Photodynamic Therapy with Targeted Release of Boron-Dipyrromethene Dye from Cobalt(III) Prodrugs in Red Light.

Boron-dipyrromethene (BODIPY) dyes are promising photosensitizers for cellular imaging and photodynamic therapy (PDT) owing to their excellent photophysical properties and the synthetically tunable core. Metalation provides a convenient way to overcome the drawbacks arising from their low aqueous solubility. New photo-/redox-responsive Co(III) prodrug chaperones are developed as anticancer PDT agents for efficient cellular delivery of red-light-active BODIPY dyes. The photobiological activity of heteroleptic Co(III) complexes derived from tris(2-pyridylmethyl)amine (TPA) and acetylacetone-conjugated PEGylated distyryl BODIPY (HL1) or its dibromo analogue (HL2), [CoIII(TPA)(L1/L2)](ClO4)2 (1 and 2), are investigated. The Co(III)/Co(II) redox potential is tuned using the Co(III)-TPA scaffold. Complex 1 displays the in vitro release of BODIPY on red light irradiation. Complex 2, having good singlet oxygen quantum yield (ΦΔ âˆ¼ 0.28 in DMSO), demonstrates submicromolar photocytotoxicity to HeLa cancer cells (IC50 ≈ 0.23 µM) while being less toxic to HPL1D normal cells in red light. Cellular imaging using the emissive complex 1 shows mitochondrial localization and significant penetration into the HeLa tumor spheroids. Complex 2 shows supercoiled DNA photocleavage activity and apoptotic cell death through phototriggered generation of reactive oxygen species. The Co(III)-BODIPY prodrug conjugates exemplify new type of phototherapeutic agents with better efficacy than the organic dyes alone in the phototherapeutic window.

Bioactivity of human dental pulp-derived stem cells with boron-controlled S-PRG filler eluate by anion exchange.

Surface pre-reacted glass-ionomer (S-PRG) filler is a bioactive glass filler capable of releasing various ions. A culture medium to which was added an S-PRG filler eluate rich in boron was reported to enhance alkaline phosphatase (ALP) activity in human dental pulp-derived stem cells (hDPSC). To clarify the role of boron eluted from S-PRG fillers, the modified S-PRG filler eluate with different boron concentrations was prepared by using an anion exchange material. Therefore, elemental mapping analysis of anion exchange material, adsorption ratio, hDPSCs proliferation and ALP activity were evaluated. For statistical analysis, Kruskal-Wallis test was used, with statistical significance determined at p<0.05. ALP activity enhancement was not observed in hDPSC cultured in the medium that contained the S-PRG filler eluate from which boron had been removed. The result suggested the possibility that an S-PRG filler eluate with controlled boron release could be useful for the development of novel dental materials.

Effect of salinity stress and surfactant treatment with zinc and boron on morpho-physiological and biochemical indices of fenugreek (Trigonella foenum-graecum).

Micronutrient application has a crucial role in mitigating salinity stress in crop plants. This study was carried out to investigate the effect of zinc (Zn) and boron (B) as foliar applications on fenugreek growth and physiology under salt stress (0 and 120 mM). After 35 days of salt treatments, three levels of zinc (0, 50, and 100 ppm) and two levels of boron (0 and 2 ppm) were applied as a foliar application. Salinity significantly reduced root length (72.7%) and shoot length (33.9%), plant height (36%), leaf area (37%), root fresh weight (48%) and shoot fresh weight (75%), root dry weight (80%) and shoot dry weight (67%), photosynthetic pigments (78%), number of branches (50%), and seeds per pod (56%). Fenugreek's growth and physiology were improved by foliar spray of zinc and boron, which increased the length of the shoot (6%) and root length (2%), fresh root weight (18%), and dry root weight (8%), and chlorophyll a (1%), chlorophyll b (25%), total soluble protein content (3%), shoot calcium (9%) and potassium (5%) contents by significantly decreasing sodium ion (11%) content. Moreover, 100 ppm of Zn and 2 ppm of B enhanced the growth and physiology of fenugreek by reducing the effect of salt stress. Overall, boron and zinc foliar spray is suggested for improvement in fenugreek growth under salinity stress.

