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Journal of Colloid and Interface Science Jun 2024Bacteria-associated infections and thrombus formation are the two major complications plaguing the application of blood-contacting medical devices. Therefore,...
Bacteria-associated infections and thrombus formation are the two major complications plaguing the application of blood-contacting medical devices. Therefore, functionalized surfaces and drug delivery for passive and active antifouling strategies have been employed. Herein, we report the novel integration of bio-inspired superhydrophobicity with nitric oxide release to obtain a functional polymeric material with anti-thrombogenic and antimicrobial characteristics. The nitric oxide release acts as an antimicrobial agent and platelet inhibitor, while the superhydrophobic components prevent non-specific biofouling. Widely used medical-grade silicone rubber (SR) substrates that are known to be susceptible to biofilm and thrombus formation were dip-coated with fluorinated silicon dioxide (SiO) and silver (Ag) nanoparticles (NPs) using an adhesive polymer as a binder. Thereafter, the resulting superhydrophobic (SH) SR substrates were impregnated with S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) to obtain a superhydrophobic, Ag-bound, NO-releasing (SH-SiAgNO) surface. The SH-SiAgNO surfaces had the lowest amount of viable adhered E. coli (> 99.9 % reduction), S. aureus (> 99.8 % reduction), and platelets (> 96.1 % reduction) as compared to controls while demonstrating no cytotoxic effects on fibroblast cells. Thus, this innovative approach is the first to combine SNAP with an antifouling SH polymer surface that possesses the immense potential to minimize medical device-associated complications without using conventional systemic anticoagulation and antibiotic treatments.
Topics: Humans; Nitric Oxide; Silver; S-Nitroso-N-Acetylpenicillamine; Staphylococcus aureus; Escherichia coli; Silicon Dioxide; Anti-Bacterial Agents; Anti-Infective Agents; Hydrophobic and Hydrophilic Interactions; Thrombosis; Polymers
PubMed: 38503078
DOI: 10.1016/j.jcis.2024.03.082 -
Proceedings of the National Academy of... Mar 2024The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics....
The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad-spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. penicillamine-stabilized NPs with left-handed curved apexes display half-maximal inhibitory concentrations (IC) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments.
Topics: Humans; Animals; Mice; SARS-CoV-2; COVID-19; Coronavirus OC43, Human; Antibodies; Antiviral Agents
PubMed: 38502692
DOI: 10.1073/pnas.2310469121 -
Tremor and Other Hyperkinetic Movements... 2024The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications.
BACKGROUND
The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications.
PHENOMENOLOGY SHOWN
This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment.
EDUCATIONAL VALUE
This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings.
HIGHLIGHTS
This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.
Topics: Humans; Copper; Hepatolenticular Degeneration; Magnetic Resonance Imaging; Penicillamine; Tremor
PubMed: 38464913
DOI: 10.5334/tohm.857 -
Orphanet Journal of Rare Diseases Mar 2024This study aimed to assess medication adherence and demographic, clinical, and psychopathological parameters such as quality of life, depression, and anxiety levels that...
BACKGROUND
This study aimed to assess medication adherence and demographic, clinical, and psychopathological parameters such as quality of life, depression, and anxiety levels that can affect pediatrics with Wilson's Disease (WD).
METHODS
A prospective cohort study was conducted at an outpatient clinic in Turkey among pediatric patients (2 to 18 years) with WD between November 2022 and April 2023. The Medication Adherence Report Scale (MARS-5) as a subjective and Medication Possession Ratio (MPR) as an objective assessment were scored. Physical, genetic and biochemical parameters, the Pediatric Quality of Life Inventory (PedsQL) for both parents and patients, Childhood Depression Inventory, State Trait Anxiety Inventory were also administered.
RESULTS
A total of 30 pediatric outpatients who were prescribed D-penicillamine (n = 27) or trientine (n = 3) as chelators and zinc (n = 29) and pyridoxine (n = 19) as supplements were included. Proteinuria (n = 3), skin rash (n = 2), and gastrointestinal upset (n = 2) were observed. When the correlation between MARS-5 and duration of follow-up was examined, a significant negative correlation was found (p = 0.014). According to MPRs, non-adherence rates (missed doses ≥ 20%) were 29.6%, 17.2% and 5.3% for D-penicillamine, zinc and pyridoxine, respectively. PedsQL scores were higher than those of parents, with a positive correlation between them (p < 0.001). Also, there was a significant positive correlation between PedsQL and State Anxiety Inventory (p < 0.001). Comparing the change in urinary copper levels between different levels of treatment knowledge, significant differences were observed between high- and low levels (p = 0.043).
CONCLUSIONS
Overall, nonadherence rates were 23.3% based on MARS-5 and 5.3-29.6% based on MPR. It is essential to consider factors such as the duration of follow-up, biochemical parameters, treatment knowledge, quality of life and anxiety as potential influencers of medication adherence.
