Development of biosensors for detection of fibrinogen: a review.

Fibrinogen as a major inflammation marker and blood coagulation factor has a direct impact on the health of humanity. The variations in fibrinogen content lead to risky conditions such as bleeding and cardiovascular diseases. So, accurate methods for monitoring of this glycoprotein are of high importance. The conventional methods, such as the Clauss method, are time consuming and require highly specialized expert analysts. The development of fast, simple, easy to use, and inexpensive methods is highly desired. In this way, biosensors have gained outstanding attention since they offer means for performing analyses at the points-of-care using self-testing devices, which can be applied outside of clinical laboratories or hospital. This review indicates that different electrochemical and optical sensors have been successfully implemented for the detection of fibrinogen under normal levels of fibrinogen in plasma. The biosensors for the detection of fibrinogen have been designed based on the quartz crystal microbalance, field-effect transistor, electrochemical impedance spectroscopy, amperometry, surface plasmon resonance, localized surface plasmon resonance, and colorimetric techniques. Also, this review demonstrates the utility of the application of nanoparticles in different detection techniques.

In Vivo Biocompatibility Study on Functional Nanostructures Containing Bioactive Glass and Plant Extracts for Implantology.

In this paper, the in vivo behavior of orthopedic implants covered with thin films obtained by matrix-assisted pulsed laser evaporation and containing bioactive glass, a polymer, and natural plant extract was evaluated. In vivo testing was performed by carrying out a study on guinea pigs who had coated metallic screws inserted in them and also controls, following the regulations of European laws regarding the use of animals in scientific studies. After 26 weeks from implantation, the guinea pigs were subjected to X-ray analyses to observe the evolution of osteointegration over time; the guinea pigs' blood was collected for the detection of enzymatic activity and to measure values for urea, creatinine, blood glucose, alkaline phosphatase, pancreatic amylase, total protein, and glutamate pyruvate transaminase to see the extent to which the body was affected by the introduction of the implant. Moreover, a histopathological assessment of the following vital organs was carried out: heart, brain, liver, and spleen. We also assessed implanted bone with adjacent tissue. Our studies did not find significant variations in biochemical and histological results compared to the control group or significant adverse effects caused by the implant coating in terms of tissue compatibility, inflammatory reactions, and systemic effects.

Coordinative Compounds Based on Unsaturated Carboxylate with Versatile Biological Applications.

This review presents an overview of the biological applications of coordinative compounds based on unsaturated carboxylates accompanied by other ligands, usually N-based heterocyclic species. The interest in these compounds arises from the valuable antimicrobial and antitumor activities evidenced by some species, as well as from their ability to generate metal-containing polymers suitable for various medical purposes. Therefore, we describe the recently discovered aspects related to the synthesis, structure, and biological activity of a wide range of unsaturated carboxylate-containing species and metal ions, originating mostly from 3d series. The unsaturated carboxylates encountered in coordinative compounds are acrylate, methacrylate, fumarate, maleate, cinnamate, ferulate, coumarate, and itaconate. Regarding the properties of the investigated compounds, it is worth mentioning the good ability of some to inhibit the development of resistant strains or microbial biofilms on inert surfaces or, even more, exert antitumor activity against resistant cells. The ability of some species to intercalate into DNA strands as well as to scavenge ROS species is also addressed.

An Overview of Various Applications of Cadmium Carboxylate Coordination Polymers.

This review highlights the most recent applications of Cd(II)-carboxylate-based coordination polymers (Cd(II)-CBCPs), such as sensors, catalysts, and storage materials, in comparison with those of Zn(II) counterparts. A wide range of species with luminescence properties were designed by using proper organic fluorophores, especially a carboxylate bridging ligand combined with an ancillary N-donor species, both with a rigid structure. These characteristics, combined with the arrangement in Cd(II)-CBCPs' structure and the intermolecular interaction, enable the sensing behavior of a plethora of various inorganic and organic pollutants. In addition, the Lewis acid behavior of Cd(II) was investigated either in developing valuable heterogeneous catalysts in acetalization, cyanosilylation, Henry or Strecker reactions, Knoevenagel condensation, or dyes or drug elimination from wastewater through photocatalysis. Furthermore, the pores structure of such derivatives induced the ability of some species to store gases or toxic dyes. Applications such as in herbicides, antibacterials, and electronic devices are also described together with their ability to generate nano-CdO species.

Copper(II) Methacrylate Complexes with Imidazole Derivatives-Structural, Spectral and Antitumor Features.