PI3K/Akt signaling pathway mediates the effect of low-dose boron on barrier function, proliferation and apoptosis in rat intestinal epithelial cells.

Boron is an essential trace element with roles in growth, development, and physiological functions; however, its mechanism of action is still unclear. In this study, the regulatory roles of the PI3K/Akt signaling pathway on boron-induced changes in barrier function, proliferation, and apoptosis in rat intestinal epithelial cells were evaluated. Occludin levels, the proportion of cells in the G2/M phase, cell proliferation rate, and mRNA and protein expression levels of PCNA were higher, while the proportions of cells in the G0/G1 and S phases, apoptosis rate, and caspase-3 mRNA and protein expression levels were lower in cells treated with 0.8 mmol/L boron than in control IEC-6 cells (P < 0.01 or P < 0.05). However, 40 mmol/L boron decreased ZO-1 and Occludin levels, the proportion of cells in the G2/M phase, cell proliferation rate, and mRNA and protein levels of PCNA and increased the apoptosis rate and caspase-3 mRNA expression (P < 0.01 or P < 0.05). After specifically blocking PI3K and Akt signals (using LY294002 and MK-2206 2HCL), 0.8 mmol/L boron had no effects on Occludin, PCNA level, apoptosis rates, and caspase-3 levels (P < 0.05); however, the proliferation rate and PCNA levels decreased significantly (P < 0.01 or P < 0.05). The addition of 40 mmol/L boron did not affect ZO-1 and Occludin levels and did not affect the apoptosis rate or PCNA and caspase-3 levels. These results suggested that the PI3K/Akt signaling pathway mediates the effects of low-dose boron on IEC-6 cells.

Effects of Boron on Fat Synthesis in Porcine Mammary Epithelial Cells.

This study aimed to investigate the effect of boron on porcine mammary epithelial cells (PMECs) survival, cell cycle, and milk fat synthesis. PMECs from boron-treated groups were exposed to 0-80 mmol/L boric acid concentrations. Cell counting kit-8 and flow cytometry assays were performed to assess cell survival and the cell cycle, respectively. Triacylglycerol (TAG) levels in PMECs and culture medium were determined by a triacylglycerol kit while PMECs lipid droplet aggregation was investigated via oil red staining. Milk fat synthesis-associated mRNA levels were determined by quantitative real-time polymerase chain reaction (qPCR) while its protein expressions were determined by Western blot. Low (0.2, 0.3, 0.4 mmol/L) and high (> 10 mmol/L) boron concentrations significantly promoted and inhibited cell viabilities, respectively. Boron (0.3 mmol/L) markedly elevated the abundance of G2/M phase cells. Ten mmol/L boron significantly increased the abundances of G0/G1 and S phase cells, but markedly suppressed G2/M phase cell abundance. At 0.3 mmol/L, boron significantly enhanced ERK phosphorylation while at 0.4, 0.8, 1, and 10 mmol/L, it markedly decreased lipid droplet diameters. Boron (10 mmol/L) significantly suppressed ACACA and SREBP1 protein expressions. The FASN protein levels were markedly suppressed by 0.4, 0.8, 1, and 10 mmol/L boron. Both 1 and 10 mmol/L markedly decreased FASN and SREBP1 mRNA expressions. Ten mmol/L boron significantly decreased PPARα mRNA levels. Low concentrations of boron promoted cell viability, while high concentrations inhibited PMECS viabilities and reduced lipid droplet diameters, which shows the implications of boron in pregnancy and lactation.

Sodium Pentaborate Prevents Acetaminophen-Induced Hepatorenal Injury by Suppressing Oxidative Stress, Lipid Peroxidation, Apoptosis, and Inflammatory Cytokines in Rats.

