of Clostridium perfringens type A, as well as its effect in combination with maltodextrin (MD) in cooked sausages. The addition of 1% PA showed a satisfactory inhibition of spores’ germination and vegetative cells growth of C. perfringens in BHI media. The inhibitory effect of 1% PA on vegetative cells was similar to the additive sodium sorbate (SS) at 10%. Subsequently, a mixture of PA-MD (1:1; w/w) was evaluated for the inhibition of C. perfringens spores in cooked sausages. The PA-MD 1.5% and 2.5% had a similar performance to SS 10% and a similar or higher performance than 0.015% NO2 (p < 0.05). In an unprecedented way, the present study demonstrated that PA inhibited spore germination and vegetative cells growth of C. perfringens, highlighting its potential use as an alternative and natural preservative for the meat industry.

Objective(s): Dietary phytate is known to protect against azoxymethane (AOM)-induced preneoplastic lesions. The present study was designed to determine whether dietary phytate affects mutation frequency in colon epithelial cells challenged with azoxymethane in vivo, through lowering the formation of O6-methyl guanosine (O6-MeG) and 8-hydroxy deoxyguanosine (8-OHdG) adducts. Materials and Methods: We used Fisher F344 rats induced with AOM for 20 weeks and undertook 1% or 2% phytate supplementation for subsequent 16 weeks to monitor the mutation frequencies of one of the candidate genes, K-ras, along with DNA adduct load. Results: Dietary phytate significantly suppressed aberrant crypt foci formation and effectively inhibited colon tumor formation in a dose-dependent manner. DNA sequencing results demonstrated that 60% of the colon tumors from AOM-treated and control diet fed animals showed GGT to GAT transition and 40% of the tumors showed GGT to GTT transversion at codon 12, along with 18% of the tumors showing GGC to CGC transversion at codon 13. Phytate supplementation at 1 and 2% lowered the frequency of GGT > GAT to 30 and 10%, respectively. Phytate supplementation also nullified the codon 13 mutations. No mutations were observed at codon 61 in any of the experimental groups. Conclusion: The lowered frequency of K-ras mutations correlated with decreased formation of hydroxyl radicals, O5-meG and 8-OH-dG levels in phytate-supplemented animals with lowered tumor burden. [ABSTRACT FROM AUTHOR]

Inositol hexaphosphate (IP6), a food constituent with various health benefits, has been shown to suppress postprandial elevations of serum uric acid (SUA) levels in healthy adults by inhibiting purine nucleoside and base absorption. Here, we investigated the effect of repeated intake of IP6 on fasting SUA levels in hyperuricemic subjects. This randomized double-blind placebo-controlled crossover design study included 31 asymptomatic hyperuricemic subjects (fasting SUA level > 7.0 but <9.0 mg/dL). Subjects ingested placebo or IP6 drinks (600 mg twice daily) during two 2-week intervention periods with a 2-week washout period. The primary outcome was fasting SUA level; the secondary outcome was the urinary uric acid to creatinine ratio. Fasting SUA levels in the IP6 group were lower than those in the placebo group (p < 0.05). The urinary uric acid to creatinine ratio did not change between the placebo and IP6 groups (p > 0.05). This study showed that a 2-weeks supplementation period of 600 mg IP6 twice daily can improve fasting SUA levels in hyperuricemic subjects. [ABSTRACT FROM AUTHOR]

Phosphorous (P) cycling is often closely coupled to iron (Fe), particularly following mineral weathering or in hydromorphic soils where Fe redox reactions can control the equilibrium between P retention and release. While surface adsorption of P on Fe (hydr)oxides is a well-known and widely studied process, less attention has been devoted to the understanding of P (especially organic P) coprecipitation following Fe(II) oxidative precipitation. In this work we synthesized and followed the kinetics of a series of Fe-P systems with increasing P/Fe ratio, prepared by either surface adsorption on ferrihydrite (Fh) or oxidative coprecipitation of Fe(II) with inorganic phosphate (Pi), inositol hexaphosphate (myo InsP6) or phosphatidylcholine (PC). The obtained materials were characterized for P and Fe contents, specific surface area (SSA), porosity and surface charge. XRD, TEM, XPS and IR techniques were used to investigate their properties. P retention by coprecipitation was generally greater with respect to adsorption, especially at the highest initial P/Fe ratio. Inorganic phosphate caused interference and poisoning of the crystallization process, slowing down Fe(II) oxidation and precipitation rates at low P/Fe ratios, with the formation of nanometric particles and phosphate concentrated on their surface. With increasing P loadings, more aggregated particles with a lower SSA and greater porosity were obtained. Aside from precipitation, the retention mechanisms also involved adsorption and/or inclusion of Pi within the particles. myo InsP6, on the other hand, contributed to accelerating the precipitation of Fe, leading to coprecipitates bearing the organic P compound within the structure, and was retained by precipitation and adsorption mechanisms. Conversely, irrespective of the P/Fe ratio, PC did not influence the rate of Fe(II) oxidation and precipitation due to its hydrophobic character. The prevailing mechanism involved in its retention during coprecipitation was physical retention on the surface, leading to a drastic decrease of SSA and pore volume. Coprecipitation is thus a complex process, involving several mechanisms as a function of the P species and initial P/Fe ratio, and further contributing to the stabilization and selective accumulation of myo InsP6 in soil with respect to other organic P forms. • Coprecipitation of inorganic P (Pi) and organic P (myo InsP6 and PC) during Fe(II) oxidation was evaluated. • Coprecipitation offers a much higher organic P retention than adsorption. • Fe(II) oxidative precipitation kinetics were strongly affected by Pi and myo InsP6, but not by PC. • Coprecipitation of Pi and myo InsP6 strongly influenced surface properties as a function of initial P/Fe ratio. • Coprecipitation is a complex process playing a pivotal role in the fate of organic P compounds in soil. [ABSTRACT FROM AUTHOR]

