A versatile ratiometric fluorescence nanoprobe for the determination of clonazepam in patients' plasma samples.

Despite the necessity of the study of therapeutic drug monitoring of clonazepam (CLZ), there are only a few fast detection methods available for determining CLZ in biological media. This study aims to develop a cost-effective and ratiometric probe for the quantification of CLZ in plasma samples. Fluorescent polydopamine nanoparticles were produced through a self-polymerization process at a pH of 8.5. Rhodamine B molecules were employed as a fluorescent reference material, emitting stable fluorescence in the visible range. The fabricated probe exhibited a specific detection capability for CLZ. The fluorescence emission of the probe was enhanced in two concentration ranges: from 50 ng/mL to 1.0 µg/mL and from 1.0 to 15.0 µg/mL with a lower limit of quantification of 50 ng/mL, indicating the sensitivity of the probe for detecting CLZ plasma levels. The accuracy of the probe is favorable which could be recommended for CLZ monitoring in the biological media. Furthermore, this probe is highly specific towards CLZ in the presence of various interfering agents which is mainly caused by its ratiometric nature. The developed platform showed high reliability in quantifying CLZ concentrations in patients' plasma samples. Hence, the fabricated probe could be recommended as a reliable method for the routine detection of CLZ in clinical settings.

Detection of pioglitazone based on dual-emission ratiometric fluorescence probe consisting of ZIF8 and to L-ASC-AuNP/DA nanoparticles.

A simple and sensitive dual-emission ratiometric fluorescent probe was developed using zeolitic imidazolate framework 8 (ZIF8) and L-ascorbic acid Au-doped dopamine nanoparticles (ZIF8/L-ASC-AuNP/DA NP) for the determination of pioglitazone (Pio), an oral hypoglycemic agent and insulin sensitizer, in real samples. The prepared system was based on the Pio-enhanced dual-emission intensity of ZIF8/L-ASC-AuNP/DA NP. The potential impact of various parameters on the system's emission intensity was tested. According to the findings, there is a strong linear correlation between the system's turn-on fluorescence intensity and Pio concentrations in the range 0.3 nM to 30.0 µM. The obtained value for the limit of detection (LOD) was 0.14 nM. In addition, the intra- and inter-day accuracy of the nanoprobe was studied and the findings revealed satisfactory precision and accuracy of the system. The short-term and freeze-thaw stability of Pio in plasma samples was evaluated and the results indicated the high stability of the developed nanoprobe under the test conditions. Pio was accurately detected in human plasma samples under ideal conditions with analytical recoveries in the range 86.0 - 109.3%. The results showed that the devised probe may be employed as an easy, sensitive, and precise approach for detecting Pio in real samples.

Spectroscopic aspects on the interaction of nisin with serum albumin: thermodynamic and kinetic studies.

Introduction: Nisin is a bacteriocin produced by Streptococcus and Lactococcus species and has antimicrobial activity against other bacteria. Nisin omits the need to use chemical preservatives in food due to its biological preserving properties. Methods: In the present in vitro study, we investigated nisin interaction with bovine serum albumin (BSA) using fluorescence spectroscopy and surface plasmon resonance (SPR) analysis to obtain information about the mechanisms of BSA complex formation with nisin. Results: The BSA fluorescence intensity values gradually diminished with rising nisin concentration. The BSA fluorescence quenching analysis indicated that a combined quenching mechanism plays the main role. Finally, the Kb values were reduced with increasing temperature, which is demonstrative of nisin-BSA complex stability decrease at high temperatures. The negative values of ΔH° and ΔS° showed that hydrogen bonds and van der Waals forces are the foremost binding force between BSA and nisin. Meanwhile, the negative values of ΔG° demonstrated the exothermic and random nature of the reaction process. The results of the SPR verified the gained results through the fluorescence spectroscopy investigation, which denoted that the BSA affinity to nisin diminished upon increasing temperature. Conclusion: Overall, fluorescence spectroscopy and SPR results showed that the BSA interaction with nisin decreased with rising temperatures.

The influence of advanced materials on the analytical performance of semiconductor-based gas sensors.

