Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes.

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to a range of neurological symptoms. Despite the heterogeneity of these conditions, a common denominator is the implication of mitochondrial dysfunction in their pathogenesis. Mitochondria play a crucial role in creating biomolecules, providing energy through adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS), and producing reactive oxygen species (ROS).

Current progress, strategy, and prospects of PD-1/PDL-1 immune checkpoint biosensing platforms for cancer diagnostics, therapy monitoring, and drug screening.

Recent technological advancements in testing and monitoring instrumentation have greatly contributed to the progress in cancer treatment by surgical, chemotherapeutic and radiotherapeutic interventions. However, the mortality rate still remains high, calling for the development of new treatment strategies with higher efficacy. Extensive efforts driven in this direction have included broadening of early cancer screening and applying innovative theranostic nanotechnologies.

Effects of Supplementation with an Herbal Mixture on the Antioxidant Capacity of Milk.

The aim of this study was to assess the effect of the addition of a standardized herbal mixture to the feed ration for Holstein-Friesian cows on the antioxidant capacity of milk. The study was carried out on a farm specialized in breeding dairy cattle. The exact study involved 30 cows in lactation III, which were in the first phase of lactation at the beginning of the experiment (15 cows-control group; 15 cows-experimental group).

DNA Aptamer Beacon Probe (ABP) for Monitoring of Adenosine Triphosphate Level in SW480 Cancer Cells Treated with Glycolysis Inhibitor 2-Deoxyglucose.

Early cancer screening enables timely detection of carcinogenesis, and aids in prompt clinical intervention. Herein, we report on the development of a simple, sensitive, and rapid fluorometric assay based on the aptamer probe (aptamer beacon probe, ABP) for monitoring the energy-demand biomarker adenosine triphosphate (ATP), an essential energy source that is released into the tumor microenvironment. Its level plays a significant role in risk assessment of malignancies.

Effective Optical Image Assessment of Cellulose Paper Immunostrips for Blood Typing.

Novel high-performance biosensing devices, based on a microporous cellulose matrix, have been of great interest due to their high sensitivity, low cost, and simple operation. Herein, we report on the design and testing of portable paper-based immunostrips (IMS) for in-field blood typing in emergencies requiring blood transfusion. Cellulose fibrils of a paper membrane were functionalized with antibodies via supramolecular interactions.

Antioxidant Activity of Milk and Dairy Products.

The aim of the study was to present a review of literature data on the antioxidant potential of raw milk and dairy products (milk, fermented products, and cheese) and the possibility to modify its level at the milk production and processing stage. Based on the available reports, it can be concluded that the consumption of products that are a rich source of bioactive components improves the antioxidant status of the organism and reduces the risk of development of many civilization diseases. Milk and dairy products are undoubtedly rich sources of antioxidant compounds.

Organic versus Conventional Raw Cow Milk as Material for Processing.

Milk, as one of the basic raw materials of animal origin, must be of adequate hygienic and physicochemical quality for processing. The aim of the article was to compare the quality of raw milk from three production systems, intensive, traditional (together referred to as conventional), and organic, as material for processing, as well as the quality of products made from it. Particular attention was focused on hygienic quality (somatic cell count and total bacterial count), physical characteristics (acidity), basic nutritional value (content of dry matter, total protein, casein, fat, and lactose), content of health-promoting substances (whey proteins, fatty acids, vitamins, and minerals), and technological parameters (rennet clotting time, heat stability, and protein-to-fat ratio).

Gated Resonance Energy Transfer (gRET) Controlled by Programmed Death Protein Ligand 1.

The resonance energy transfer (RET) between an excited fluorescent probe molecule and a plasmonic nanoparticle (AuNP) has been investigated to evaluate the effect of protein molecules on the RET efficiency. We have found that the energy transfer to a functionalized AuNP can be modulated by a sub-monolayer film of programmed death-ligand 1 (PD-L1) protein. The interactions of PD-L1 with AuNP@Cit involve incorporation of the protein in AuNP shell and formation of a submonolayer adsorption film with voids enabling gated surface plasmon resonance energy transfer (SPRET).

High-performance modified cellulose paper-based biosensors for medical diagnostics and early cancer screening: A concise review.

A remarkable progress in the development of portable paper-based biosensors (PBBs) and microfluidic paper-based analytical devices (μPADs) has recently been achieved. In these devices, a paper formed of microfibers of cellulose, a carbohydrate biopolymer, offers both an ample space in its micropores for analytical reagents storage and a capillary force to drive liquid samples to a dedicated reaction zone for instantaneous detection of the desired analytes. Owing to the low cost and ultra-high sensitivity, these novel devices have become a promising alternative to traditional advanced analytical instruments and offer great potential for applications in medical emergencies, health diagnostics at points-of-care, and broad early-cancer screening.

Monitoring of dynamic ATP level changes by oligomycin-modulated ATP synthase inhibition in SW480 cancer cells using fluorescent "On-Off" switching DNA aptamer.

