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2.
Cell Death Dis ; 15(6): 419, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879621

ABSTRACT

TRPV6 calcium channel is a prospective target in prostate cancer (PCa) since it is not expressed in healthy prostate while its expression increases during cancer progression. Despite the role of TRPV6 in PCa cell survival and apoptotic resistance has been already established, no reliable tool to target TRPV6 channel in vivo and thus to reduce tumor burden is known to date. Here we report the generation of mouse monoclonal antibody mAb82 raised against extracellular epitope of the pore region of the channel. mAb82 inhibited TRPV6 currents by 90% at 24 µg/ml in a dose-dependent manner while decreasing store-operated calcium entry to 56% at only 2.4 µg/ml. mAb82 decreased PCa survival rate in vitro by 71% at 12 µg/ml via inducing cell death through the apoptosis cascade via activation of the protease calpain, following bax activation, mitochondria enlargement, and loss of cristae, Cyt C release, pro-caspase 9 cleavage with the subsequent activation of caspases 3/7. In vivo, mice bearing either PC3Mtrpv6+/+ or PC3Mtrpv6-/-+pTRPV6 tumors were successfully treated with mAb82 at the dose as low as 100 µg/kg resulting in a significant reduction tumor growth by 31% and 90%, respectively. The survival rate was markedly improved by 3.5 times in mice treated with mAb82 in PC3Mtrpv6+/+ tumor group and completely restored in PC3Mtrpv6-/-+pTRPV6 tumor group. mAb82 showed a TRPV6-expression dependent organ distribution and virtually no toxicity in the same way as mAbAU1, a control antibody of the same Ig2a isotype. Overall, our data demonstrate for the first time the use of an anti-TRPV6 monoclonal antibody in vitro and in vivo in the treatment of the TRPV6-expressing PCa tumors.


Subject(s)
Antibodies, Monoclonal , Apoptosis , Calcium Channels , Prostatic Neoplasms , TRPV Cation Channels , Male , TRPV Cation Channels/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Apoptosis/drug effects , Humans , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Mice , Calcium Channels/metabolism , Cell Line, Tumor , Xenograft Model Antitumor Assays , Calpain/metabolism , Calcium/metabolism
4.
Analyst ; 149(8): 2481-2482, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38506053

ABSTRACT

Correction for 'Diamond nanowires modified with poly[3-(pyrrolyl)carboxylic acid] for the immobilization of histidine-tagged peptides' by Palaniappan Subramanian et al., Analyst, 2014, 139, 4343-4349, https://doi.org/10.1039/C4AN00146J.

6.
ACS Appl Mater Interfaces ; 16(12): 14645-14660, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38478795

ABSTRACT

The greater advantages and wide applications of zero-dimensional nanodots inspire researchers to develop new materials. Therefore, novel borophene quantum dots (QDs) were prepared by a hydrothermal liquid exfoliation technique using water medium. The borophene QDs proved to be highly stable in water medium for more than 120 days. The synthesized borophene QDs revealed intrinsic peroxidase mimetic activity using two chromogenic substrates, 3,3',5,5'-tetramethylbenzidine (TMB) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt (ABTS). The excellent intrinsic peroxidase activity toward TMB and ABTS substrates was executed using optimal reaction conditions (pH, borophene QDs' concentration, incubation time, and temperature). The formation of hydroxyl radicals in the presence of H2O2 upon TMB and ABTS oxidation played a significant role in the peroxidase reaction. The borophene QDs further proved to be successful for the colorimetric detection of antibiotics (oxytetracycline and tetracycline) using both TMB and ABTS peroxidase substrates. The limit of detection (LOD) for oxytetracycline and tetracycline was found to be 1.10 and 1.02 µM using TMB and 1.03 and 1.02 µM using ABTS chromogenic substrates, respectively. In addition, the fluorescence sensing of oxytetracycline and tetracycline over borophene QDs was also examined. The high fluorescence of borophene QDs (turn ON) was quenched (turn OFF) by oxytetracycline and tetracycline through the inner filter effect mechanism. The LOD of the fluorescence sensing of oxytetracycline and tetracycline was 1.14 and 1.08 µM, respectively. Interestingly, the borophene QDs could be used for the sensitive and selective colorimetric and fluorometric sensing of oxytetracycline and tetracycline after 120 days of storage. The synthesized borophene QDs with long-term stability and real sample analysis provide new insight as nanozymes with higher peroxidase mimetic and fluorescence performance and can be further exploited for medical diagnosis and environmental toxicants' detection.