Chemiresistive gas sensors are metal oxide-based sensors that have received significant attention in different fields. Ambient gas sensors are especially important in the fabrication of wearable probes for the real-time detection of biomarkers in human body samples. Usually, room temperature sensors are affordable due to their low power consumption, resulting in simple instrumentation and maintenance. To fabricate versatile gas sensors, i.e. sensitive, selective, ambient temperature operating gas sensors, and improve the sensing performance of the traditionally used sensor, new materials play an important role. In other words, new advanced materials are essential for designing and fabricating new gas sensors. Hence, in this review, the application and impact of new advanced materials in the fabrication of reliable gas sensors are discussed in detail. Special emphasis is given to the effect of new materials in the fabrication of room-temperature operating systems. Finally, future research outlook and possible challenges that may be encountered by reliable gas sensors are also explained.

In-situ preparation of norepinephrine-functionalized silver nanoparticles and application for colorimetric detection of tacrolimus in plasma samples.

Tacrolimus (Tac) is a well-documented immunosuppressive agent for the prevention of graft-vs-host diseases in several types of organ transplants. The narrow therapeutic window and the individual-variable pharmacokinetics of Tac demonstrate the importance of regular therapeutic drug monitoring (TDM) as an imperative concept for its oral medication regimens. A simple, one-step, selective, and sensitive colorimetric platform is fabricated for the determination of Tac by surface modification of the silver nanoparticles (AgNPs) via norepinephrine (NE) molecules. The attachment of NE and Tac induces the aggregation of the AgNPs, which is observed by color distinction (yellow to brown) and a noteworthy shifting of the absorption peak in the visible region. The fabricated nanoprobe can detect Tac concentrations in plasma samples in two linear ranges from 2 ng/mL to 70 ng/mL and 70 ng/mL to 1000 ng/mL with R2 > 0.99. The limit of detection (LOD) was calculated as low as 0.1 ng/mL. The developed method was applied for the determination of Tac in patient's plasma samples under Tac medication therapy.

A ratiometric electrochemical probe for the quantification of apixaban in unprocessed plasma samples using carbon aerogel/BFO modified glassy carbon electrodes.

A novel electrochemical probe was established for the quantification of apixaban (APX) in unprocessed plasma samples. Efficiently oxidized graphene oxide aerogels (EEGO-AGs) and nano-sized Bi2Fe4O9 (BFO) particles were electrodeposited on the surface of a glassy carbon electrode (GCE). In this work, a ratiometric electrochemical method was introduced for APX detection to enhance the specificity of the probe in plasma samples. The fabricated ratiometric probe was employed for the indirect detection determination of APX using K3[Fe(CN)6]/K4[Fe(CN)6] as the redox pair. The differential pulse voltammetry technique was used to record the current alteration of the BFO/EEGO-AG-functionalized GCE probe at various APX concentrations. The probe response was proportional to the APX concentrations from 10 ng mL-1 to 10 µg mL-1 with a low limit of quantification (LLOQ) of 10 ng mL-1. After validation, this method was successfully utilized for the determination of APX in patients' plasma samples who have taken APX regularly. The fabricated chemosensor detected APX concentrations in unprocessed plasma samples with high selectivity, resulting from the physical filtering antifouling activity of aerogels.

Electrochemical sensing of doxorubicin hydrochloride under sodium alginate antifouling conditions using silver nanoparticles modified glassy carbon electrodes.

Doxorubicin (DOX) is a highly effective anticancer drug with a narrow therapeutic window; thus, sensitive and timely detection of DOX is crucial. Using electrodeposition of silver nanoparticles (AgNPs) and electropolymerization of alginate (Alg) layers on the surface of a glassy carbon electrode, a novel electrochemical probe was constructed (GCE). The fabricated AgNPs/poly-Alg-modified GCE probe was utilized for the quantification of DOX in unprocessed human plasma samples. For the electrodeposition of AgNPs and electropolymerization of alginate (Alg) layers on the surface of GCE, cyclic voltammetry (CV) was used in the potential ranges of -2.0 to 2.0 V and -0.6 to 0.2 V, respectively. The electrochemical activity of DOX exhibited two oxidation processes at the optimum pH value of 5.5 on the surface of the modified GCE. The DPV spectra of poly(Alg)/AgNPs modified GCE probe toward consecutive concentrations of DOX in plasma samples demonstrated wide dynamic ranges of 15 ng/mL-0.1 µg/mL and 0.1-5.0 µg/mL, with a low limit of quantification (LLOQ) of 15 ng/mL. The validation results indicated that the fabricated electrochemical probe might serve as a highly sensitive and selective assay for the quantification of DOX in patient samples. As an outstanding feature, the developed probe could detect DOX in unprocessed plasma samples and cell lysates without the requirement for pretreatment.