Acetaminophen (N-acetyl-p-aminophenol, APAP, or paracetamol) is one of the drugs that may be damaging to the kidneys and liver when used in excess. In this context, it is vital to treat these side effects on the liver and kidneys with various antioxidants. Diseases have been treated using herbal and mineral remedies since ancient times. The mineral boron, found in rocks and water, is a crucial ingredient with multiple positive biological effects. The primary objective of this research is to determine whether or not boron has a protective effect against the toxicity generated by APAP in rats. Male Sprague-Dawley rats were pretreated orally with boron-source sodium pentaborate (B50 and B100 mg/kg) for 6 days by gastric gavage in order to counteract the toxicity caused by a single dose of APAP (1g/kg). APAP increased lipid peroxidation as well as serum BUN, creatinine concentrations, and serum activities of AST, ALP, and ALT by consuming GSH in liver and kidney tissues. In addition, the activity of antioxidative enzymes, including SOD, CAT, and GPx, was diminished. Inflammatory indicators such as TNF-α, IL-1ß, and IL-33 were elevated in conjunction with APAP toxicity. In kidney and liver tissues, APAP dramatically increased the activity of caspase-3 and triggered apoptosis. Sodium pentaborate therapy on a short-term basis reduced biochemical levels despite these effects of APAP. This study showed that boron protects rats from the harmful effects of APAP by acting as an anti-inflammatory, antioxidant, and anti-apoptotic agent.

Boron-containing carbonic anhydrases inhibitors.

Over the last decades, the medicinal chemistry of boron-based compounds has been extensively explored, designing valuable small molecule drugs to tackle diseases and conditions, such as cancer, infections, inflammatory and neurological disorders. Notably, boron has proven to also be a valuable element for the development of inhibitors of the metalloenzymes carbonic anhydrases (CAs), a class of drug targets with significant potential in medicinal chemistry. Incorporating boron into carbonic anhydrase inhibitors (CAIs) can modulate the ligand ability to recognize the target and/or influence selectivity towards different CA isoforms, using the tail approach and boron-based tails. The electron-deficient nature of boron and its associated properties have also led to the discovery of novel zinc-binding CAIs, such as boronic acids and the benzoxaboroles, capable of inhibiting the CAs upon a Lewis acid-base mechanism of action. The present manuscript reviews the state-of-the-art of boron-based CAIs. As research in the applications of boron compounds in medicinal chemistry continues, it is anticipated that new boron-based CAIs will soon expand the current array of such compounds. However, further research is imperative to fully unlock the potential of boron-based CAIs and to advance them towards clinical applications.

Boron-containing coating yields enhanced antimicrobial and mechanical effects on translucent zirconia.

OBJECTIVES: To evaluate the mechanical and antimicrobial properties of boron-containing coating on translucent zirconia (5Y-PSZ). METHODS: 5Y-PSZ discs (Control) were coated with a glaze (Glaze), silver- (AgCoat), or boron-containing (BCoat) glasses. The coatings' antimicrobial potential was characterized using S. mutans biofilms after 48 h via viable colony-forming units (CFU), metabolic activity (CV) assays, and quantification of extracellular polysaccharide matrix (EPS). Biofilm architectures were imaged under scanning electron and confocal laser scanning microscopies (SEM and CLSM). The cytocompatibility was determined at 24 h via WST-1 and LIVE&DEAD assays using periodontal ligament stem cells (PDLSCs). The coatings' effects on properties were characterized by Vickers hardness, biaxial bending tests, and fractography analysis. Statistical analyses were performed via one-way ANOVA, Tukey's tests, Weibull analysis, and Pearson's correlation analysis. RESULTS: BCoat significantly decreased biofilm formation, having the lowest CFU and metabolic activity compared with the other groups. BCoat and AgCoat presented the lowest EPS, followed by Glaze and Control. SEM and CLSM images revealed that the biofilms on BCoat were thin and sparse, with lower biovolume. In contrast, the other groups yielded robust biofilms with higher biovolume. The cytocompatibility was similar in all groups. BCoat, AgCoat, and Glaze also presented similar hardness and were significantly lower than Control. BCoat had the highest flexural strength, characteristic strength and Weibull parameters (σF: 625 MPa; σ0: 620 MPa; m = 11.5), followed by AgCoat (σF: 464 MPa; σ0: 478 MPa; m = 5.3). SIGNIFICANCE: BCoat is a cytocompatible coating with promising antimicrobial properties that can improve the mechanical properties and reliability of 5Y-PSZ.

Antibacterial Activity of Boron Compounds Against Biofilm-Forming Pathogens.