Subject(s)
Benzothiazoles , Oxytetracycline , Quantum Dots , Sulfonic Acids , Peroxidase , Chromogenic Compounds , Hydrogen Peroxide/analysis , Peroxidases , Anti-Bacterial Agents/analysis , Tetracycline , Colorimetry/methods , Water
7.
ACS Pharmacol Transl Sci ; 7(3): 757-770, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38481677

ABSTRACT

Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B.1.351) RBD (KD < 1 pM) and decreasing affinity for the Delta (B.1.617.2) and Omicron (B.1.1.529) variants (86 pM and 19.7 nM, respectively). P2712 potently inhibited the ACE2:RBD interaction, suggesting its utility as a therapeutic. With an IC50 = 0.4 ± 0.1 nM obtained from neutralization experiments using pseudoviral particles, nanoCLAMP P2712 protected K18-hACE2 mice from SARS-CoV-2 infection, reduced viral loads in the lungs and brains, and reduced associated upregulation of inflammatory cytokines and chemokines. Together, our findings warrant further investigation into the development of nanoCLAMPs as effective intranasally delivered COVID-19 therapeutics.

8.
Nanoscale Adv ; 6(6): 1720-1726, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38482034

ABSTRACT

The in situ growth of N-doped multi-walled carbon nanotubes (N-MWCNTs) from the products of graphitic carbon nitride (g-C3N4) etching by Ni nanoparticles in a hydrogen atmosphere has been confirmed for the first time. During the etching process of g-C3N4, the building blocks, notably methane, ammonia, and hydrogen cyanide, are formed. The formation of N-MWCNTs was confirmed by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning (SEM) and transmission electron microscopy (TEM). A sponge-like carbonaceous structure was obtained with a specific surface area of 384 m2 g-1 from initial g-C3N4 (32 m2 g-1).

9.
Adv Healthc Mater ; 13(14): e2303475, 2024 06.
Article in English | MEDLINE | ID: mdl-38310366

ABSTRACT

Deep eutectic solvents (DESs) have been intensively investigated in recent years for their antibacterial properties, with DESs that comprise organic acids (OA-DESs) showing promising antibacterial action. However a majority of the reports focused only on a limited number strains and techniques, which is not enough to determine the antibacterial potential of a substance. To bridge this gap, the antibacterial activity of classical DESs and OA-DESs is assessed on twelve Gram-negative and Gram-positive bacteria strains, with some of them exhibiting specific resistance toward antibiotics. The investigated formulations of OA-DESs comprise glycolic, malic, malonic, and oxalic acids as representatives of this group. Using a range of microbiological assays as well as physicochemical characterization methods, a major difference of the effectiveness between the two groups is demonstrated, with OA-DESs exhibiting, as expected, greater antibacterial effectiveness than classical DESs. Most interestingly, slight differences in the minimum inhibitory and bactericidal concentration values as well as time-kill kinetics profiles are observed between Gram-positive and Gram-negative strains. Transmission electron microscopy analysis reveals the effect of the treatment of the bacteria with the representatives of both groups of DESs, which allows us to better understand the possible mechanism-of-action of these novel materials.


Subject(s)
Anti-Bacterial Agents , Gram-Negative Bacteria , Gram-Positive Bacteria , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Gram-Positive Bacteria/drug effects , Gram-Negative Bacteria/drug effects , Deep Eutectic Solvents/chemistry , Solvents/chemistry
10.
Inorg Chem ; 63(5): 2327-2339, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38270093

ABSTRACT

As a hydrogen carrier and a vital component in fertilizer production, ammonia (NH3) is set to play a crucial role in the planet's future. While its industrial production feeds half of the global population, it uses fossil fuels and emits greenhouse gases. To tackle this issue, photocatalytic nitrogen fixation using visible light is emerging as an effective alternative method. This strategy avoids carbon dioxide (CO2) emissions and harnesses the largest share of sunlight. In this work, we successfully incorporated a 5-nitro isophthalic acid linker into MOF-808 to introduce structural defects and open metal sites. This has allowed modulation of the electronic structure of the MOF and effectively reduced the band gap energy from 3.8 to 2.6 eV. Combination with g-C3N4 enhanced further NH3 production, as these two materials possess similar band gap energies, and g-C3N4 has shown excellent performance for this reaction. The nitro groups serve as acceptors, and their integration into the MOF structure allowed effective interaction with the free electron pairs on N-(C)3 in the g-C3N4 network nodes. Based on DFT calculations, it was concluded that the adsorption of N2 molecules on open metal sites caused a decrease in their triple bond energy. The modified MOF-808 showed superior performance compared with the other MOFs studied in terms of N2 photoreduction under visible light. This design concept offers valuable information about how to engineer band gap energy in MOF structures and their combination with appropriate semiconductors for solar-powered photocatalytic reactions, such as N2 or CO2 photoreduction.