A series of five novel copper(II) complexes with imidazole derivatives having general core Cu(R-Im)2(Macr)2 (Macr = methacrylate anion; R-Im = 2-methylimidazole/2-MeIm, 4-methylimidazole/4-MeIm, 2-ethylimidazole/2-EtIm, 2-isopropylimidazole/2-iPrIm) has been synthesized and characterized by elemental analysis, Fourier Transform Infrared spectroscopy (FTIR), electronic reflectance spectroscopy, cyclic voltammetry, thermal analysis and single crystal X-ray diffraction. All complexes crystalize in a monoclinic crystal system and form a complex supramolecular network developed through hydrogen bonds. The stereochemistry of the copper ion is distorted octahedral except for the compound with 4-methylimidazole for which the geometry is square-pyramidal. The imidazole derivatives act as unidentate while methacrylate ions are chelated except for compound with 4-methylimidazole where is unidentate. All ligands and complexes inhibited B16 murine melanoma cells in a micromolar range, but the complex with 2-isopropylimidazole was more active. Furthermore, all species do not affect the healthy BJ cells in the concentration range used for assays.

Decavanadate-Bearing Guanidine Derivatives Developed as Antimicrobial and Antitumor Species.

To obtain biologically active species, a series of decavanadates (Hpbg)4[H2V10O28]·6H2O (1) (Htbg)4[H2V10O28]·6H2O; (2) (Hgnd)2(Hgnu)4[V10O28]; (3) (Hgnu)6[V10O28]·2H2O; and (4) (pbg = 1-phenyl biguanide, tbg = 1-(o-tolyl)biguanide, gnd = guanidine, and gnu = guanylurea) were synthesized and characterized by several spectroscopic techniques (IR, UV-Vis, and EPR) as well as by single crystal X-ray diffraction. Compound (1) crystallizes in space group P-1 while (3) and (4) adopt the same centrosymmetric space group P21/n. The unusual signal identified by EPR spectroscopy was assigned to a charge-transfer π(O)→d(V) process. Both stability in solution and reactivity towards reactive oxygen species (O2- and OH·) were screened through EPR signal modification. All compounds inhibited the development of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis bacterial strains in a planktonic state at a micromolar level, the most active being compound (3). However, the experiments conducted at a minimal inhibitory concentration (MIC) indicated that the compounds do not disrupt the biofilm produced by these bacterial strains. The cytotoxicity assayed against A375 human melanoma cells and BJ human fibroblasts by testing the viability, lactate dehydrogenase, and nitric oxide levels indicated compound (1) as the most active in tumor cells.

Copper (II) Species with Improved Anti-Melanoma and Antibacterial Activity by Inclusion in ß-Cyclodextrin.

To improve their biological activity, complexes [Cu(bipy)(dmtp)2(OH2)](ClO4)2·dmtp (1) and [Cu(phen)(dmtp)2(OH2)](ClO4)2·dmtp (2) (bipy 2,2'-bipyridine, phen: 1,10-phenantroline, and dmtp: 5,7-dimethyl-1,2,4-triazolo [1,5-a]pyrimidine) were included in ß-cyclodextrins (ß-CD). During the inclusion, the co-crystalized dmtp molecule was lost, and UV-Vis spectra together with the docking studies indicated the synthesis of new materials with 1:1 and 1:2 molar ratios between complexes and ß-CD. The association between Cu(II) compounds and ß-CD has been proven by the identification of the components' patterns in the IR spectra and powder XRD diffractograms, while solid-state UV-Vis and EPR spectra analysis highlighted a slight modification of the square-pyramidal stereochemistry around Cu(II) in comparison with precursors. The inclusion species are stable in solution and exhibit the ability to scavenge or trap ROS species (O2·- and HO·) as indicated by the EPR experiments. Moreover, the two inclusion species exhibit anti-proliferative activity against murine melanoma B16 cells, which has been more significant for (2)@ß-CD in comparison with (2). This behavior is associated with a cell cycle arrest in the G0/G1 phase. Compared with precursors, (1a)@ß-CD and (2a)@ß-CD exhibit 17 and 26 times more intense activity against planktonic Escherichia coli, respectively, while (2a)@ß-CD is 3 times more active against the Staphylococcus aureus strain.

An Interesting Conversion Route of Mononuclear Zinc Complex to Zinc Mixed Carboxylate Coordination Polymer.