This study aimed to evaluate the antibacterial activity of nine boron derivatives against biofilm-forming pathogenic bacteria. The effect of boron derivatives (CMB, calcium metaborate; SMTB, sodium metaborate tetrahydrate; ZB, zinc borate; STFB, sodium tetra fluorine borate; STB, sodium tetraborate; PTFB, potassium tetra fluor borate; APTB, ammonium pentabo-rate tetrahydrate; SPM, sodium perborate monohydrate; Borax, ATFB, ammonium tetra fluorine borate) on bacteria isolated from blood culture was determined by the minimum inhibitory concentration (MIC) method. Then, biofilm formation potentials on microplates, tubes, and Congo red agar were examined. The cytotoxicity of boron derivatives was determined by using WST-1-based methods. The interaction between the biofilm-forming bacteria, fibroblast cells, and boron derivatives was determined with the infection model. We found that the sodium metaborate tetrahydrate molecule was effective against all pathogens. According to the optical density values detected at 630 nm in microplates, meticillin-resistant Staphylococcus aureus was observed to have the most substantial biofilm ability at 0.257 nm. As a result of cytotoxicity studies, it has been determined that a 1 µg/L concentration of boron derivatives is not toxic to fibroblast L929 cells. In cell culture experiments, these boron derivatives have very serious inhibitory activity against biofilm-forming pathogens in a short treatment period, such as 2-4 h. Furthermore, using these molecules on inanimate surfaces affected by biofilms would be appropriate instead of living cells.

Investigation of cytotoxic antiproliferative and antiapoptotic effects of nanosized boron phosphate filled sodium alginate composite on glioblastoma cancer cells.

BACKGROUND: The effects of nanosized boron phosphate-filled sodium alginate composite gel (SA/BP) on the biological characteristics of three types of glioblastoma multiforme (GBM) cells (C6, U87MG and T98G) were examined in this study. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to determine the cytotoxicity of the composite gel on GBM, which was then compared to L929 healthy cells. Furthermore, wound healing, apoptosis, and colony formation capacities were evaluated. The investigation revealed that the SA/BP composite gel was successful in all GBM cells and could be used as a treatment agent for GBM and/or other invasive cancer types. METHODS AND RESULTS: According to the results, the SA/BP composite gel had no effect on healthy fibroblast cells but had a lethal effect on all glioblastoma cells. Additionally, the wound healing method was used to examine the effect of the SA/BP composite gel on cell migration. It was discovered that the wound closed in 24 h in untreated control group cells, while the SA/BP composite gel closed up to 29.62%, 26.77% and 11.31% of the wound for C6, U87MG and T98G cell lines respectively. SA/BP significantly reduced cell migration in cancer cells. The effect of the generated SA/BP composite gel on cell colony development was assessed using a colony formation assay, and the cells reduced colony formation for all GBMs. It was roughly 45% for 24 h and 30% for 48 h when compared to the control group for C6 cells, 33%(24 h) and 40%(48 h) for U87MG cells, 40%(24 h) and 43%(48 h) for T98G cells. DAPI(4',6-Diamidino-2-phenylindole) and JC-1(5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine, iodide) staining to evaluate apoptosis revealed that the SA/BP composite gel dramatically enhanced the frequency of all GBMs undergoing apoptosis. CONCLUSIONS: In line with experimental findings, it was observed that the SA/BP composite gel system did not affect healthy fibroblast cells but had a cytotoxic effect on glioblastoma cells, significantly reduced cell migration and colony-forming capacity of cells, and significantly increased apoptosis and depolarization of cell membranes. Based on all these findings, it can be said that SA/BP composite gel has cytotoxic, antiproliferative and antiapoptotic effects on different glioblastoma cells.

Chaotropic Effect-Induced Self-Assembly of the Malachite Green and Boron Cluster for Toxicity Regulation and Photothermal Therapy.

Malachite green (MG), a toxic antibacterial agent, is widely used in the farming industry. Effectively regulating the biotoxicity of this highly water-soluble cationic dye is challenging. Here, we present a novel strategy to reduce the biotoxicity of MG through the self-assembly of MG and the closo-dodecaborate cluster ([B12H12]2-) driven by the chaotropic effect. [B12H12]2- and MG in an aqueous solution can rapidly form an insoluble cubic-type supramolecular complex (B12-MG), and the original toxicity of MG is completely suppressed. Surprisingly, this supramolecular complex, B12-MG, has a strong UV-vis absorption peak at 600-800 nm and significant photothermal conversion efficiency under 660 nm laser irradiation. On this basis, B12-MG, the supramolecular complex, can be used as an efficient photothermal agent for antimicrobial photothermal therapy (PTT) both in vitro and in vivo. As a molecular chaperone of MG, [B12H12]2- not only can be applied as an antidote to regulate the biotoxicity of MG but also provides a novel method for the construction of photothermal agents for PTT based on the chaotropic effect.