Today’s fertilizers rely heavily on mining phosphorus (P) rocks. These rocks are known to become exhausted in near future, and therefore effective P use is crucial to avoid food shortage. A substantial amount of P from fertilizers gets adsorbed onto soil minerals to become unavailable to plants. Understanding P interaction with these minerals would help efforts that improve P efficiency. To this end, we performed a molecular level analysis of the interaction of common organic P compounds (glycerolphosphate (GP) and inositol hexaphosphate (IHP)) with the abundant soil mineral (goethite) in presence of water. Molecular dynamics simulations are performed for goethite–IHP/GP–water complexes using the multiscale quantum mechanics/molecular mechanics method. Results show that GP forms monodentate (M) and bidentate mononuclear (B) motifs with B being more stable than M. IHP interacts through multiple phosphate groups with the 3M motif being most stable. The order of goethite–IHP/GP interaction energies is GP M < GP B < IHP M < IHP 3M. Water is important in these interactions as multiple proton transfers occur and hydrogen bonds are formed between goethite–IHP/GP complexes and water. We also present theoretically calculated infrared spectra which match reasonably well with frequencies reported in literature.

From the early precipitation-based techniques, introduced more than a century ago, to the latest development of enzymatic bio- and nano-sensor applications, the analysis of phytic acid and/or other inositol phosphates has never been a straightforward analytical task. Due to the biomedical importance, such as antinutritional, antioxidant and anticancer effects, several types of methodologies were investigated over the years to develop a reliable determination of these intriguing analytes in many types of biological samples; from various foodstuffs to living cell organisms. The main aim of the present work was to critically overview the development of the most relevant analytical principles, separation and detection methods that have been applied in order to overcome the difficulties with specific chemical properties of inositol phosphates, their interferences, absence of characteristic signal (e.g., absorbance), and strong binding interactions with (multivalent) metals and other biological molecules present in the sample matrix. A systematical and chronological review of the applied methodology and the detection system is given, ranging from the very beginnings of the classical gravimetric and titrimetric analysis, through the potentiometric titrations, chromatographic and electrophoretic separation techniques, to the use of spectroscopic methods and of the recently reported fluorescence and voltammetric bio- and nano-sensors.

Graphical abstract Highlights • L-Cys/IP 6 @Ag is prepared as SERS substrate by a simple method. • Accumulations Cu2+ by IP 6 and L-Cys elevates detection sensitivity. • pH control and L-Cys oxidation with Cu2+ improves SERS selectivity. • L-Cys/IP 6 @Ag –based SERS assay detects trace Cu2+ in river water. Abstract Developing detection method for trace copper ions (Cu2+) has attracted great attention since Cu2+ ions would threaten to human health, including cellular toxicity, liver damage, and neuro degenerative diseases. In this work, adding L-cysteine (L-Cys) into inositol hexaphosphate (IP 6) modified Ag nanoparticles (designated as L-Cys/IP 6 @Ag) induces the certain aggregation of nanoparticles, resulting in increasng the surface enhanced Raman scattering (SERS) signal of rhodamine 6 G (R6 G). The presence of Cu2+ ions could be adsorbed by IP 6 and the concentrated Cu2+ ions could further selectively oxide Cys molecules under certain pH value, which disperses the IP 6 @Ag again and decreases the SERS signal of R6 G. The linear range of determination of Cu2+ ions is from 10−5 to 10-1° M as well as a low detection concentration is of 10 pM. Furthermore, the L-Cys/IP 6 @Ag-R6 G-based SERS sensor has been successfully applied to detect trace Cu2+ in river water. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the zootechnical performance of Nile tilapia (Oreochromis niloticus) fed with plant ingredients, supplemented with granulated and liquid phytase enzyme. To carry out the study was used 600 Nile tilapia juveniles (mean initial weight of 1.72 ± 2.21 g and mean initial length of 9.46 ± 0.64 cm) sexually inverted into males, during 64 days. The experimental design was completely randomized with six diets: negative control (without inorganic phosphate and without addition of phytase), positive control (with inorganic phosphate), Two diets (1500 and 3000 FTU/kg) with phytase in the granulated and two diets (1500 and 3000 FTU/kg) with phytase in liquid, in with five replicates. The diets were isoenergetic with 3100 kcal/kg and isoproteic with 28% crude protein. The granulated phytase was added before and after extrusion and the liquid phytase added after processing. Phytase liquid form provided best performance and the best protein content in the carcass. The same also was observed for the coefficients of apparent digestibility of protein and mineral matter. Retention of phosphorus in the plasma and vertebrae was not influenced by the treatments. With the results it is concluded that the addition of phytase in the liquid form is more efficient, and the diets can be added at lower levels. [ABSTRACT FROM AUTHOR]

Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is suspected that lithium's inhibition of GSK3 causes rhythm changes, it is not known if inositol polyphosphates can also affect the circadian clock. We examined whether the signaling molecule inositol hexaphosphate (IP 6 ) has effects on circadian rhythms. Using a bioluminescent reporter (Per2::luc) to measure circadian rhythms, we determined that IP 6 increased rhythm amplitude and shortened period in NIH3T3 cells. The IP 6 effect on amplitude was attenuated by selective siRNA knockdown of GSK3B and pharmacological blockade of AKT kinase. However, unlike lithium, IP 6 did not induce serine-9 phosphorylation of GSK3B. The synthesis of IP 6 involves the enzymes inositol polyphosphate multikinase (IPMK) and inositol pentakisphosphate 2-kinase (IPPK). Knockdown of Ippk had effects opposite to those of IP 6 , decreasing rhythm amplitude and lengthening period. Ipmk knockdown had few effects on rhythm alone, but attenuated the effects of lithium on rhythms. However, lithium did not change the intracellular content of IP 6 in NIH3T3 cells or neurons. Pharmacological inhibition of the IP 6 kinases (IP6K) increased rhythm amplitude and shortened period, suggesting secondary effects of inositol pyrophosphates may underlie the period shortening effect, but not the amplitude increasing effect of IP 6 . Overall, we conclude that inositol phosphates, in particular IP 6 have effects on circadian rhythms. Manipulations affecting IP 6 and related inositol phosphates may offer a novel means through which circadian rhythms can be regulated. [ABSTRACT FROM AUTHOR]

[Display omitted] • We identified a correlation between CLDN23 expression and the occurrence of liver metastases in colorectal cancer patients. • The combination of IP6 and INS inhibited proliferation, invasion, and migration ability after the treatment with IP6 and INS. • The combination of IP6 and INS upregulated occludin and ZO-1, while downregulated CLDN23, RhoA, ROCK-1, and p-MLC2. Colorectal cancer is a prevalent malignant tumor, with liver metastases being the primary cause of death. The combination of inositol hexaphosphate (IP6) and inositol (INS) has been shown to inhibit colorectal cancer metastasis. We identified a correlation between CLDN23 expression and the occurrence of liver metastases in colorectal cancer patients. Following the transfection with the lentiviral vector (LV-CLDN23-RNAi), proteomic analysis of SW620 revealed significant alterations in the occludin, ZO-1, RhoA, and ROCK-1 genes expression by western blotting. We found that both SW620 and SW480 cells showed inhibited proliferation, invasion, and migration ability after the treatment with IP6 and INS. Additionally, this combination upregulated occludin and ZO-1, while downregulated CLDN23, RhoA, ROCK-1, and p-MLC2. In conclusion, the combination of IP6 and INS suppressed the proliferation, invasion, and migration of colorectal cancer cells and regulated CLDN23 expression by enhancing tight junction proteins, such as occludin and ZO1, via the RhoA /ROCK1 pathway. [ABSTRACT FROM AUTHOR]