A complex [Zn(bpy)(acr)2]·H2O (1) was converted in a DMF medium (DMF = N,N'-dimethylformamide) into a coordination polymer [Zn(bpy)(acr)(HCOO)]n (1a) (bpy = 2,2'-bipyridine, and Hacr = acrylic acid), and the species was fully characterized through a single crystal X-ray diffraction. Additional data were obtained by IR and thermogravimetric analysis. Complex (1a) crystalized the coordination polymer in the space group Pca21 of an orthorhombic system. Structural characterization revealed that Zn(II) adopted a square pyramidal stereochemistry generated by bpy molecules, coordinated by chelate, acrylate, and formate ions as unidentate and bridged, respectively. The presence of both the formate and the acrylate with different coordination modes generated two bands in ranges that were characteristic for the carboxylate vibration modes. Thermal decomposition occurs in two complex steps: it first happens via a bpy release, which is followed by an overlapped process that is associated with acrylate and formate decomposition. The obtained complex is of present interest due to the presence of two different carboxylates in its composition and situation, which is rarely reported in the literature.

Zinc(II) Carboxylate Coordination Polymers with Versatile Applications.

This review considers the applications of Zn(II) carboxylate-based coordination polymers (Zn-CBCPs), such as sensors, catalysts, species with potential in infections and cancers treatment, as well as storage and drug-carrier materials. The nature of organic luminophores, especially both the rigid carboxylate and the ancillary N-donor bridging ligand, together with the alignment in Zn-CBCPs and their intermolecular interaction modulate the luminescence properties and allow the sensing of a variety of inorganic and organic pollutants. The ability of Zn(II) to act as a good Lewis acid allowed the involvement of Zn-CBCPs either in dye elimination from wastewater through photocatalysis or in pathogenic microorganism or tumor inhibition. In addition, the pores developed inside of the network provided the possibility for some species to store gaseous or liquid molecules, as well as to deliver some drugs for improved treatment.

DNA-templated electrodeposition of silver nanoparticles for direct and label-free aptasensing of ochratoxin A.

We present in this work, an aptasensing strategy based on the DNA-templated electrodeposition of silver nanoparticles (AgNPs). The homogeneous electro-deposition of AgNPs on screen printed carbon electrode (SPCE) surface was achieved based on a unique aptamer scaffold. This was constructed by immobilizing a DNA aptamer on SPCE by electrochemical oxidation of its amine groups. The electrodeposition of AgNPs was investigated before and after the addition of the aptamer's specific target; the mycotoxin, ochratoxin A (OTA). Electrochemical characterization by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) showed the effect of the scaffold layer on the electrodeposition of AgNPs. The conformational change induced by aptamer after binding its targeted molecule affects AgNPs electrodeposition and the electron transfer thus allowing OTA detection by cyclic voltammetry. The voltammograms showed a good proportionality between the analyte concentration and the current response. The constructed platform allowed the quantitative aptasensing of OTA within the range of (1.56-400 ng/mL) and the detection limit of 0.6 ng/mL. In term of aptasensor applicability, the proposed strategy showed excellent performance in rice samples.

Metal Complexes-A Promising Approach to Target Biofilm Associated Infections.

Microbial biofilms are represented by sessile microbial communities with modified gene expression and phenotype, adhered to a surface and embedded in a matrix of self-produced extracellular polymeric substances (EPS). Microbial biofilms can develop on both prosthetic devices and tissues, generating chronic and persistent infections that cannot be eradicated with classical organic-based antimicrobials, because of their increased tolerance to antimicrobials and the host immune system. Several complexes based mostly on 3D ions have shown promising potential for fighting biofilm-associated infections, due to their large spectrum antimicrobial and anti-biofilm activity. The literature usually reports species containing Mn(II), Ni(II), Co(II), Cu(II) or Zn(II) and a large variety of multidentate ligands with chelating properties such as antibiotics, Schiff bases, biguanides, N-based macrocyclic and fused rings derivatives. This review presents the progress in the development of such species and their anti-biofilm activity, as well as the contribution of biomaterials science to incorporate these complexes in composite platforms for reducing the negative impact of medical biofilms.

Insights into Structure and Biological Activity of Copper(II) and Zinc(II) Complexes with Triazolopyrimidine Ligands.