In vivo investigation of boron-rich nanodrugs for treating triple-negative breast cancers via boron neutron capture therapy.

Triple-negative breast cancer (TNBC) is characterized by highly proliferative cancer cells and is the only subtype of breast cancer that lacks a targeted therapy. Boron neutron capture therapy (BNCT) is an approach that combines chemotherapy with radiotherapy and can potentially offer beneficial targeted treatment for TNBC patients owing to its unique ability to eradicate cancer cells selectively while minimizing damage to the surrounding healthy cells. Since BNCT relies on specific delivery of a high loading of B10 to the tumor site, there is growing research interest to develop more potent boron-based drugs for BNCT that can overcome the limitations of small-molecule boron compounds. In this study, polyethylene-glycol-coated boron carbon oxynitride nanoparticles (PEG@BCNO) of size 134.2±23.6nm were prepared as a promising drug for BNCT owing to their high boron content and enhanced biocompatibility. The therapeutic efficiency of PEG@BCNO was compared with a state-of-the-art 10BPA boron drug in mice bearing MDA-MB-231 tumor. In the orthotopic mouse model, PEG@BCNO showed higher B10 accumulation in the tumor tissues (6 µg 10B/g tissue compared to 3 µg 10B/g tissue in mice administered B10-enriched 10BPA drug) despite using the naturally occurring 11B/10B boron precursor in the preparation of the BCNO nanoparticles. The in vivo biodistribution of PEG@BCNO in mice bearing MDA-MB-231 showed a tumor/blood ratio of ~3.5, which is comparable to that of the state-of-the-art 10BPA-fructose drug. We further demonstrated that upon neutron irradiation, the mice bearing MDA-MB-231 tumor cells treated with PEG@BCNO and 10BPA showed tumor growth delay times of 9 days and 1 day, respectively, compared to mice in the control group after BNCT. The doubling times (DTs) for mice treated with PEG@BCNO and 10BPA as well as mice in the control group were calculated to be 31.5, 19.8, and 17.7 days, respectively. Immunohistochemical staining for the p53 and caspase-3 antibodies revealed that mice treated with PEG@BCNO showed lower probability of cancer recurrence and greater level of cellular apoptosis than mice treated with 10BPA and mice in the control group. Our study thus demonstrates the potential of pegylated BCNO nanoparticles in effectively inhibiting the growth of TNBC tumors compared to the state-of-the-art boron drug 10BPA.

Biotin and boron-dipyrromethene-tagged platinum(IV) prodrug for cellular imaging and mito-targeted photocytotoxicity in red light.

A platinum(IV) prodrug, cis,cis,trans-[Pt(NH3)2Cl2(biotin)(L)] (1), derived from cisplatin, where HL is the PEGylated red-light active boron-dipyrromethene (BODIPY) ligand, was synthesized, characterized and its photocytotoxicity evaluated. The complex showed a near-IR absorption band at 653 nm (ε ∼9.19 × 104 M-1 cm-1) in dimethyl sulfoxide and Dulbecco's phosphate-buffered saline (1 : 1 v/v) at pH 7.2. When excited at 630 nm, it showed an emission band at 677 nm in DMSO with a fluorescence quantum yield of 0.13. The 1,3-diphenylisobenzofuran titration experiment gave a singlet oxygen quantum yield (ΦΔ) of ∼0.32. A mechanistic DNA photocleavage study revealed singlet oxygen as the reactive oxygen species (ROS). The complex with biotin and PEGylated-distyryl-BODIPY showed significantly higher cellular uptake in A549 cancer cells as compared to non-cancerous Beas-2B cells from flow cytometry, indicating selectivity towards cancer cells. A dichlorodihydrofluorescein diacetate assay showed cellular ROS generation. Confocal images revealed predominant internalization in the mitochondria. The prodrug showed remarkable photodynamic therapy (PDT) activity in cancerous A549 and multidrug-resistant MDA-MB-231 cells with a high photocytotoxicity index value (half-maximal inhibitory concentration (IC50): 0.61-1.54 µM in red light), while being non-toxic in the dark. The chemo-PDT activity was significantly less in non-tumorigenic lung epithelial cells (Beas-2B). The prodrug effectively triggered cellular apoptosis, which was confirmed by the Annexin V-FITC/propidium iodide assay, and the alteration of the mitochondrial membrane potential was substantiated by the JC-1 dye assay. The ß-tubulin immunofluorescence assay confirmed that incubating the cells with a light-treated complex resulted in the rapture of the cytoskeletal structure and the formation of apoptotic bodies. The results demonstrate that the prodrug triggered apoptosis via DNA damage, a reduction in mitochondrial function and disruption of the cytoskeletal framework.