Serum Levels of Indoxyl Sulfate and P-cresol in Type II Diabetic Patients With and Without Nephropathy.

INTRODUCTION: Indoxyl sulfate (IS) and para-cresol (p-cresol) are uremic toxins with high protein bonding index that accumulate in the body with decreasing kidney function. The main purpose of the current investigation was to compare the concentration of p-cresol and IS in serum of the type II diabetic individuals with and without nephropathy. METHODS: Fifty-five patients with type II diabetes mellitus were divided into two groups: case and control. The case group consisted of 26 diabetic patients with nephropathy (proteinuria and serum creatinine below 1.5 mg/dL) without any other kidney diseases. The control group included 29 patients without diabetic nephropathy. Patients with advanced heart disease, cerebrovascular accident and other inflammatory or infectious diseases were excluded. Five mL of venous blood was taken from each patient in the morning fasting state. Then other laboratory tests including serum uric acid and creatinine levels, serum urea nitrogen, lipids and glucose were measured by standard methods. P-Cresol and IS levels were measured by the spectrofluorimetric method after extraction. We also filled out a checklist with information regarding the duration of their disease, medication history (oral or injectable), and other demographic information. There were no significant differences between the two groups regarding the investigated factors Results. There were no significant difference among the investigated factors between the two groups (P > .05) except for the serum creatinine, proteinuria and estimated glomerular filtration rate, where the mean values of cases were considerably higher than those of the controls. Serum IS and p-cresol levels were also significantly higher in the case group (P < .05). CONCLUSION: According to the findings, it seems that IS, and p-cresol may play a role in the development of diabetic nephropathy and other complications of diabetes mellitus.  DOI: 10.52547/ijkd.7266.

Two-photon fluorescence probe for quantification of cyclosporine.

A novel ratiometric fluorescent sensor was fabricated for the fast and facile determination of cyclosporine A (CsA). Due to the narrow therapeutic index of CsA, its desired therapeutic effects are evident within a limited range of blood concentration, indicating the fundamental role of therapeutic drug monitoring in CsA pharmacological response. In this study, a two-photon fluorescence probe based on the zeolitic imidazolate framework (ZIF-8) and norepinephrine-capped silver nanoparticles (AgNPs@NE) was employed for the quantification of the CsA in human plasma samples. In the presence of CsA, the fluorescent emission intensity of ZIF-8-AgNPs@NE was quenched. Under the optimum conditions, the proposed probe determines CsA in plasma samples in two linear ranges of 0.01 to 0.5 µg mL-1 and 0.5 to 10 µg mL-1. The developed probe demonstrates the advantages of a facile and fast platform with limit of detection as low as 0.007 µg mL-1. At last, this method was applied to find CsA concentration in four patients receiving oral CsA regimen which indicates it as a promising method for on-site detection applications.

Dispersive solid-phase extraction of risperidone from plasma samples using graphene oxide aerogels and determination with liquid chromatography.

A graphene oxide-based aerogel was synthesized and applied to the extraction and the determinations with the high-performance liquid chromatography-ultraviolet detector. After the characterization of the produced graphene-aerogel, it was utilized as a dispersive solid-phase extraction sorbent for risperidone extraction from plasma samples. Aerogels are materials with a large surface area-to-mass ratio and plenty of core with functional groups which can easily attach to the analytes to extract them to the second phase. The suggested method determined risperidone in plasma samples in the wide dynamic range from 20 ng/ml to 3 µg/ml. The limits of detection and quantification of the developed method were calculated as 2.4 and 8.2 ng/ml, respectively. As a novel feature, the developed method has no need to precipitate plasma proteins, improving the analytical performance of the analysis. Also, for the first time, the produced materials were utilized for the extraction of risperidone from the plasma samples. The obtained results revealed that the developed approach could be employed as an accurate method for the quantification of risperidone in real plasma samples.