In an attempt to increase the biological activity of the 1,2,4-triazolo[1,5-a]pyrimidine scaffold through complexation with essential metal ions, the complexes trans-[Cu(mptp)2Cl2] (1), [Zn(mptp)Cl2(DMSO)] (2) (mptp: 5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine), [Cu2(dmtp)4Cl4]·2H2O (3) and [Zn(dmtp)2Cl2] (4) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized as new antiproliferative and antimicrobial species. Both complexes (1) and (2) crystallize in the P21/n monoclinic space group, with the tetrahedral surroundings generating a square-planar stereochemistry in the Cu(II) complex and a tetrahedral stereochemistry in the Zn(II) species. The mononuclear units are interconnected in a supramolecular network through π-π interactions between the pyrimidine moiety and the phenyl ring in (1) while supramolecular chains resulting from C-H∙∙∙π interactions were observed in (2). All complexes exhibit an antiproliferative effect against B16 tumor cells and improved antibacterial and antifungal activities compared to the free ligands. Complex (3) displays the best antimicrobial activity against all four tested strains, both in the planktonic and biofilm-embedded states, which can be correlated to its stronger DNA-binding and nuclease-activity traits.

Antiproliferative and antibacterial properties of biocompatible copper(II) complexes bearing chelating N,N-heterocycle ligands and potential mechanisms of action.

In an attempt to propose new applications for the biomedical field, complexes with mixed ligands {[Cu(bpy)2(µ2OClO3)]ClO4}n (1) and [Cu(phen)2(OH2)](ClO4)2 (2) (bpy: 2,2'-biyridine; phen and 1,10-phenantroline) were evaluated for their antibacterial and cytotoxicicity features and for the elucidation of some of the mechanisms involved. Complex (2) proved to be a very potent antibacterial agent, exhibing MIC and MBEC values 2 to 54 times lower than those obtained for complex (1) against both susceptible or resistant Gram-positive and Gram-negative strains, in planktonic or biofilm growth state. In exchange, complex (1) exhibited selective cytotoxicity against melanoma tumor cells (B16), proving a promising potential for developing novel anticancer drugs. The possible mechanisms of both antimicrobial and antitumor activity of the copper(II) complexes is their DNA intercalative ability coupled with ROS generation. The obtained results recommend the two complexes for further development as multipurpose copper-containing drugs.

Analysis of Recent Bio-/Nanotechnologies for Coronavirus Diagnosis and Therapy.

Despite barrier measures and physical distancing tailored by the populations worldwide, coronavirus continues to spread causing severe health and social-economic problems. Therefore, researchers are focusing on developing efficient detection and therapeutic platforms for SARS-CoV2. In this context, various biotechnologies, based on novel molecules targeting the virus with high specificity and affinity, have been described. In parallel, new approaches exploring nanotechnology have been proposed for enhancing treatments and diagnosis. We discuss in the first part of this review paper, the different biosensing and rapid tests based on antibodies, nucleic acids and peptide probes described since the beginning of the pandemic. Furthermore, given their numerous advantages, the contribution of nanotechnologies is also highlighted.

Wearable Biosensors: An Alternative and Practical Approach in Healthcare and Disease Monitoring.

With the increasing prevalence of growing population, aging and chronic diseases continuously rising healthcare costs, the healthcare system is undergoing a vital transformation from the traditional hospital-centered system to an individual-centered system. Since the 20th century, wearable sensors are becoming widespread in healthcare and biomedical monitoring systems, empowering continuous measurement of critical biomarkers for monitoring of the diseased condition and health, medical diagnostics and evaluation in biological fluids like saliva, blood, and sweat. Over the past few decades, the developments have been focused on electrochemical and optical biosensors, along with advances with the non-invasive monitoring of biomarkers, bacteria and hormones, etc. Wearable devices have evolved gradually with a mix of multiplexed biosensing, microfluidic sampling and transport systems integrated with flexible materials and body attachments for improved wearability and simplicity. These wearables hold promise and are capable of a higher understanding of the correlations between analyte concentrations within the blood or non-invasive biofluids and feedback to the patient, which is significantly important in timely diagnosis, treatment, and control of medical conditions. However, cohort validation studies and performance evaluation of wearable biosensors are needed to underpin their clinical acceptance. In the present review, we discuss the importance, features, types of wearables, challenges and applications of wearable devices for biological fluids for the prevention of diseased conditions and real-time monitoring of human health. Herein, we summarize the various wearable devices that are developed for healthcare monitoring and their future potential has been discussed in detail.

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands.

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2'-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp-both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.

Low Response to Clopidogrel in Coronary Artery Disease.