Investigation of the Impact of L-Phenylalanine and L-Tyrosine Pre-Treatment on the Uptake of 4-Borono-L-Phenylalanine in Cancerous and Normal Cells Using an Analytical Approach Based on SC-ICP-MS.

Boron has gained significant attention in medical research due to its B-10 isotope's high cross section for the reaction with thermal neutrons, generating ionizing particles that can eliminate cancer cells, propelling the development of boron neutron capture therapy (BNCT) for cancer treatment. The compound 4-borono-L-phenylalanine (BPA) has exhibited potential in BNCT clinical trials. Enhancing BPA uptake in cells involves proposing L-amino acid preloading. This study introduces a novel analytical strategy utilizing ICP-MS and single cell ICP-MS (SC-ICP-MS) to assess the effectiveness of L-tyrosine and L-phenylalanine preloading on human non-small cell lung carcinoma (A549) and normal Chinese hamster lung fibroblast (V79-4) models, an unexplored context. ICP-MS outcomes indicated that L-tyrosine and L-phenylalanine pre-treatment increased BPA uptake in V79-4 cells by 2.04 ± 0.74-fold (p = 0.000066) and 1.46 ± 0.06-fold (p = 0.000016), respectively. Conversely, A549 cells manifested heightened BPA uptake solely with L-tyrosine preloading, with a factor of 1.24 ± 0.47 (p = 0.028). BPA uptake remained higher in A549 compared to V79-4 regardless of preloading. SC-ICP-MS measurements showcased noteworthy boron content heterogeneity within A549 cells, signifying diverse responses to BPA exposure, including a subset with notably high BPA uptake. This study underscores SC-ICP-MS's utility in precise cellular boron quantification, validating cellular BPA uptake's heterogeneity.

Proteomic Analysis of Rat Duodenum Reveals the Modulatory Effect of Boron Supplementation on Immune Activity.

The proper supplementation of boron, an essential trace element, can enhance animal immune function. We utilized the method of TMT peptide labeling in conjunction with LC-MS/MS quantitative proteomics for the purpose of examining the effects of boric acid on a rat model and analyzing proteins from the duodenum. In total, 5594 proteins were obtained from the 0, 10, and 320 mg/L boron treatment groups. Two hundred eighty-four proteins that exhibit differential expression were detected. Among the comparison, groups of 0 vs. 10 mg/L, 0 vs. 320 mg/L, and 10 vs. 320 mg/L of boron, 110, 32, and 179 proteins, respectively, demonstrated differential expression. The results revealed that these differential expression proteins (DEPs) mainly clustered into two profiles. GO annotations suggested that most of the DEPs played a role in the immune system process, in which 2'-5'-oligoadenylate synthetase-like, myxovirus resistance 1, myxovirus resistance 2, dynein cytoplasmic 1 intermediate chain 1, and coiled-coil domain containing 88B showed differential expression. The DEPs had demonstrated an augmentation in the signaling pathways, which primarily include phagosome, antigen processing, and presentation, as well as cell adhesion molecules (CAMs). Our study found that immune responses in the duodenum were enhanced by lower doses of boron and that this effect is likely mediated by changes in protein expression patterns in related signaling pathways. It offers an in-depth understanding of the underlying molecular mechanisms that lead to immune modulation in rats subjected to dietary boron treatment.

