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Small (Weinheim An Der Bergstrasse,... Mar 2024InP/ZnS quantum dots (QDs) have received a large focus in recent years as a safer alternative to heavy metal-based QDs. Given their intrinsic fluorescent imaging...
InP/ZnS quantum dots (QDs) have received a large focus in recent years as a safer alternative to heavy metal-based QDs. Given their intrinsic fluorescent imaging capabilities, these QDs can be potentially relevant for in vivo platelet imaging. The InP/ZnS QDs are synthesized and their biocompatibility investigated through the use of different phase transfer agents. Analysis of platelet function indicates that platelet-QD interaction can occur at all concentrations and for all QD permutations tested. However, as the QD concentration increases, platelet aggregation is induced by QDs alone independent of natural platelet agonists. This study helps to define a range of concentrations and coatings (thioglycolic acid and penicillamine) that are biocompatible with platelet function. With this information, the platelet-QD interaction can be identified using multiple methods. Fluorescent lifetime imaging microscopy (FLIM) and confocal studies have shown QDs localize on the surface of the platelet toward the center while showing evidence of energy transfer within the QD population. It is believed that these findings are an important stepping point for the development of fluorescent probes for platelet imaging.
Topics: Quantum Dots; Ligands
PubMed: 37946631
DOI: 10.1002/smll.202304881 -
The Journal of Physical Chemistry... Nov 2023Despite significant advances in atomically precise Au clusters with chirality, Ag clusters with the relevant features are still less explored. In this study, we report...
Despite significant advances in atomically precise Au clusters with chirality, Ag clusters with the relevant features are still less explored. In this study, we report successful synthesis of chiral Ag clusters protected by water-soluble in one pot, which is carried out by reducing Ag ions in the presence of -acetyl-()-penicillamine (-NAP) and triphenylphosphine (TPP) at 10 °C, yielding the Ag(-NAP) cluster. The obtained cluster is isolable as a solid-state powder. Optical absorption of Ag(-NAP) is almost identical with that of Ag(-DHLA), where DHLA denotes α-dihydrolipoic acid, and magnetic circular dichroism (MCD) results support the similarity of their electronic structures. The anisotropy factor of Ag(-NAP) is comparable to or larger than that of Ag(-DHLA), suggesting that the surface shell structure of Ag(-NAP) is inherently chiral, as has been observed for Ag(-DHLA). Then the use of enantiopure NAP would preferentially lead to a one-handed atomic arrangement in the clusters.
PubMed: 37942989
DOI: 10.1021/acs.jpclett.3c02780 -
The Veterinary Record Feb 2024Copper-associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS).
BACKGROUND
Copper-associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS).
METHODS
Hepatic copper accumulation was qualitatively and quantitatively assessed, and blood samples were used for genetic testing to screen for known CuCH-associated genetic variants.
RESULTS
The study included 13 CKCS with CuCH and eight unaffected controls. Increased transaminase activities, elevated biliary enzyme concentrations and portal hypertension were documented in 100%, 73% and 38% of dogs with CuCH, respectively. Five dogs had three or more abnormalities in measures of liver function. All 11 dogs with CuCh that underwent genetic testing were homozygous negative for the COMMD1 deletion and ATP7A variant but homozygous positive (n = 7) or heterozygous (n = 4) for the ATP7B variant. Liver histology often demonstrated marked architectural distortion by severe, bridging fibrosis and regenerative nodules with lymphoplasmacytic inflammation. Centrilobular copper accumulation characterised early cases with minimal fibrosis. When fibrosis was significant, copper was often differentially concentrated within regenerative nodules. Chelation therapy resolved laboratory derangements and portal hypertension in five of seven dogs. Of the 7 non-surviving dogs with CuCH, 6 had not received chelation therapy.
LIMITATIONS
Limitations include a small cohort size and the lack of pedigree analyses to corroborate heritability.
CONCLUSIONS
CuCH should be considered in CKCS with suspected liver disease. Long-term prognosis seems favourable in dogs receiving chelation therapy, notwithstanding the presence of previously reported negative prognostic markers.