BACKGROUND: In patients with coronary artery disease, cardiovascular mortality and other acute events showed a clear correlation with risk factors and biomarkers including platelet activation. STUDY QUESTION OF THIS RESEARCH: Which was the incidence of low response to clopidogrel and its correlation with risk factors and biomarkers in coronary artery disease? STUDY DESIGN: Four hundred patients (pts) with coronary artery disease-stable angina (SA) and acute coronary syndrome-were divided into 8 groups of study, consistent with low response to clopidogrel and the type of coronary artery disease. Low response to clopidogrel-defined as adenosine diphosphate test-ADP-test of >46 U by multiple electrode platelet aggregometry was evaluated in correlation with cardiovascular risk factors and biomarkers of oxidative stress, endothelial dysfunction, hypercoagulability, high platelet reactivity. RESULTS: In coronary artery disease, low response to clopidogrel significantly correlated with older than 65 years, smoking, hypertension, diabetes mellitus, body mass index of >25, previous aspirin treatment (P < 0.05), high value of total and low-density lipoprotein cholesterol, low value of high-density lipoprotein cholesterol, low response to aspirin, high mean platelets volume and von Willebrand factor activity, low flow-mediated vasodilatation, total antioxidant status (P < 0.01) and only in patients with SA of male gender (P < 0.01). The incidence of other hypercoagulability biomarkers, such as reduced values of S protein, C protein, antithrombin III, and V Factor Leiden resistance to activated protein C, was very low and not correlated with low response to clopidogrel. CONCLUSIONS: In coronary artery disease, low response to clopidogrel significantly correlated with the most of old cardiovascular risk factors, with previous aspirin treatment, low response to aspirin, higher mean platelets volume, higher von Willebrand factor activity, lower flow-mediated vasodilatation, and lower total antioxidant status values and only in patients with SA of male gender.

Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix.

Every year, more Cu(II) complexes are proven to be biologically active species, but very few are developed as drugs or entered in clinical trials. This is due to their poor water solubility and lipophilicity, low stability as well as in vivo inactivation. The possibility to improve their pharmacological and/or oral administration profile by incorporation into inorganic or organic matrix was studied. Most of them are either physically encapsulated or conjugated to the matrix via a moiety able to coordinate Cu(II). As a result, a large variety of species were developed as delivery carriers. The organic carriers include liposomes, synthetic or natural polymers or dendrimers, while the inorganic ones are based on carbon nanotubes, hydrotalcite and silica. Some hybrid organic-inorganic materials based on alginate-carbonate, gold-PEG and magnetic mesoporous silica-Schiff base were also developed for this purpose.

New Cobalt (II) Complexes with Imidazole Derivatives: Antimicrobial Efficiency against Planktonic and Adherent Microbes and In Vitro Cytotoxicity Features.

Three novel Co(II) complexes of the type [Co(C4H5O2)2L2] (where C4H5O2 is methacrylate anion; L = C3H4N2 (imidazole; HIm) (1), C4H6N2 (2-methylimidazole; 2-MeIm) (2), C5H8N2 (2-ethylimidazole; 2-EtIm) (3)) have been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopic techniques, thermal analysis and single crystal X-ray diffraction. X-ray crystallography revealed for complexes (1) and (2) distorted trigonal bipyramid stereochemistry for Co(II), meanwhile for complex (3) evidenced that the unit cell comprises three molecular units with interesting structural features. In each unit, both stereochemistry adopted by metallic ion and coordination modes of carboxylate anions are different. The screening of antimicrobial activity revealed that Candida albicans planktonic cells were the most susceptible, with minimal inhibitory concentration (MIC) values of 7.8 µg/mL for complexes (1) and (2) and 15.6 µg/mL for complex (3). Complexes (1) and (2) proved to be more active than complex (3) against the tested bacterial strains, both in planktonic and biofilm growth state, with MIC and minimal biofilm eradication concentration (MBEC) values ranging from 15.6 to 62.5 µg/mL, the best antibacterial effects being noticed against Staphylococcus aureus and Pseudomonas aeruginosa. Remarkably, the MBEC values obtained for the four tested bacterial strains were either identical or even lower than the MIC ones. The cytotoxicity assay indicated that the tested complexes affected the cellular cycle of HeLa, HCT-8, and MG63 cells, probably by inhibiting the expression of vimentin and transient receptor potential canonical 1 (TRPC1). The obtained biological results recommend these complexes as potential candidates for the development of novel anti-biofilm agents.

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies.

"Drug repositioning" is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y3+, La3+, Sm3+, Eu3+, Gd3+, Tb3+) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm3+ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (Kb) towards double stranded DNA in the range of 9.33 × 104 - 10.72 × 105. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.