Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives.

Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). As a dietary supplement, NR appears to be well tolerated, having better pharmacodynamics and greater potency. Unfortunately, NR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Recently, work related to prebiotic chemistry discovered that NR borate is considerably more stable than NR itself. However, immediately upon consumption, the borate dissociates from the NR borate and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NR left behind is expected to behave pharmacologically in ways identical to NR itself. This review provides a comprehensive summary (through Q1 of 2023) of the literature that makes the case for the consumption of NR as a dietary supplement. It then summarizes the challenges of delivering quality NR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NR borate in these processes.

Zinc-Boron-PLGA biocomposite material: preparation, structural characterization, and in vitro assessment.

Nowadays, the state-of-the-art discoveries in the field of delivery systems for therapeutic purposes have redefined the importance of biocompatible and biodegradable poly(lactic-co-glycolic acid (PLGA) nanocomposites. The study aimed to obtain a biocomposite material, with improved properties of its constituents [zinc-boron (Zn-B) complex and PLGA], by a simple, cost-effective method. The water∕oil∕water double emulsion technique allowed the adjustment of the synthesis parameters, to maximize the degree of Zn-B complex encapsulation. The morphological aspects of the samples were established by scanning electron microscopy (SEM). Particle size distribution was determined by dynamic light scattering (DLS). Morphology was typical for PLGA, spherical one. Depending on the synthesis conditions, the obtained particles have diameters between 10-450 nm. Zeta potential (ZP) showed that the particles have electronegative surface charge, offering a favorable perspective on aggregation, flocculation, and dispersion phenomena. It was observed, applying the design of experiments, that the particles size increased with increasing amounts of PLGA and polyvinyl alcohol (PVA), while ZP increased with higher PLGA and smaller PVA amounts in the formulation. The encapsulation efficiency was determined by ultra-high performance liquid chromatography∕mass spectrometry (UHPLC∕MS). The in vitro assessment was performed using Vero CCL-81 epithelial cell line and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Zn-B-PLGA biocomposite has promising characteristics and can be used for future biomedical applications.

Biocompatibility Studies on a Collagen-Hydroxyapatite Biomaterial.

The current treatment of osteomyelitis includes systemic antibiotic therapy and a debridement procedure of the formed biofilm and necrotic tissue. Moreover, cements and three-dimensional scaffolds are used both for the delivery of therapeutic agents and as fillers for bone defects. The aim of our research was to test, on cellular cultures, the biocompatibility of a previously synthesized microporous biocomposite containing hydroxyapatite and a collagen matrix including a therapeutic agent (ciprofloxacin and gentamicin). The scaffold was obtained by direct mineralization namely co-precipitation of hydroxyapatite on a collagen matrix.

New Insights into Boron Essentiality in Humans and Animals.

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for some bacteria, plants, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, and brain function. Naturally organic B (NOB) species may become promising novel prebiotic candidates. NOB-containing compounds have been shown to be essential for the symbiosis between organisms from different kingdoms. New insights into the key role of NOB species in the symbiosis between human/animal hosts and their microbiota will influence the use of natural B-based colon-targeting nutraceuticals. The mechanism of action (MoA) of NOB species is related to the B signaling molecule (autoinducer-2-borate (AI-2B)) as well as the fortification of the colonic mucus gel layer with NOB species from B-rich prebiotic diets. Both the microbiota and the colonic mucus gel layer can become NOB targets. This paper reviews the evidence supporting the essentiality of the NOB species in the symbiosis between the microbiota and the human/animal hosts, with the stated aim of highlighting the MoA and targets of these species.

Simultaneous Determination of Two Tyrosine Kinase Inhibitors in Tablets by HPLC-MS analysis.