Adenosine triphosphate (ATP) is the main energy source in cells and an important biomolecule participating in cellular reactions in living organisms. Since the ATP level changes dynamically reflecting the development of a debilitating disease or carcinogenesis, we have focused in this work on monitoring of the oligomycin (OMC)-modulated ATP synthase inhibition using a fluorescent-switching DNA aptamer designed for the detection of ATP (Apt(ATP)), as the model for studies of dynamic ATP level variation. The behavior of the ATP aptamer has been characterized using fluorescence spectroscopy.

Toward early cancer detection: Focus on biosensing systems and biosensors for an anti-apoptotic protein survivin and survivin mRNA.

The development of biosensors for cancer biomarkers has recently been expanding rapidly, offering promising biomedical applications of these sensors as highly sensitive, selective, and inexpensive bioanalytical tools that can provide alternative methodology to that afforded by the advanced hyphenated-instrumental techniques. In this review, we focus particularly on the detection of a member of the inhibitor of apoptosis proteins (IAP) family, protein survivin (Sur), a ubiquitous re-organizer of the cell life cycle with the ability to inhibit the apoptosis and induce an enhanced proliferation leading to the unimpeded cancer growth and metastasis. Herein, we critically evaluate the progress in the development of novel biosensing systems and biosensors for the detection of two survivin (Sur) biomarkers: the Sur protein and its messenger RNA (Sur mRNA), including immunosensors, electrochemical piezo- and impedance-sensors, electrochemi-luminescence biosensors, genosensors based on oligonucleotide molecular beacons (MBs) with fluorescent or electrochemical transduction, as well as the microfluidic and related analytical platforms based on solution chemistry.

New ISE-Based Apparatus for Na, K, Cl, pH and Transepithelial Potential Difference Real-Time Simultaneous Measurements of Ion Transport across Epithelial Cells Monolayer⁻Advantages and Pitfalls.

Cystic Fibrosis (CF) is the most common fatal human genetic disease, which is caused by a defect in an anion channel protein (CFTR) that affects ion and water transport across the epithelium. We devised an apparatus to enable the measurement of concentration changes of sodium, potassium, chloride, pH, and transepithelial potential difference by means of ion-selective electrodes that were placed on both sides of a 16HBE14σ human bronchial epithelial cell line that was grown on a porous support. Using flat miniaturized ISE electrodes allows for reducing the medium volume adjacent to cells to approximately 20 μL and detecting changes in ion concentrations that are caused by transport through the cell layer.

Optical Biosensing System for the Detection of Survivin mRNA in Colorectal Cancer Cells Using a Graphene Oxide Carrier-Bound Oligonucleotide Molecular Beacon.

The anti-apoptotic protein survivin is one of the most promising cancer biomarkers owing to its high expression in human cancers and rare occurrence in normal adult tissues. In this work, we have investigated the role of supramolecular interactions between a graphene oxide (GO) nanosheet nanocarrier and a survivin molecular beacon (SurMB), functionalized by attaching fluorophore Joe and quencher Dabcyl (SurMB-Joe). Molecular dynamics simulations revealed hydrogen bonding of Joe moiety and Dabcyl to GO carriers that considerably increase the SurMB-GO bonding strength.

Hairpin-Hairpin Molecular Beacon Interactions for Detection of Survivin mRNA in Malignant SW480 Cells.

Cancer biomarkers offer unique prospects for the development of cancer diagnostics and therapy. One of such biomarkers, protein survivin (Sur), exhibits strong antiapoptotic and proliferation-enhancing properties and is heavily expressed in multiple cancers. Thus, it can be utilized to provide new modalities for modulating the cell-growth rate, essential for effective cancer treatment.

Supramolecular interactions of oxidative stress biomarker glutathione with fluorone black.

Oxidative stress biomarkers, including glutathione (GSH) and related compounds, are involved in a variety of interactions enabling redox potential maintenance in living cells and protection against radicals. Since the oxidative stress is promoting and, in many cases, inducing serious illnesses, monitoring of GSH levels can aid in diagnostics and disease prevention. Herein, we report on the discovery of the formation of a supramolecular ensemble of GSH with fluorone black (9-phenyl fluorone, FB) which is optically active and enables sensitive determination of GSH by resonance elastic light scattering (RELS).

Ternary Interactions and Energy Transfer between Fluorescein Isothiocyanate, Adenosine Triphosphate, and Graphene Oxide Nanocarriers.

The interactions of fluorescent probes and biomolecules with nanocarriers are of key importance to the emerging targeted drug delivery systems. Graphene oxide nanosheets (GONs) as the nanocarriers offer biocompatibility and robust drug binding capacity. The interactions of GONs with fluorophores lead to strong fluorescence quenching, which may interfere with fluorescence bioimaging and biodetection.

Mitochondria-based biosensors with piezometric and RELS transduction for potassium uptake and release investigations.