Boron-resistant Alternaria alternata (OG14) mitigates boron stress by improving physiological and antioxidative response in wheat (Triticum aestivum L.).

Effect of Alternaria alternata (OG14) isolated from a rock lichen (Xanthoria sp.) was investigated on the relief of boron stress in wheat. To determine the tolerance level to B stress, the fungus was grown at increasing boric acid (BA) concentrations in the range of 0.0-2.5 M. No significant change in colony development of the fungus was observed up to 1 M BA application compared to the control but after this dose, it decreased depending on the increase in the BA dose. When the element content of wheat seedlings was evaluated by ICP-MS, BA application increased B content together with Mg, P, K, Fe contents of the seedlings to very high levels compared to the control. However, fungus + BA treatments decreased the content of B and the other elements in the seedlings. The BA applications resulted in an increase in the levels of reactive oxygen species, including H2O2 and O2.-as well as lipid peroxidation in the seedlings. However, when the fungal inoculation was performed under the same BA conditions, the levels of these parameters decreased. The fungus inoculation stimulated the activity of all studied enzymes compared to BA applications. BA applications alone increased non - enyzmatic the oxidized ascorbate level more than the reducing ascorbate, leading to a decrease in the AsA/DHA ratio. The results show that A. alternata treatment can mitigate the negative effects of B stress on wheat seedlings by reducing ROS, LPO, B content, increasing the capacity of enzymatic and non-enzymatic antioxidants, and improving root and shoot length.

Therapeutic role of boron on acrylamide-induced nephrotoxicity, cardiotoxicity, neurotoxicity, and testicular toxicity in rats: Effects on Nrf2/Keap-1 signaling pathway and oxidative stress.

BACKGROUND: Acrylamide (ACR) is a heat-related carcinogen used in cooking some foods as well as in other thermal treatments. The present study aims to investigate the possible protective effect of boron (BA) against ACR-induced toxicity of kidney, brain, heart, testis, and bladder tissues in rats. METHODS: Rats have been divided into 5 equal groups: Control (saline), ACR (38.27 mg/kg), BA (20 mg/kg), BA+ ACR (10 mg/kg + ACR), and BA+ ACR (20 mg/kg BA+ACR). Kidney tissue from rats was collected and the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of superoxide dismutase (SOD) were measured. In addition, the kidneys of these animals, as well as the brain, heart, testes, and bladder tissues were examined for possible histological changes. Total Nrf2 and Keap-1 protein expression in kidney, heart, and testis tissues was examined by immunohistochemistry. RESULTS: While significant increases in MDA levels were observed in the kidneys of rats receiving ACR alone, significant decreases in antioxidant markers (SOD and GSH) were observed. Besides, kidney, brain, heart, and testicular tissues were analyzed and damage was observed in the groups receiving ACR. However, no significant histologic changes were noted in the bladder tissue. Both dosages of BA in combination with ACR improved the changes in ACR-induced antioxidant tissue parameters. Despite the fact that MDA levels were decreased with these two dosages, histological structural abnormalities were found to be greatly improved. CONCLUSION: Our results show that BA has a strong protective effect on ACR-induced multi-organ toxicity. The study results show that BA could be a potential element to reduce ACR toxicity to which we are often exposed.

Evaluation of the effect of boron derivatives on cardiac differentiation of mouse pluripotent stem cells.