11.
Anal Bioanal Chem ; 416(9): 2137-2150, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37269306

ABSTRACT

Two-dimensional (2D) materials hold great promise for future applications, notably their use as biosensing channels in the field-effect transistor (FET) configuration. On the road to implementing one of the most widely used 2D materials, graphene, in FETs for biosensing, key issues such as operation conditions, sensitivity, selectivity, reportability, and economic viability have to be considered and addressed correctly. As the detection of bioreceptor-analyte binding events using a graphene-based FET (gFET) biosensor transducer is due to either graphene doping and/or electrostatic gating effects with resulting modulation of the electrical transistor characteristics, the gFET configuration as well as the surface ligands to be used have an important influence on the sensor performance. While the use of back-gating still grabs attention among the sensor community, top-gated and liquid-gated versions have started to dominate this area. The latest efforts on gFET designs for the sensing of nucleic acids, proteins and virus particles in different biofluids are presented herewith, highlighting the strategies presently engaged around gFET design and choosing the right bioreceptor for relevant biomarkers.


Subject(s)
Biosensing Techniques , Graphite , Nucleic Acids , Transistors, Electronic , Proteins , Biomarkers , Biosensing Techniques/methods
12.
Anal Bioanal Chem ; 416(9): 2247-2259, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38006442

ABSTRACT

Centralized laboratories in which analytical processes are automated to enable the analysis of large numbers of samples at relatively low cost are used for analytical testing throughout the world. However, healthcare is changing, partly due to the general recognition that care needs to be more patient-centered and putting the patient at the center of action. One way to achieve this goal is to consider point-of-care testing (PoC) devices as alternative analytical concepts. This requires miniaturization of current analytical concepts and the use of cost-effective diagnostic tools with appropriate sensitivity and specificity. Electrochemical sensors are ideally adapted as they provide robust, low-cost, and miniaturized solutions for the detection of variable analytes, yet lack the high sensitivity comparable to more classical diagnosis approaches. Advances in nanotechnology have opened up a plethora of different nanomaterials to be applied as electrode and/or sensing materials in electrochemical biosensors. The choice of materials significantly influences the sensor's sensitivity, selectivity, and overall performance. A critical review of the state of the art with respect to the development of the utilized materials (between 2019 and 2023) and where the field is heading to are the focus of this article.


Subject(s)
Biosensing Techniques , Nanostructures , Humans , Materials Science , Biosensing Techniques/methods , Nanotechnology/methods , Sensitivity and Specificity , Electrochemical Techniques
19.
ACS Appl Mater Interfaces ; 15(50): 58345-58355, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38063412

ABSTRACT

Seawater electrolysis represents a viable alternative for large-scale synthesis of hydrogen (H2), which is recognized as the most promising clean energy source, without relying on scarce fresh water. However, high energy cost and harmful chlorine chemistry in seawater limited its development. Herein, an effective catalyst based on a ruthenium nanoparticle-Ti3C2 MXene composite loaded on nickel foam (RuO2-Ti3C2/NF) with an open, fine, and homogeneous nanostructure was devised and synthesized by electrodeposition for high performance and stable overall seawater splitting. To drive a current density of 100 mA cm-2, the RuO2-Ti3C2/NF electrode required a small overpotential of 85 and 351 mV for HER and OER in 1 M KOH with only a slight increase in 1 M KOH seawater (156 and 378 mV for, respectively, HER and OER). An assembled RuO2-Ti3C2/NF-based two-electrode cell required an overpotential of only 1.84 V to acquire 100 mA cm-2 in 1 M KOH seawater and maintained its activity for over 25 h. This low cell voltage effectively prevented chlorine electrochemical evolution without anode protection. These promising results open up new avenues for the effective conversion of abundant seawater resources to hydrogen fuel.

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