A dual-emission ratiometric fluorescent biosensor for ultrasensitive detection of glibenclamide using S-CDs/CdS quantum dots.

In the present work, sulfide-doped carbon dots (S-CDs)/cadmium sulfide quantum dots (CdS QDs) ratiometric fluorescent nanosensor has been developed for sensitive and selective determination of glibenclamide (GLC) in biological fluids. The method was based on the quenching effect of GLC on the dual-emission intensity of the S-CDs/CdS QDs system at 420 nm and 650 nm, which are related to S-CDs and CdS QDs, respectively. The fluorimetric data analysis indicated that the fluorescence signals of the system were quenched by adding GLC in a concentration-dependent manner. A good linear relationship was observed between GLC concentration and the quenched fluorescence intensity of the S-CDs/CdS QDs in the range of 0.3 nM-10.0 µM. The limit of detection (LOD) value was estimated to be 0.12 nM. Furthermore, under optimum conditions, GLC was detected in spiked human serum sample (as real media) using the developed ratiometric nanosensor with an accuracy of 99.6%. According to the results, the developed dual-emission system can be used as a reliable method for the quantitative detection of GLC in biological samples.

Synthesis and characterization of folate-functionalized silica-based materials and application for bioimaging of cancer cells.

Early-stage detection is a vital factor in the later treatment and prognosis of cancer. Enhancing the sensitivity and specificity of the cancer detection pathological and experimental approaches can affect the morbidity and mortality of this disease. A folic acid (FA)-functionalized silica quantum dots (SiQDs)/KCC-NH2@SiO2 nanomaterials were synthesized and characterized as a bioimaging agent of the MCF 7 cancer cells. These nanoparticles showed biocompatible nature with specificity towards folate receptor (FR)-overexpressed MCF 7 cancer cells. Viability findings suggested that the SiQDs/KCC-NH2@SiO2/FA nanomaterials have nontoxic nature towards the cells in the concentration of 200 µg/mL. Fluorescence microscopy images were utilized to estimate the cell internalization of the nanoparticles and further verified by the flow cytometry technique. The differentiation ability of the nanoparticles was also approved by incubation with FR-negative HEK 293 normal cells. The SiQDs/KCC-NH2@SiO2/FA nanoparticle exhibited high stability, bright and high quantum yield fluorescence emission, proposing as a high-quality material for in vivo bioimaging of FR-overexpressed circulating tumoral cancer cells (CTCs).

Applications of Advanced Materials for Non-Enzymatic Glucose Monitoring: From Invasive to the Wearable Device.

Diabetes mellitus (DM) is a global health problem leading to many complications and disabilities in life adjusting activities and even dead. Monitoring glucose levels is a key factor in diagnosis and management of DM. Conventional glucose sensors consisted of immobilized enzymes, are so susceptible to environmental conditions. In this way, nonenzymatic biosensors have attracted extensive attentions in many clinical diagnostics applications. To date, the finger pricking test is a common enzyme-based glucometer that is an invasive and inconvenient and may lead to infections in the injection sites. So, working on the possibility of cutaneous or subcutaneous insertion of devices as a noninvasive or minimally-invasive systems for continuous glucose controlling approaches through human biofluids (blood, perspiration, tears, saliva, etc.) have stimulated growing interest. This review summarizes recent nonenzymatic and noninvasive biofluids glucose monitoring systems which are highly resilience and stretchable to continuously adapt to body movements during common physical activity. Sensors are based on their constituent materials including carbon-based, metal nanoparticles, polymer, and hydrogel systems are classified for electrochemical, and optical glucose detection. Finally, we address the drawbacks and challenges of enzyme-free sensors which are aroused sustaining research passion to be used in point-of-care medical diagnostics applications.