Topics: Adolescent; Child; Humans; Cohort Studies; Hepatolenticular Degeneration; Penicillamine; Prospective Studies; Pyridoxine; Quality of Life; Turkey; Zinc; Child, Preschool
PubMed: 38454433
DOI: 10.1186/s13023-024-03113-0 -
Journal of Cardiovascular Pharmacology Feb 2024We previously reported a novel compound called S-nitroso-N-pivaloyl-D-penicillamine (SNPiP), which was screened from a group of nitric oxide (NO) donor compounds with a...
Transcriptome Analysis Reveals Enhancement of Cardiogenesis-Related Signaling Pathways by S-nitroso-N-pivaloyl-D-penicillamine (SNPiP): Implications for Improved Diastolic Function and Cardiac Performance.
We previously reported a novel compound called S-nitroso-N-pivaloyl-D-penicillamine (SNPiP), which was screened from a group of nitric oxide (NO) donor compounds with a basic chemical structure of S-nitroso-N-acetylpenicillamine (SNAP), to activate the non-neuronal acetylcholine (NNA) system. SNPiP-treated mice exhibited improved cardiac output and enhanced diastolic function, without an increase in heart rate. The NNA-activating effects included increased resilience to ischemia, modulation of energy metabolism preference, and activation of angiogenesis. Here, we performed transcriptome analysis of SNPiP-treated mice ventricles to elucidate how SNPiP exerts beneficial effects on cardiac function. A time-course study (24 and 48 h after SNPiP administration) revealed that SNPiP initially induced Wnt and cGMP-protein kinase G (PKG) signaling pathways, along with upregulation of genes involved in cardiac muscle tissue development and oxytocin signaling pathway. We also observed enrichment of glycolysis-related genes in response to SNPiP treatment, resulting in a metabolic shift from oxidative phosphorylation to glycolysis, which was suggested by reduced cardiac glucose contents while maintaining ATP levels. Additionally, SNPiP significantly upregulated atrial natriuretic peptide (ANP) and sarcolipin (SLN), which play crucial roles in calcium handling and cardiac performance. These findings suggest that SNPiP may have therapeutic potential based on the pleiotropic mechanisms elucidated in this study.
PubMed: 38422186
DOI: 10.1097/FJC.0000000000001552 -
Chemistry (Weinheim An Der Bergstrasse,... Apr 2024Cu-thiosemicarbazones have been intensively investigated for their application in cancer therapy or as antimicrobials....
Cu-thiosemicarbazones have been intensively investigated for their application in cancer therapy or as antimicrobials. Copper(II)-di-2-pyridylketone-4,4-dimethyl-thiosemicarbazone (Cu-Dp44mT) showed anticancer activity in the submicromolar concentration range in cell culture. The interaction of Cu-Dp44mT with thiols leading to their depletion or inhibition was proposed to be involved in this activity. Indeed, Cu-Dp44mT can catalyze the oxidation of thiols although with slow kinetics. The present work aims to obtain insights into the catalytic activity and selectivity of Cu-Dp44mT toward the oxidation of different biologically relevant thiols. Reduced glutathione (GSH), L-cysteine (Cys), N-acetylcysteine (NAC), D-penicillamine (D-Pen), and the two model proteins glutaredoxin (Grx) and thioredoxin (Trx) were investigated. Cu-Dp44mT catalyzed the oxidation of these thiols with different kinetics, with rates in the following order D-Pen>Cys≫NAC>GSH and Trx>Grx. Cu-Dp44mT was more efficient than Cu chloride for the oxidation of NAC and GSH, but not D-Pen and Cys. In mixtures of biologically relevant concentrations of GSH and either Cys, Trx, or Grx, the oxidation kinetics and spectral properties were similar to that of GSH alone, indicating that the interaction of these thiols with Cu-Dp44mT is dominated by GSH. Hence GSH could protect other thiols against potential deleterious oxidation by Cu-Dp44mT.
Topics: Copper; Sulfhydryl Compounds; Oxidation-Reduction; Thiosemicarbazones; Glutathione; Penicillamine; Acetylcysteine
PubMed: 38408264
DOI: 10.1002/chem.202304212 -
Micromachines Jan 2024D-penicillamine (D-PA) is a sulfur-containing drug that has been used for various health conditions. However, like any medication, overdosing on D-PA can have adverse...