Topics: Humans; Dogs; Animals; Copper; Fibrosis; Hepatitis, Chronic; Hypertension, Portal; Dog Diseases
PubMed: 37926771
DOI: 10.1002/vetr.3561 -
Journal of Biomolecular Structure &... Nov 2023BCL2, an antiapoptotic protein, is overexpressed in many cancers, making it a good cancer treatment target. In 30 years, few BCL2 targeting agents have shown clinical...
BCL2, an antiapoptotic protein, is overexpressed in many cancers, making it a good cancer treatment target. In 30 years, few BCL2 targeting agents have shown clinical significance. This work designed new amide thiazolidine derived from isoniazid targeting BCL2 and tested them on cancer cell lines, for binding affinities, the novel candidates were docked to the BCL2 target receptor. IC50 of compound A8 46.67 ± 0.9 and 57.14 ± 0.88 μg/ml against PC3 and HEPG2 respectively with docking score -7.6 Kcal/mol with 6GL8 make it the best compound in this series. Melting point, FT-IR, elemental microanalysis (CHN), HNMR, and CNMR confirmed chemical structures.Communicated by Ramaswamy H. Sarma.
PubMed: 37922154
DOI: 10.1080/07391102.2023.2276313 -
ACS Nano Nov 2023Nitric oxide (NO) is a promising approach for treating ocular hypertension and glaucoma. However, its clinical application is limited by its uncontrollable release and...
Nitric oxide (NO) is a promising approach for treating ocular hypertension and glaucoma. However, its clinical application is limited by its uncontrollable release and the unwanted overproduction of peroxynitrite. Herein, a denitrifying hollow mesoporous organosilica nanoparticle (HMMN) with framework cohybridization is first constructed to encapsulate -nitroso--acetyl-d,l-penicillamine (SNAP) to produce SNAP@HMMN with dual capacities of selective peroxynitrite removal and controllable NO release. Featuring a large corneal permeability, the well-designed SNAP@HMMN can achieve trans-corneal delivery to reach the target trabecular meshwork (TM)/Schlemm's canal (SC) site. Upon light irradiation, the intraocular pressure (IOP) is appropriately lowered in an adjustable and long-lasting manner while the outflow tissues are protected from nitrative damage, which is expected to realize precision on-demand glaucoma therapy with little biosafety concern, promising significant clinical translational potential.
Topics: Humans; Nitric Oxide; Peroxynitrous Acid; Nanomedicine; Glaucoma; Intraocular Pressure
PubMed: 37906948
DOI: 10.1021/acsnano.3c02685 -
Journal of Colloid and Interface Science Jan 2024The emergence of antibiotic-resistant bacteria poses a pressing threat to global health and is a leading cause of healthcare-related morbidity and mortality. Herein, we...
The emergence of antibiotic-resistant bacteria poses a pressing threat to global health and is a leading cause of healthcare-related morbidity and mortality. Herein, we report the fabrication of medical-grade polymers incorporated with a dual-action S-nitroso-N-acetylpenicillamine-functionalized ampicillin (SNAPicillin) conjugated molecule through a solvent evaporation process. The resulting SNAPicillin-incorporated polymer materials act as broad-spectrum antibacterial surfaces that improve the administration efficacy of conventional antibiotics through the targeted release of both nitric oxide and ampicillin. The polymer surfaces were characterized by scanning electron microscopy and static contact angle measurements. The nitric oxide (NO) release profile and diffusion of SNAPicillin from polymers were quantified using a chemiluminescence-based nitric oxide analyzer (NOA) and ultraviolet-visible (UV-vis) spectroscopy. As a result, the films had up to 2.96 × 10 mol cm of total NO released within 24 hr. In addition, >79 % of the SNAPicillin reservoir was preserved in the polymers after 24 hr of incubation in the physiological environment, indicating their longer-term NO release ability and therapeutic window for antibacterial effects. The SNAPicillin-incorporated polymers reduced the viability of adhered bacteria in culture, with >95 % reduction found against clinically relevant strains of Staphylococcus aureus (S. aureus). Furthermore, SNAPicillin-modified surfaces did not elicit a cytotoxic effect toward 3T3 mouse fibroblast cells, supporting the material's biocompatibility in vitro. These results indicate that the complementary effects of NO-release and ampicillin in SNAPicillin-eluting polymers can enhance the properties of commonly infected medical device surfaces for antibacterial purposes.