BACKGROUND: The heart is one of the first organs to form during embryonic development and has a very important place. So much that the formation of a functional heart is completed on the 55th day of human development and the 15th day of mouse development. Myocardial, endocardial and epicardial cells, which are derived from the mesoderm layer, are the cells that form the basis of the heart. Cardiac development, like other embryonic developments, is tightly controlled and regulated by various signaling pathways. The WNT signaling pathway is the most studied of these signaling pathways and the one with the clearest relationship with heart development. It is known that boron compounds and the Wnt/ß-catenin pathway are highly correlated. Therefore, this study aimed to investigate the role of boron compounds in heart development as well as its effect on pluripotency of mouse embryonic stem cells for the first time in the literature. METHODS: Toxicity of boron compounds was evaluated by using MTS analysis and obtained results were supported by morphological pictures, Trypan Blue staining and Annexin V staining. Additionally, the possible boron-related change in pluripotency of embryonic stem cells were analyzed with alkaline phosphatase activity and immunocytochemical staining of Oct4 protein as well as gene expression levels of pluripotency related OCT4, SOX2 and KLF4 genes. The alterations in the embryonic body formation capacity of mouse embryonic stem cells due to the application boron derivatives were also evaluated. Three linage differentiation was conducted to clarify the real impact of boron compounds on embryonic development. Lastly, cardiac differentiation of mESCs was investigated by using morphological pictures, cytosolic calcium measurement, gene expression and immunocytochemical analysis of cardiac differentiation related genes and in the presence of boron compounds. RESULTS: Obtained results show that boron treatment maintains the pluripotency of embryonic stem cells at non-toxic concentrations. Additionally, endodermal, and mesodermal fate was found to be triggered after boron treatment. Also, initiation of cardiomyocyte differentiation by boron derivative treatments caused an increased gene expression levels of cardiac differentiation related TNNT2, Nkx2.5 and ISL-1 gene expression levels. CONCLUSION: This study indicates that boron application, which is responsible for maintaining pluripotency of mESCs, can be used for increased cardiomyocyte differentiation of mESCs.

The effect of the boron-based gel on the treatment of diabetic foot ulcers: A prospective, randomized controlled trial.

BACKGROUND: Chronic ulcers represent impaired healing capacity with high mortality in the elderly or patients with systemic disorders such as diabetes. Boron is an effective agent in wound healing by promoting cell migration and proliferation and reducing inflammation in the wound area. This study aimed to evaluate the therapeutic effect of a sodium pentaborate-based topical formulation compared to control on the treatment of diabetic foot ulcers. METHODS: A prospective, double-blind, randomized controlled trial was conducted to apply randomly the topical sodium pentaborate 3% gel or topical conventional remedy (control) by patients diagnosed with diabetic foot ulcers. The 171 eligible participants aged 18-75 years received the allocated medicines twice a day for a month with an allocation ratio of 3:1. Twenty-five days and two months after the end of the trial, participants were reinvestigated for their ulcer condition and any recurrence. Wagner's classification of diabetic foot ulcers was applied to this purpose (0-5). RESULTS: 161 participants (57 females, 104 males; mean age: 59.37) completed this study. After the intervention, most participants in the intervention group had a lower ulcer grade than the control group (adjusted mean difference (95% CI): - 0.91 (-1.1 to -0.73); p < 0.001). Moreover, most participants in the intervention group (n = 109 (90.8%)) were treated at a higher rate than the control group (n = 5 (12.2%)) after intervention (adjusted odds ratio (95% CI): 0.008 (0.002-0.029); p < 0.001). There was no case of recurrence in the intervention group while its rate was (n = 2 (40%)) in the control group (p < 0.001). CONCLUSION: The present study suggests that topical sodium pentaborate gel may help treat and decrease the grade of diabetic foot ulcers and prevent the recurrence of diabetic foot ulcers.

The effects of boron on some biochemical parameters: A review.

BACKGROUND: Boron; It is used mainly in glass and ceramics, in the defense industry, in jet and rocket fuel, as a disinfectant, and even in the agricultural sector to increase or prevent vegetation development. Its use in the health field has become more widespread when studies in recent years are reviewed. Although it has been reported that boron has essential biological effects on minerals, some enzymes, and hormones, the mechanism of these biological effects has yet to be fully elucidated. This review aims to bring a new perspective to researchers by combining the results of experimental studies in the literature on the effects of boron on some biochemical parameters. METHODS: Works of literature on boron were brought together using more than one database (WOS, PubMed, Scopus, Google Scholar). The animal, boron type and dose used in the experimental study, and biochemical parameters (glucose, urea, BUN (blood urea nitrogen), uric acid, creatinine, creatine kinase, blood lipid profile, minerals, liver function tests) were systematically compiled. RESULTS: It was observed that the studies mainly focused on glucose and lipid profiles and had a lowering effect on these parameters. From a mineral point of view, the studies are mostly related to the bone matrix. CONCLUSION: Although the mechanism of action of boron on biochemical parameters has not yet been clarified, it would be beneficial to examine its relationship with hormones in more depth. A good understanding and analysis of the effect of boron, which is widely used, on biochemical parameters will be beneficial in taking necessary precautions for human and environmental health.