Simple fluorescence chemosensor for the detection of calcium ions in water samples and its application in bio-imaging of cancer cells.

This article describes the design, synthesis and characterization of a sensor suitable for practical measurement of ionized calcium in water samples and cancer cells. Calcium is an important ion in living organs and works as a messenger in several cellular functions. A lack of Ca ions interrupts the immune system and can lead to several diseases. A novel magnetic-polydopamine nanoparticle (PDNP)/rhodamine B (RhB)/folic acid (FA) nanoparticle was developed for the determination of calcium ions in MCF 7 cell lysates and water samples. Furthermore, the produced nanoparticle was employed for bioimaging of folate receptor (FR)-overexpressed cancer cells. This nanoprobe displayed a bright photoluminescence emission at 576 nm under an excitation wavelength of 420 nm. In the presence of calcium ions, the fluorescence emission of the MNPs-PDNPs/RhB/FA probe was proportionally decreased from 20 ng mL-1 to 100 ng mL-1 and 0.5 µg mL-1 to 20 µg mL-1 with a lower limit of quantification (LLOQ) of about 20 ng mL-1. The developed sensor showed a low-interference manner in the presence of possible coexistence interfering ions. In addition, this nanomaterial showed excellent biocompatibility with favorable differentiation ability to attach to the FR-positive cancer cells. The MNPs-PDNPs/RhB/FA nanoparticle has been utilized for bioimaging of the MCF 7 cell with favorable differentiation ability.

Spectrofluorimetric Method for Monitoring Methotrexate in Patients' Plasma Samples and Cell Lysates Using Highly Fluorescent Carbon Dots.

For the first time, nitrogen, sulfur, phosphorus, and boron-doped carbon dots (N, S, P, B-codoped CDs) were synthesized through a hydrothermal reaction. The produced CDs were utilized to develop an optical sensor to determine methotrexate (MTX) in cell lysates and patients' plasma samples. Basically, in the presence of MTX, the fluorescence emission of the CD-based probe was quenched. Under optimum conditions, a good proportional relationship was obtained between the quenched fluorescence signal and MTX concentrations from 74.9 ng/mL to 99.9 µg/mL with a limit of detection of 74.9 ng/mL. The developed nanoprobe provided a wide linear range and high accuracy and was successfully utilized in the routine therapeutic drug monitoring of MTX in plasma samples. The obtained results proposed the developed nanoprobe for the on-time and specific detection of MTX in blood samples. As another application, N, S, P, B-codoped CDs were utilized for bioimaging MCF-7 cancer cells and could be proposed as efficient bioimaging agents for tumor cells.

Correlation of inflammatory biomarkers with the diversity of Bacteroidaceae, Bifidobacteriaceae, Prevotellaceae and Lactobacillaceae families in the intestinal microbiota of patients with end stage renal disease.

PURPOSE: Serum levels of inflammatory cytokines and uremic toxins, and their inter-correlations with the diversity of Bacteroidaceae, Bifidobacteriaceae, Prevotellaceae and Lactobacillaceae families in intestinal microbiota were investigated in patients with end stage renal disease (ESRD). METHODS: Stool and blood samples from 20 ESRD patients on maintenance hemodialysis were collected. DNA genome of the bacterial composition of the stool samples was extracted and evaluated by the sequencing analysis of 16S rRNA genes. Serum levels of inflammatory cytokines and uremic toxins were then analyzed. RESULTS: The mean serum concentrations of TNF-α, IL-6, indoxyl sulfate (IS) and p-cresol (PC) were 305.99 â€‹± â€‹12.03 â€‹ng/L, 159.95 â€‹± â€‹64.22 â€‹ng/L, 36.76 â€‹± â€‹5.09 â€‹µg/mL and 0.39 â€‹± â€‹0.15 â€‹µg/mL, respectively. The most significant positive correlation was observed between Prevotellaceae family and total antioxidant capacity (TAC), Lactobacilli species and CRP and PC, as well as Scardovia wiggsiae and IS (p â€‹< â€‹0.001). A negative correlation was also found between Bacteroides clarus and PC. Patients with ESRD on maintenance hemodialysis had elevated levels of PC and IS and increased levels of the inflammatory markers. The most positive correlation was found between microbiota and CRP and PC, while the most negative one was between microbiota and IL-1 and TAC. CONCLUSIONS: The abundance and diversity of Bacteroidaceae, Bifidobacteriaceae, Prevotellaceae and Lactobacillaceae families and their correlations with clinical parameters could provide benefits in the ESRD patients but they could not promote the symptoms.