Topics: Animals; Mice; Anti-Bacterial Agents; Nitric Oxide; Polymers; Staphylococcus aureus; S-Nitroso-N-Acetylpenicillamine; Ampicillin
PubMed: 37832467
DOI: 10.1016/j.jcis.2023.09.188 -
Analytical Chemistry Oct 2023The recognition and separation of chiral isomers are of great importance in both industrial and biological applications. In this study, a chiral recognition system based...
The recognition and separation of chiral isomers are of great importance in both industrial and biological applications. In this study, a chiral recognition system based on electrochemiluminescence was established for the detection of penicillamine (PA) enantiomers. The system utilized a homochiral [Zn(BDC)(d-lac)] (Zn-BL) platform for the uniform distribution of Ru(bpy) nanoparticles, effectively mitigating aggregation-caused quenching. The chiral recognition ability of Zn-BL was tested to distinguish between PA enantiomers, and the results indicated a substantial increase in the chiral electrochemiluminescence (ECL) signal when l-PA was present, in contrast to d-PA. The mechanism underlying ECL chiral discrimination was investigated using water contact angle measurements, DFT calculations, and electrochemical characterization. The system exhibited high selectivity, stability, and reproducibility for PA enantiomer detection. Furthermore, the proposed method can accurately identify one enantiomer of PA in a mixture. This study provides a reliable and sensitive approach for achieving the highly selective detection of chiral molecules.
PubMed: 37725048
DOI: 10.1021/acs.analchem.3c02516 -
Cureus Aug 2023Introduction Wilson's disease (WD) is a rare and underdiagnosed genetic disorder caused by anomalous tissue copper deposition, and for which epidemiological studies,...
Introduction Wilson's disease (WD) is a rare and underdiagnosed genetic disorder caused by anomalous tissue copper deposition, and for which epidemiological studies, specifically in Portugal, are scarce. Objectives This study aimed to evaluate the prevalence and incidence of WD and provide a description of its main clinical and laboratory features. Methods A retrospective study was carried out, with a search between 1995 and 2015, of all patients with a minimum follow-up of three months and birth confirmed in the northern region of Portugal, with an estimated population of 3,689,682 inhabitants. Database collection was based on the Portuguese National Health Service's clinical coding system, relying on clinical data from 13 northern Portuguese hospitals, liver biopsy histology results, and hospital prescription records. Clinical and biochemical correlations were statistically assessed using chi-square, Mann-Whitney U, Friedman, and Wilcoxon tests. Results Over the 20-year period, a prevalence of 1:37.000 and an incidence of one per million person-year was found. A total of 94 patients were analyzed, with a slight male predominance (53%), the majority with the onset of clinical manifestations in pediatric age (56%), with a median age at diagnosis of 16.6 years (interquartile range of 12.3-20,.8 years). Most patients presented with predominant liver disease (54.8%), with more than a third with cirrhosis; mixed hepatic and neurological manifestations in 17.9%; and mainly neurological symptoms in 10.7% of the patients. Neurological impairment was strongly associated with delayed development of the manifestations of the disease (p = 0.001) and also a higher detection of Kayser-Fleischer rings (p < 0.001), present in 27.0% of the patients. Regarding therapy, penicillamine has been the most widely used, with adverse reactions reported in 24.8%. At six and 12 months after initiation of therapy, a significant decrease in liver enzymes was found (ALT: p = 0.002; AST: p = 0.002, respectively), but no significant reduction was observed in urinary copper excretion. Conclusion This was one of the first studies regarding WD prevalence in a Portuguese population, contributing to a better understanding of the epidemiology, diagnosis, and management of WD in the northern region of Portugal. WD should be considered in any individual with unexplained hepatic or neurological manifestations, and initial symptoms may manifest at an early age, even in children less than five years old. A high percentage of patients were identified in the early stages of the disease by asymptomatic elevation of transaminases. Following copper chelation therapy, cytolysis markers appear to be more sensitive indicators of treatment response.