D-penicillamine (D-PA) is a sulfur-containing drug that has been used for various health conditions. However, like any medication, overdosing on D-PA can have adverse effects and may require additional treatment. Therefore, developing simple and sensitive methods for sensing D-PA can play a crucial role in improving its efficacy and reducing its side effects. Sensing technologies, such as electrochemical sensors, can enable accurate and real-time measurement of D-PA concentrations. In this work, we developed a novel electrochemical sensor for detecting D-PA by modifying a carbon paste electrode (CPE) with a multi-walled carbon nanotube-CoO nanocomposite, benzoyl-ferrocene (BF), and ionic liquid (IL) (MWCNT-CoO/BF/ILCPE). Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry (CHA) were employed to explore the electrochemical response of D-PA on the developed sensor, the results of which verified a commendable electrochemical performance towards D-PA. Under optimized conditions, the developed sensor demonstrated a rapid response to D-PA with a linear dynamic range of 0.05 μM-100.0 μM, a low detection limit of 0.015 μM, and a considerable sensitivity of 0.179 μA μM. Also, the repeatability, stability, and reproducibility of the MWCNT-CoO/BF/ILCPE sensor were studied and showed good characteristics. In addition, the detection of D-PA in pharmaceutical and biological matrices yielded satisfactory recoveries and relative standard deviation (RSD) values.
PubMed: 38398949
DOI: 10.3390/mi15020220 -
Biomedical Materials (Bristol, England) Mar 2024Nanoscale materials have demonstrated a very high potential in anticancer therapy by properly adjusting their functionalization and physicochemical properties. Herein,...
Nanoscale materials have demonstrated a very high potential in anticancer therapy by properly adjusting their functionalization and physicochemical properties. Herein, we report the synthesis of some novel vanadocene-loaded silica-based nanomaterials incorporating four different S-containing amino acids (penicillamine, methionine, captopril, and cysteine) and different fluorophores (rhodamine B, coumarin 343 or Alexa Fluor™ 647), which have been characterized by diverse solid-state spectroscopic techniques viz; FTIR, diffuse reflectance spectroscopies,C andV solid-state NMR spectroscopy, thermogravimetry and TEM. The analysis of the biological activity of the novel vanadocene-based nanostructured silicas showed that the materials containing cysteine and captopril aminoacids demonstrated high cytotoxicity and selectivity against triple negative breast cancer cells, making them very promising antineoplastic drug candidates. According to the biological results it seems that vanadium activity is connected to its incorporation through the amino acid, resulting in synergy that increases the cytotoxic activity against cancer cells of the studied materials presumably by increasing cell internalization. The results presented herein hold significant potential for future developments in mesoporous silica-supported metallodrugs, which exhibit strong cytotoxicity while maintaining low metal loading. They also show potential for theranostic applications highlighted by the analysis of the optical properties of the studied systems after incorporating rhodamine B, coumarin 343 (possible)anticancer analysis, or Alexa Fluor™ 647 (studies of cancer models).
Topics: Humans; Female; Breast Neoplasms; Silicon Dioxide; Cysteine; Precision Medicine; Captopril; Nanoparticles; Antineoplastic Agents; Porosity
PubMed: 38387062
DOI: 10.1088/1748-605X/ad2c1c -
Journal of Nanobiotechnology Feb 2024The formation of blood vessel system under a relatively higher Cu ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in...
The formation of blood vessel system under a relatively higher Cu ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.
Topics: Humans; Phototherapy; Copper; Fluorescence; Hyperthermia, Induced; Neoplasms; Ions; Cell Line, Tumor; Nanoparticles; Tumor Microenvironment
PubMed: 38374027
DOI: 10.1186/s12951-024-02343-5 -
Journal of Biomedical Materials... Feb 2024Urinary tract infections (UTIs) are some of the most common infections seen in humans, affecting over half of the female population. Though easily and quickly treatable,...
Urinary tract infections (UTIs) are some of the most common infections seen in humans, affecting over half of the female population. Though easily and quickly treatable, if gone untreated for too long, UTIs can lead to narrowing of the urethra as well as bladder and kidney infections. Due to the disease potential, it is crucial to mitigate the development of UTIs throughout healthcare. Unfortunately, sexual activity and the use of condoms have been identified as common risk factors for the development of sexually acquired UTIs. Therefore, this study outlines a potential alteration to existing condom technology to decrease the risk of developing sexually acquired UTIs using S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor. Herein, varying concentrations of SNAP are integrated into commercialized condoms through a facile solvent swelling method. Physical characterization studies showed that 72%-100% of the ultimate tensile strength was maintained with lower SNAP concentrations, validating the modified condom's mechanical integrity. Additionally, the evaluation of room-temperature storage stability via NO release analysis outlined a lack of special storage conditions needed compared to commercial products. Moreover, these samples exhibited >90% relative cell viability and >96% bacterial killing, proving biocompatibility and antimicrobial properties. SNAP-Latex maintains the desired condom durability while demonstrating excellent potential as an effective new contraceptive technology to mitigate the occurrence of sexually acquired UTIs.
Topics: Humans; Female; Latex; S-Nitroso-N-Acetylpenicillamine; Contraception, Barrier; Condoms; Nitric Oxide Donors; Urinary Tract Infections
PubMed: 38359176
DOI: 10.1002/jbm.b.35371