A ratiometric fluorescent sensor for detection of metformin based on terbium-1,10-phenanthroline-nitrogen-doped-graphene quantum dots.

Metformin (MTF), an effective biguanide and oral antihyperglycemic agent, is utilized to control blood glucose levels in patients with type II diabetes mellitus, and the determination of its concentration in biological fluids is one of the main issues in pharmacology and medicine. In this work, highly luminescent nitrogen-doped graphene quantum dots (N-GQDs) were modified using terbium (Tb3+)-1,10-phenanthroline (Phen) nanoparticles (NPs) to develop a dual-emission ratiometric fluorescent sensor for the determination of MTF in biological samples. The synthesized N-GQDs/Tb-Phen NPs were characterized using different techniques to confirm their physicochemical properties. The N-GQDs/Tb-Phen NPs showed two characteristic emission peaks at 450 nm and 630 nm by exciting at 340 nm that belong to N-GQDs and Tb-Phen NPs, respectively. The results indicated that the emission intensity of both N-GQDs and Tb-Phen NPs enhanced upon interaction with MTF in a concentration-dependent manner. Also, a good linear correlation between the enhanced fluorescence intensity of the system and MTF concentration was observed in the range of 1.0 nM-7.0 µM and the limit of detection (LOD) value obtained was 0.76 nM. In addition, the prepared probe was successfully used for the estimation of MTF concentration in spiked human serum samples. In conclusion, the reported dual-emission ratiometric fluorescent sensor can be used as a sensitive and simple fluorimetric method for the detection of MTF in real samples.

Electromembrane extraction of tramadol from exhaled breath condensate and its liquid chromatographic analysis.

Tramadol has extracted from the exhaled breath condensate (EBC) samples through the supported liquid membrane consisting of 2-nitrophenyl octyl ether impregnated in the hollow fiber wall, and the lumen of the hollow fiber was filled with 20 µL of an acceptor phase. Under the optimum conditions of the electromembrane extraction, i.e. the stirring speed of 750 rpm, extraction time of 20 min, acceptor pH at 1.0, donor phase pH at 6.0, and an applied voltage of 170 V across the supported liquid membrane, a preconcentration factor of 128-fold with a extraction recovery of 64% was achieved. Acceptable linearity was obtained in the tramadol concentration range of 5-1000 ng mL-1 (R2 = 0.9999) with a limit of detection of 1.5 ng mL-1 and a limit of quantitation of 5 ng mL-1. The relative standard deviations for the intra-day and inter-day replications were obtained between 0.4% and 2.5%. The validated technique was successfully used to determine tramadol in real EBC samples.

Chitosan-based biomaterials for the treatment of bone disorders.

Bone is an alive and dynamic organ that is well-differentiated and originated from mesenchymal tissues. Bone undergoes continuous remodeling during the lifetime of an individual. Although knowledge regarding bones and their disorders has been constantly growing, much attention has been devoted to effective treatments that can be used, both from materials and medical performance points of view. Polymers derived from natural sources, for example polysaccharides, are generally biocompatible and are therefore considered excellent candidates for various biomedical applications. This review outlines the development of chitosan-based biomaterials for the treatment of bone disorders including bone fracture, osteoporosis, osteoarthritis, arthritis rheumatoid, and osteosarcoma. Different examples of chitosan-based formulations in the form of gels, micro/nanoparticles, and films are discussed herein. The work also reviews recent patents and important developments related to the use of chitosan in the treatment of bone disorders. Although most of the cited research was accomplished before reaching the clinical application level, this manuscript summarizes the latest achievements within chitosan-based biomaterials used for the treatment of bone disorders and provides perspectives for future scientific activities.