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1.
Clin Nucl Med ; 48(2): 112-118, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607361

RESUMO

PURPOSE: The aim of this study was to compare the diagnostic performance of the rabbit visual pattern versus the one endorsed by the EANM/SNMMI for the diagnosis of parkinsonian syndromes in PET/MRI. PATIENTS AND METHODS: The 18F-DOPA PET images of 129 consecutive patients (65 Park+ and 64 controls) with 1 year of clinical follow-up were reviewed independently by 5 experienced readers on the same imaging workstation, blinded to the final clinical diagnosis. Two visual methods were assessed independently, with several days to months of interval: the criteria endorsed by EANM/SNMMI and the "rabbit" shape of the striate assessed on 3D MIP images. The sensitivities, specificities, likelihood ratios, and predictive values of the 2 diagnostic tests were estimated simultaneously by using the "comparison of 2 binary diagnostic tests to a paired design" method. RESULTS: The estimated 95% confidence interval (CI) of sensitivities and specificities ranged from 49.4% to 76.5% and from 83.2% to 97.7%, respectively. The 95% CI estimates of positive and negative likelihood ratios ranged from 3.8 to 26.7 and from 0.26 to 0.56, respectively. The 95% CI estimates of the positive and negative predictive values ranged from 78.1% to 96.7% and from 60.3% to 81.4%, respectively. For all the parameters, no statistical difference was observed between the 2 methods (P > 0.05). The rabbit sign reduced the readers' discrepancies by 25%, while maintaining the same performance. CONCLUSIONS: The rabbit visual pattern appears at least comparable to the current EANM/SNMMI reference procedure for the assessment of parkinsonian syndromes in daily clinical practice, without the need of any image postprocessing. Further multicenter prospective studies would be of relevance to validate these findings.


Assuntos
Transtornos Parkinsonianos , Tomografia por Emissão de Pósitrons , Humanos , Coelhos , Animais , Estudos Prospectivos , Transtornos Parkinsonianos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Sensibilidade e Especificidade , Di-Hidroxifenilalanina
2.
Biomaterials ; 293: 121957, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36549042

RESUMO

Aging population has been boosting the need for orthopedic implants. However, biofilm has been a major obstacle for orthopedic implants due to its insensitivity to antibiotics and tendency to drive antimicrobial resistance. Herein, an antibacterial polypeptide coating with excellent in vivo adhesive capacity was prepared to prevent implants from forming biofilms and inducing acquired antibiotic resistance. A peptide-based copolymer, poly[phenylalanine10-stat-lysine12]-block-3,4-dihydroxy-l-phenylalanine [Poly(Phe10-stat-Lys12)-DOPA] was modularly designed, where poly(Phe10-stat-Lys12) is antibacterial polypeptide with high antibacterial activity, and DOPA provides strong adhesion in both wet and dry microenvironments. Meanwhile, compared to traditional "graft-onto" methods, this antibacterial coating can be facilely achieved by immersing Titanium substrates into antibacterial polypeptide solution for 5 min at room temperature. The poly(Phe10-stat-Lys12)-DOPA polymer showed good antibacterial activity with minimum inhibitory concentrations against S. aureus and E. coli of 32 and 400 µg/mL, respectively. Compared to obvious antimicrobial resistance of S. aureus after continuous treatment with vancomycin, this antibacterial coating doesn't drive antimicrobial resistance upon long-term utilization. Transcriptome sequencing and qPCR tests further confirmed that the antibacterial coating was able to inhibit the expression of multiple peptide resistance factor (mprF) and lipoteichoic acid modification D-alanylation genes (dltB and dltC) that can increase the net positive charge of bacterial cell wall to induce the resistance to cationic antimicrobial peptides. In vivo experiments confirmed that this poly(Phe10-stat-Lys12)-DOPA coating can both effectively prevent biofilm formation through surface contact sterilization and avoid local and systemic infections. Overall, we proposed a facile method for preparing antibacterial orthopedic implants with longer indwelling time and without inducing antimicrobial resistance by coating a polypeptide-based polymer on the implants.