The class of tyrosine kinase inhibitors (TKIs) is represented by a group of compounds which are currently used in the treatment of different types of cancer. These oral medicines present a narrow therapeutic index and a large inter-and intra-individual variability. Within this work, a simple, accurate and rapid reversed phase ultra-high-performance liquid chromatographic (RP-UHPLC) method with mass spectrometric (MS) detection for simultaneous analysis of two TKIs, ibrutinib and ruxolitinib, using pentoxifylline as internal standard (IS) in tablet dosage forms is presented. The separation was carried out on a Waters (Milford, Massachusetts, USA) Arc System coupled with a Waters QDa mass detector. The column used was a Waters CORTECS C18 (4.6×50mm, 2.7µm); a gradient elution was carried out using a mixture of ammonium formate 10 mM aqueous solution and acetonitrile. The flow rate of the mobile phase was set to 0.5mL/min. The column temperature was equilibrated to 40°C. The injected volume was 5µL. All samples were kept at 20°C during the entire analysis. Mass spectra were recorded in positive ionization mode in the range of m/z 100-400 for ruxolitinib and m/z 100-500 for ibrutinib. Quantification was established in single ion recording (SIR) mode for each compound, using pentoxifylline as internal standard. The method was validated according to International Guidelines in terms of stability, limit of detection, limit of quantitation, linearity, precision and accuracy. The validated method can be successfully applied for simultaneous determination of TKIs in tablet dosage forms.

Boron-containing compounds in Dentistry: a narrative review.

Research on the use of boron (B) in the field of oral health has gained momentum in recent years, with various studies on the possibilities of using various B-containing compounds (BCCs). A multitude of applications have been discovered, from cariostatic activity to anti-inflammatory and antifungal activity, paving the way for other new research directions. B is a microelement that is commonly found in the human diet, and present throughout the body, with the highest concentration in the structure of bones, teeth, and gastrointestinal mucus gel layer. Multiple studies have demonstrated that B plays some important roles, especially in bone development and recently has been proposed to have an essential role in the healthy symbiosis. In addition, B has also attracted the interest of researchers, as various studies used BCCs in conventional or modern biomaterials. In this review, we have brought together the information we have found about B updates in the dental field and analyzing its future perspectives and potential for further studies.

Calcium fructoborate coating of titanium-hydroxyapatite implants by chemisorption deposition improves implant osseointegration in the femur of New Zealand White rabbit experimental model.

BACKGROUND: The identification of biocomposites that improve cell adhesion and reduce bone integration time is a great challenge for implantology and bone reconstruction. AIM: Our aim was to evaluate a new method of chemisorption deposition (CD) for improving the biointegration of hydroxyapatite-coated titanium (HApTi) implants. CD method was used to prepare a calcium fructoborate (CaFb) coating on a HApTi (HApTiCaFb) implant followed by evaluation of histological features related to bone healing at the interface of a bioceramic material in an animal model. METHODS: The coating composition was investigated by high-performance thin-layer chromatography/mass spectrometry. The surface morphology of the coating was studied by scanning electron microscopy (SEM), before and after the in vitro study. We implanted two types of bioceramic cylinders, HApTi and HApTiCaFb, in the femur of 10 New Zealand White (NZW) rabbits. RESULTS: The release of CaFb from HApTiCaFb occurred rapidly within the first three days after phosphate-buffered saline immersion; there was then a linear release for up to 14 days. SEM analysis showed similar morphology and particle size diameter for both implants. Around the porous HApTiCaFb implant, fibrosis and inflammation were not highlighted. CONCLUSIONS: Easily applied using CD method, CaFb coatings promote HApTi implant osseointegration in the femur of NZW rabbits.

The Fructoborates: Part of a Family of Naturally Occurring Sugar-Borate Complexes-Biochemistry, Physiology, and Impact on Human Health: a Review.

Sugar-borates (SBs) are mono- or di-sugar-borate esters (SBEs) comprised of one or two monosaccharide molecules linked to a boron (B) atom. SBEs occur naturally in commonly consumed herbs, vegetables, fruits, seeds, and nuts and, other than greatly varying levels of B found in local drinking water, are the primary natural dietary sources of B-containing molecules in humans. To date, the most studied SBE is calcium fructoborate (CaFB). CaFB represents an important example of how organic B-containing molecules are significantly distinct from their inorganic counterparts. During these past two decades, CaFB has been researched for its physical and biochemical characteristics, safety, and clinical outcomes. Results of these researches are presented and discussed herein. CaFB has been characterized using Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), high-performance thin-layer chromatography (HPTLC), nuclear magnetic resonance (NMR), liquid chromatography-multistage accurate mass spectrometry (LC-MSn), X-ray diffraction (XRD), Raman spectroscopy, and inductively coupled plasma (ICP) in non-biological and biological specimens. Potential health benefits of CaFB have been clinically investigated in pilot and efficacy studies demonstrating (i) significant reductions in knee discomfort and improved flexibility within 7, 14, and 90 days and (ii) significant effect on blood levels of inflammatory, cardiovascular, and other biomarkers. These studies support the use of CaFB as a dietary supplement for the management of joint discomfort. CaFB is presented here in order to illustrate how physiological benefits are imparted by distinct organic boron-containing molecules rather than solely by the element B itself. Considering recent National Health and Nutrition Examination Survey (NHANES) data reporting increases in age-related joint pain and an increasing elderly demographic, SBEs offer potential for safe, natural, and effective management of joint discomfort and improved mobility in human and animal health applications. Several of these studies may also open new opportunities for use of SBEs for health benefits beyond joint health.