Dysfunctional mitochondria appear to be involved in many diseases through their role in respiration, reactive oxygen species generation, and energy production. To aid in the design of new biosensors based on mitochondria (MT), we have investigated the feasibility of detecting ion fluxes through the MT-membrane K-ion channels using piezosensors with MTs immobilized either by hydrogen bonding or thin polypyrrole (PPy) binding film. We have demonstrated for the first time that the mitochondria-based piezosensors are able to detect ion fluxes and thus be utilized for drug development aimed at ion channel opener- or inhibitor-function.

DNA Strand Replacement Mechanism in Molecular Beacons Encoded for the Detection of Cancer Biomarkers.

Signaling properties of a fluorescent hairpin oligonucleotide molecular beacon (MB) encoded to recognize protein survivin (Sur) mRNA have been investigated. The process of complementary target binding to SurMB with 20-mer loop sequence is spontaneous, as expected, and characterized by a high affinity constant (K = 2.51 × 10(16) M(-1)).

Piezometric biosensors for anti-apoptotic protein survivin based on buried positive-potential barrier and immobilized monoclonal antibodies.

The anti-apoptotic protein survivin (Sur) plays an important role in the regulation of cell division and inducing the chemotherapeutic drug resistance. The Sur protein and its mRNA have recently been studied as cancer biomarkers and potential targets for cancer therapy. In this work, we have focused on the design of immunosensors for the detection of Sur based on buried positive-potential barrier layer structure and anti-survivin antibody.

Modulation of Plasmon-Enhanced Resonance Energy Transfer to Gold Nanoparticles by Protein Survivin Channeled-Shell Gating.

The resonance energy transfer (RET) from excited fluorescent probe molecules to plasmonic gold nanoparticles (AuNPs) can be gated by modulating the width of channels (gates) in submonolayer protein shells surrounding AuNPs. We have explored the gated-RET (gRET) processes using an antiapoptotic protein survivin (Sur) as the gating material, citrate-capped gold nanoparticles (AuNP@Cit), and fluorescein isothiocyanate as the fluorescent probe. Despite the electrostatic repulsive forces between these components, a strong modulation of RET efficiency by Sur down to 240 pM (S/N = 3) is possible.

Novel plasmonic field-enhanced nanoassay for trace detection of proteins.

Recently discovered effects of plasmonic field on molecular fluorescence offer new insights into the optical interactions at the nanoscale which can help solving problems encountered in widely applied fluorescent labeling of biomolecules for studying life processes in biomedicine and pharmacy. In this work, we have focused on exploring a novel sensitivity-enhancing phenomenon based on protein modulation of plasmon-controlled fluorescence. We have demonstrated that a protein (cytochrome c (Cytc c) or bovine serum albumin (BSA)) can be employed to gate fluorescence resonance energy transfer occurring from a fluorescein isothiocyanate fluorescent dye to plasmonic citrate-capped gold nanoparticles.

Intervention of glutathione in pre-mutagenic catechol-mediated DNA damage in the presence of copper(II) ions.

The catechol-mediated DNA damage in the presence of Cu(II) ions involves oxidation of guanine to 8-oxoguanine (8-oxoG) and DNA strand scission. It proceeds through the reactive oxygen species (ROS) generation. The mutagenicity of 8-oxoG lesions is due to its miscoding propensity reflected in GC→TA transversion taking place during the DNA repair process.

Mercury/homocysteine ligation-induced ON/OFF-switching of a T-T mismatch-based oligonucleotide molecular beacon.

A molecular beacon (MB) with stem-loop (hairpin) DNA structure and with attached fluorophore-quencher pair at the ends of the strand has been applied to study the interactions of Hg(2+) ions with a thymine-thymine (T-T) mismatch in Watson-Crick base-pairs and the ligative disassembly of MB·Hg(2+) complex by Hg(2+) sequestration with small biomolecule ligands. In this work, a five base-pair stem with configuration 5'-GGTGG..

Effect of buried potential barrier in label-less electrochemical immunodetection of glutathione and glutathione-capped gold nanoparticles.

The influence of potential barriers, introduced to the immunoglobulin-based sensory films, on voltammetric signals of a redox ion probe has been investigated. Films with positive and negative barriers have been examined by depositing charged self-assembled thiol monolayers as the basal layers of a sensory film. The studies performed with monoclonal anti-glutathione antibody-based sensors using ferricyanide ion probe have shown stronger sensor response to the layer components, as well as to the glutathione-capped gold nanoparticles acting as the antigen, for films with positive potential barrier buried deep in the film than for negative barrier films.

Double-shell gold nanoparticle-based DNA-carriers with poly-L-lysine binding surface.

In view of the prospective applications of polyamine coatings in functional gold nanoparticles for use as carriers in gene delivery systems, in tissue repair and as bactericidal and virucidal non-toxic vehicle, we have investigated the interactions of poly-l-lysine (PLL) with gold nanoparticles (AuNP). Since direct binding of PLL to AuNP is not strong at neutral pH, we have focused on PLL interactions with carboxylated self-assembled monolayers (SAM) on AuNP, such as the citrate-capped AuNP. The double-shell nanoparticles AuNP@Cit/PLL thus produced do not contain any toxic thiols.