Assuntos
Antibacterianos , Staphylococcus aureus , Antibacterianos/farmacologia , Escherichia coli , Materiais Revestidos Biocompatíveis/farmacologia , Biofilmes , Peptídeos Catiônicos Antimicrobianos/farmacologia , Resistência Microbiana a Medicamentos , Polímeros/farmacologia , Di-Hidroxifenilalanina/farmacologia , Titânio/farmacologia
3.
Int J Mol Sci ; 23(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36499519

RESUMO

Microbial infections remain a global health concern, calling for the urgent need to implement effective prevention measures. Antimicrobial peptides (AMPs) have been extensively studied as potential antimicrobial coating agents. However, an efficient and economical method for AMP production is lacking. Here, we synthesized the direct coating adhesive AMP, NKC-DOPA5, composed of NKC, a potent AMP, and repeats of the adhesive amino acid 3,4-dihydroxyphenylalanine (DOPA) via an intein-mediated protein ligation strategy. NKC was expressed as a soluble fusion protein His-NKC-GyrA (HNG) in Escherichia coli, comprising an N-terminal 6× His-tag and a C-terminal Mxe GyrA intein. The HNG protein was efficiently produced in a 500-L fermenter, with a titer of 1.63 g/L. The NKC-thioester was released from the purified HNG fusion protein by thiol attack and subsequently ligated with chemically synthesized Cys-DOPA5. The ligated peptide His-NKC-Cys-DOPA5 was obtained at a yield of 88.7%. The purified His-NKC-Cys-DOPA5 possessed surface-binding and antimicrobial properties identical to those of the peptide obtained via solid-phase peptide synthesis. His-NKC-Cys-DOPA5 can be applied as a practical and functional antimicrobial coating to various materials, such as medical devices and home appliances.


Assuntos
Anti-Infecciosos , Peptídeos Antimicrobianos , Adesivos/metabolismo , Anti-Infecciosos/química , Di-Hidroxifenilalanina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Peptídeos/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
4.
Biomed Mater ; 18(1)2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36537718

RESUMO

Electrode impedance is one of the greatest challenges facing neural interfacing medical devices and the use of electrical stimulation-based therapies in the fields of neurology and regenerative medicine. Maximizing contact between electronics and tissue would allow for more accurate recordings of neural activity and to stimulate with less power in implantable devices as electric signals could be more precisely transferred by a stable interfacial area. Neural environments, inherently wet and ion-rich, present a unique challenge for traditional conductive adhesives. As such, we look to marine mussels that use a 3,4-dihydroxyphenyl-L-analine (DOPA)-containing proteinaceous excretion to adhere to a variety of substrates for inspiration. By functionalizing alginate, which is an abundantly available natural polymer, with the catechol residues DOPA contains, we developed a hydrogel-based matrix to which carbon-based nanofiller was added to render it conductive. The synthesized product had adhesive energy within the range of previously reported mussel-based polymers, good electrical properties and was not cytotoxic to brain derived neural precursor cells.


Assuntos
Bivalves , Células-Tronco Neurais , Animais , Hidrogéis/química , Adesivos/química , Proteínas/química , Polímeros/química , Di-Hidroxifenilalanina/química
5.
Int J Mol Sci ; 23(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36499690

RESUMO

Vitiligo is a hypopigmentation disease characterized by melanocyte death in the human epidermis. However, the mechanism of vitiligo development and repigmentation is largely unknown. Dermal fiber components might play an important role in vitiligo development and repigmentation. Indeed, our preliminary study demonstrated that elastin fibers were decreased in vitiliginous skin, suggesting that the elastin fiber is one of the factors involved in vitiligo development and repigmentation. To confirm our hypothesis, we investigated whether elastin fibers can be restored after treatment using phototherapy and/or autologous skin transplantation. Punch biopsies from 14 patients of stable nonsegmental vitiligo vulgaris were collected from nonlesional, lesional, and repigmented skin, and processed to dopa and combined dopa-premelanin reactions. Melanocytes positive to the dopa reaction and melanoblasts/melanocytes positive to the combined dopa-premelanin reaction were surveyed. Moreover, elastin fibers were detected by Victoria blue staining. Numerous melanocytes and melanoblasts were observed in the epidermis of repigmented skin after the treatment. Moreover, in the dermis of repigmented skin, elastin fibers were completely recovered or even upregulated. These results suggest that melanocyte loss in the vitiliginous skin, as well as melanocyte differentiation in repigmented skin, may be at least in part regulated by elastin fibers in the dermis.