Effects of boron-containing compounds on cardiovascular disease risk factors - A review.

Boron is considered to be a biological trace element but there is substantial and growing support for it to be classified as an essential nutrient for animals and humans, depending on its speciation. Boron-containing compounds have been reported to play an important role in biological systems. Although the exact biochemical functions of boron-containing compounds have not yet been fully elucidated, previous studies suggest an active involvement of these molecules in the mediation of inflammation and oxidative stress. Chronic inflammation and oxidative stress are known to amplify the effects of the main cardiovascular risk factors: smoking, diet, obesity, arterial hypertension, dyslipidemia, type 2 diabetes (as modifiable risk factors), and hyperhomocysteinemia and age (as independent risk factors). However, the role of boron-containing compounds in cardiovascular systems and disease prevention has yet to be established. This paper is a review of boron-containing compounds' existence in nature and their possible functions in living organisms, with a special focus on certain cardiovascular risk factors that may be diminished by intake of these compounds, leading to a reduction of cardiovascular morbidity and/or mortality.

Hydroxyapatite-ciprofloxacin delivery system: Synthesis, characterisation and antibacterial activity.

The main objective of this study was to synthesize hydroxyapatite-ciprofloxacin composites using a chemical precipitation method and to evaluate the properties and in vitro release profile of the drug from the hydroxyapatite-ciprofloxacin composites. Composite characterization was achieved by FT-IR, XRD and DLS. Ciprofloxacin determination was accomplished by HPLC, resulting in good incorporation efficiency of the drug (18.13 %). The in vitro release study (Higuchi model C = K t1/2 and Ritger-Peppas model, C = K t0.6) showed a diffusion-controlled mechanism. The antibacterial activity showed that the bacterial growth inhibition zones were approximately equal for the synthesis composites and for the mechanical mixture on the Staphylococcus aureus germ. The use of hydroxyapatite, which is a biocompatible, bioactive and osteoconductive material, with ciprofloxacin, which has good antibacterial activity in this composite, makes it suitable for the development of bone grafts. Furthermore, the synthesis process allows a slow local release of the drug.

Simultaneous Quantitation of Boric Acid and Calcium Fructoborate in Dietary Supplements by HPTLC-Densitometry.

The paper describes a new, simple, selective and precise high-performance thin-layer chromatographic (HPTLC) method for the simultaneous identification and quantitative determination of boric acid (BA) and calcium fructoborate (CFB) in bulk and tablet/capsule dosage forms of dietary supplements. HPTLC silica gel G 60 F254 precoated glass plates were used as the stationary phase. The mobile phase consisted of 2-propanol-water 8:2 (v/v). The two boron-based compounds were adequately separated with the Rf values of 0.83 ± 0.01 (BA) and 0.59 ± 0.01 (CFB).

Calcium Fructoborate for Bone and Cardiovascular Health.

Calcium fructoborate (CF), a natural sugar-borate ester found in fresh fruits and vegetables, is a source of soluble boron. CF contains three forms of borate (diester, monoester, and boric acid) and all are biologically active, both at the intracellular (as free boric acid) and extracellular level (as fructose-borate diester and monoester). At the cellular and molecular level, CF is superior to the boric acid/borate, exhibiting a complex "protective" effect against inflammatory response. CF is commercially available in the USA as a "nature-identical" complex, an active compound for dietary supplements. It provides effective and safe support against the discomfort and lack of flexibility associated with osteoarticular conditions (arthritis and joint degeneration), and improves Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill indexes. In addition, orally administered CF is effective in ameliorating symptoms of physiological response to stress, including inflammation of the mucous membranes, discomfort associated with osteoarthritis disorders, and bone loss, and also for supporting cardiovascular health. Clinical studies have exhibited the ability of CF to significantly modulate molecular markers associated with inflammatory mechanisms, mainly on the elevated serum levels of C-reactive protein (CRP).