PubMed: 37724235
DOI: 10.7759/cureus.43718 -
Advanced Materials (Deerfield Beach,... Dec 2023The chemical, physical and biological effects of chiral nanomaterials have inspired general interest and demonstrated important advantages in fundamental science. Here,...
The chemical, physical and biological effects of chiral nanomaterials have inspired general interest and demonstrated important advantages in fundamental science. Here, chiral iron oxide supraparticles (Fe O SPs) modified by chiral penicillamine (Pen) molecules with g-factor of ≈2 × 10 at 415 nm are fabricated, and these SPs act as high-quality magnetic resonance imaging (MRI) contrast agents. Therein, the transverse relaxation efficiency and T -MRI results demonstrated chiral Fe O SPs have a r relaxivity of 157.39 ± 2.34 mM ·S for D-Fe O SPs and 136.21 ± 1.26 mM ·S for L-Fe O SPs due to enhanced electronic transition dipole moment for D-Fe O SPs compared with L-Fe O SPs. The in vivo MRI results show that D-Fe O SPs exhibit two-fold lower contrast ratio than L-Fe O SPs, which enhances targeted enrichment in tumor tissue, such as prostate cancer, melanoma and brain glioma tumors. Notably, it is found that D-Fe O SPs have 7.7-fold higher affinity for the tumor cell surface receptor cluster-of-differentiation 47 (CD47) than L-Fe O SPs. These findings uncover that chiral Fe O SPs act as a highly effective MRI contrast agent for targeting and imaging broad tumors, thus accelerating the practical application of chiral nanomaterials and deepening the understanding of chirality in biological and non-biological environments.
Topics: Male; Humans; Ferric Compounds; Contrast Media; Brain Neoplasms; Glioma; Magnetic Resonance Imaging
PubMed: 37721365
DOI: 10.1002/adma.202308198 -
Analytical Chemistry Sep 2023Enantioselective identification of chiral molecules is regarded as one of the key issues in biological and medical sciences because of their configuration-dependent...
Enantioselective identification of chiral molecules is regarded as one of the key issues in biological and medical sciences because of their configuration-dependent effects on biological systems. In this study, we developed an electrochemical platform based on a tandem recognition-reaction zone design in TiO nanochannels for the specific recognition of reducing enantiomers. In this system, MIL-125(Ti) Ti-metal-organic frameworks, grown in TiO nanochannels, provided a homochiral recognition environment postmodification with l-tartaric acid (l-TA); MnO nanosheets possessing both glucose oxidase (GOD)- and peroxidase (POD)-mimicking activities served as the target-reactive zone at the end of the nanochannels. The use of penicillamine (Pen) enantiomers as model-reducing targets facilitated the passage of d-Pen through the homochiral recognition zone, owing to its lower affinity with l-TA. The passed Pen molecules reached the responsive zone and induced a target concentration-dependent MnO disassembly. Such target recognition event impaired the cascade GOD- and POD-like activities of MnO. Combining the enantioselectivity of the recognition nanochannels with the cascade enzyme-like activity of MnO toward glucose and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate), the quantitative identification of l- and d-Pen was achieved through the changes in transmembrane ionic current induced by the generated charged products. This recognition-reaction zone design paves an effective way for developing a promising electrochemical platform for the identification of reducing enantiomers with improved selectivity and sensitivity.
Topics: Manganese Compounds; Oxides; Stereoisomerism; Glucose Oxidase; Penicillamine
PubMed: 37699410
DOI: 10.1021/acs.analchem.3c03089