Maternal exposure to a carcinogen is associated with increased risk of different cancers in the offspring. The foetus is highly sensitive to carcinogens and this contributes to the foetal basis of the onset of disease. The better understanding of the molecular mechanisms involved in the early stage of lung tumourigenesis in the offspring is needed for the newer preventive strategies. We evaluated the effects of N-ethyl-N-nitrosourea (ENU) given on the 17th day of gestation and antitumour agent inositol hexaphosphate (IP6) to the mothers at the early stage of lung tumourigenesis in F1 mice. There was no treatment related effects on the litter size or body weight of the F1 mice at the PND12 or 24. Analysis of PCNA, NF-κB (p50), IL-6, COX-2, pSTAT3, STAT3, caspase-3, caspase-9, PARP, Akt signalling and downstream cyclin D1 along with miR-155, suggested the modulation of proliferation, inflammation and apoptosis at PND12 and 24. IP6 administration to the predisposed mothers prevented the proliferation, inflammation and enhanced apoptosis in F1 lung as showed by a reduction in PCNA, NF-κB (p50), IL-6, COX-2, pSTAT3, STAT3, miR-155 and increase in caspases, cleavage of poly (ADP-ribose) polymerase. IP6 administration also inhibited the activation of Akt and cyclin D1. Our study shows that tumourigenic changes take place in the lungs of the F1 generation from the carcinogen predisposed mothers even before the onset of tumours and the simultaneous intake of chemopreventive agent during the gestation or lactation period could prevent the lymphocytic infiltration and hyperplasia preceding the tumourigenesis.

OBJECTIVE: Oral treatment with inositol hexaphosphate (InsP6) has shown to be efficient in decreasing adverse effects in patients with breast cancer under chemotherapy. This study was aimed at evaluating and comparing the efficacy of topical InsP6 in improving quality of life in women treated with anticancer drugs. PATIENTS AND METHODS: The study was a double-blind, randomized controlled trial (RCT) with allocation concealment of 20 patients in two groups, one (experimental) applied 4% topical formulation of InsP6 once a day, whereas the second one (control) a gel containing hyaluronic acid. InsP6 therapy started 6 weeks after lumpectomy. Blood tests were monitored in both groups and quality of life was assessed using standardized QLQ-C30 and QLQ-BR23. RESULTS: Patients who applied InsP6 on the breast significantly improved their quality of life and functional status reducing side effects compared to control group; moreover, after treatment, a significant difference between the two groups was observed in the white blood cells and platelets count values. CONCLUSIONS: Topical InsP6 treatment has demonstrated to be effective and safe in preventing and/or mitigating chemotherapy-induced side effects as well as the preserving quality of life in women with ductal breast cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of inositol hexaphosphate (IP6) on proliferation of human osteosarcoma cell line MG-63 and primary cultured osteoblasts so as to explore the optimal concentration for achieving anti-cancer effects. Methods We primary cultured and identified human osteoblasts. Then we made recovery and normal culture of human osteosarcoma cell line MG-63. We tested the proliferation of two kinds of cell lines under different concentrations of IP6 by MTT to determine the optimal concentration and then detected MG-63 cell cycle and apoptosis by flow cytometry. Results When IP6 concentration was more than 1mmol/L, IP6 began to inhibit the proliferation of MG-63 cell line in the time-dose dependent manner. When the concentration reached 4mmol/L, this inhibitory effect was the maximum. When IP6 concentration was 0.5mmol/L or 1mmol/L, the proliferation of osteoblasts was not obviously inhibited. When it was 2 mmol/L, the proliferation was slightly inhibited. A concentration of 4mmol/L caused the apoptosis of osteoblasts. Conclusion IP6 can inhibit the proliferation of osteosarcoma cell line MG-63 and lead to its apoptosis. The optimal concentration is 2mmol/L for achieving anti-cancer effects. [ABSTRACT FROM AUTHOR]

Metal ions or metal (hydrogen) oxides are widely used as active sites in the construction of phosphate-adsorbing materials in water, but the removal of soluble organophosphorus from water remains technically difficult. Herein, synchronous organophosphorus oxidation and adsorption removal were achieved using electrochemically coupled metal–hydroxide nanomaterials. La–Ca/Fe–layered double hydroxide (LDH) composites prepared using the impregnation method removed both phytic acid (inositol hexaphosphate, IHP) and hydroxy ethylidene diphosphonic acid (HEDP) acid under an applied electric field. The solution properties and electrical parameters were optimized under the following conditions: organophosphorus solution pH = 7.0, organophosphorus concentration = 100 mg L−1, material dosage = 0.1 g, voltage = 15 V, and plate spacing = 0.3 cm. The electrochemically coupled LDH accelerates the removal of organophosphorus. The IHP and HEDP removal rates were 74.9% and 47%, respectively in only 20 min, 50% and 30% higher, respectively, than that of La–Ca/Fe–LDH alone. The removal rate in actual wastewater reached 98% in only 5 min. Meanwhile, the good magnetic properties of electrochemically coupled LDH allow easy separation. The LDH adsorbent was characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analysis. It exhibits a stable structure under electric field conditions, and its adsorption mechanism mainly includes ion exchange, electrostatic attraction, and ligand exchange. This new approach for enhancing the adsorption capacity of LDH has broad application prospects in organophosphorus removal from water. [Display omitted] • Electrochemistry promoted the removal of organophosphorus oxidation. • The electrochemical performance of LDH for removal of organophosphorus was enhanced. • Electrochemistry can save phosphorus removal time in practical application. [ABSTRACT FROM AUTHOR]

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.