Effects of Calcium Fructoborate on Levels of C-Reactive Protein, Total Cholesterol, Low-Density Lipoprotein, Triglycerides, IL-1ß, IL-6, and MCP-1: a Double-blind, Placebo-controlled Clinical Study.

Calcium fructoborate (CFB) has been reported as supporting healthy inflammatory response. In this study, we assess the effects of CFB on blood parameters and proinflammatory cytokines in healthy subjects. This was a randomized, double-blinded, placebo-controlled trial. Participants received placebo or CFB at a dose of 112 mg/day (CFB-1) or 56 mg/day (CFB-2) for 30 days. Glucose, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), C-reactive protein (CRP), homocysteine, interleukin 1 beta (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1) were determined before and after supplementation. CFB-1 showed a reduction in blood levels of CRP by 31.3 % compared to baseline. CFB-1 and CFB-2 reduced LDL levels by 9.8 and 9.4 %, respectively. CFB-1 decreased blood homocysteine by 5.5 % compared with baseline, whereas CFB-2 did not have a significant effect. Blood levels of TG were reduced by 9.1 and 8.8 % for CFB-1 and CFB-2, respectively. Use of both CFB-1 and CFB-2 resulted in significantly reduced IL-6 levels, when compared within and between groups. IL-1ß was reduced by 29.2 % in the CFB-1 group. Finally, CFB-1 and CFB-2 reduced MCP-1 by 31 and 26 %, respectively. Our data indicate that 30-day supplementation with 112 mg/day CFB (CFB-1) resulted in a significant reduction of LDL, TG, TC, IL-1ß, IL-6, MCP-1, and CRP. HDL levels were increased, when compared to baseline and placebo. These results suggest that CFB might provide beneficial support to healthy cardiovascular systems by positively affecting these blood markers (ClinicalTrials.gov, ISRCTN90543844; May 24, 2012 ( http://www.controlled-trials.com/ISRCTN90543844 )).

Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study.

A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 × 4.6 mm; 5 µm) via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium) buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid) : acetonitrile : methanol with flow rate of 1 mL·min(-1). Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008-2 µg·mL(-1) for clopidogrel, 0.01-4 µg·mL(-1) for its carboxylic acid metabolite, and 0.005-2.5 µg·mL(-1) for atorvastatin. The results of accuracy (as recovery) with ibuprofen as internal standard were in the range of 96-98% for clopidogrel, 94-98% for its carboxylic acid metabolite, and 90-99% for atorvastatin, respectively.

Differentiation of mesenchymal stem cells onto highly adherent radio frequency-sputtered carbonated hydroxylapatite thin films.

In this work, an improved version of the radio frequency magnetron sputtering (RF-MS) technique was used to prepare highly adherent B-type carbonated hydroxylapatite (B-CHA) thin films. Fourier transform infrared spectroscopy (FTIR) and grazing incidence X-ray diffraction studies proved that the coatings maintained the composition and revealed the polycrystalline structure of HA. Scanning electron microscopy analysis showed that the CHA films are rough and exhibit a homogeneous microstructure. Energy-dispersive X-ray spectroscopy (EDX) mapping demonstrated a uniform distribution of the Ca and P cations while a Ca/P ratio of 1.8 was found. In addition, the FTIR experiments showed a remarkable reproducibility of the nanostructures. Human mesenchymal stem cells (hMSCs), in vitro differentiated osteoblasts, and explanted bone cells were grown over the surface of CHA coatings for periods between a few hours and 21 days. Osteoprogenitor cells maintained viability and characteristic morphology after adhesion on CHA coatings. Ki67-positive osteoblasts were the evidence of cell proliferation events. Cells showed positive staining for markers of osteoblast phenotype such as collagen type I, bone sialoprotein and osteonectin. Our data showed the formation of mineralized foci by differentiation of hMSCs to human primary osteoblasts after cultivation in osteogenic media on RF-sputtered films. The results demonstrate the capacity of B-type CHA coating to support MSCs adhesion and osteogenic differentiation ability.