Assuntos
Hipopigmentação , Vitiligo , Humanos , Vitiligo/terapia , Vitiligo/patologia , Melanócitos/patologia , Pele/patologia , Pigmentação da Pele , Transplante de Pele , Transplante Autólogo , Di-Hidroxifenilalanina
6.
Mol Pharm ; 19(12): 4654-4664, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36378992

RESUMO

Osteoarthritis (OA) can necessitate surgical interventions to restore the function of the joint in severe cases. Joint replacement surgery is one of the procedures implemented to replace the damaged joint with prosthetic implants in severe cases of OA. However, after successful implantation, a fraction of OA patients still require revision surgery due to aseptic prosthetic loosening. Insufficient osseointegration is one of the factors that contribute to such loosening of the bone implant, which is commonly made from titanium-based materials. Zoledronic acid (ZA), a potent bisphosphonate agent, has been previously shown to enhance osseointegration of titanium implants. Herein, we fabricated ZA/Ca composites using a reverse microemulsion method and coated them with 1,2-dioleoyl-sn-glycero-3-phosphate monosodium salt (DOPA) to form ZA/Ca/DOPA composites. Titanium alloy screws were subsequently dip-coated with a suspension of the ZA/Ca/DOPA composites and poly(lactic-co-glycolic) acid (PLGA) in chloroform to yield Za/PLGA-coated screws. The coated screws exhibited a biphasic in vitro release profile with an initial burst release within 48 h, followed by a sustained release over 1 month. To assess their performance in vivo, the Za/PLGA screws were then implanted into the tibiae of Sprague-Dawley rats. After 8 weeks, microCT imaging showed new bone growth along the medullary cavity around the implant site, supporting the local release of ZA to enhance bone growth around the implant. Histological staining further confirmed the presence of new mineralized medullary bone growth resembling the cortical bone. Such local medullary growth represents an opportunity for future studies with alternative coating methods to fine-tune the local release of ZA from the coating and enhance complete osseointegration of the implant.


Assuntos
Osseointegração , Titânio , Ratos , Animais , Ácido Zoledrônico , Ratos Sprague-Dawley , Próteses e Implantes , Desenvolvimento Ósseo , Di-Hidroxifenilalanina , Materiais Revestidos Biocompatíveis/farmacologia
7.
J Enzyme Inhib Med Chem ; 37(1): 2786-2792, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36210544

RESUMO

A ß-carbonic anhydrase (CA, EC 4.2.1.1) previously annotated to be present in the genome of Staphylococcus aureus, SauBCA, has been shown to belong to another pathogenic bacterium, Mammaliicoccus (Staphylococcus) sciuri. This enzyme, MscCA, has been investigated for its activation with a series of natural and synthetic amino acid and amines, comparing the results with those obtained for the ortholog enzyme from Escherichia coli, EcoCAß. The best MscCA activators were D-His, L- and D-DOPA, 4-(2-aminoethyl)-morpholine and L-Asn, which showed KAs of 0.12 - 0.89 µM. The least efficient activators were D-Tyr and L-Gln (KAs of 13.9 - 28.6 µM). The enzyme was also also inhibited by anions and sulphonamides, as described earlier. Endogenous CA activators may play a role in bacterial virulence and colonisation of the host which makes this research topic of great interest.


Assuntos
Anidrases Carbônicas , Aminas/química , Aminoácidos/química , Anidrases Carbônicas/metabolismo , Di-Hidroxifenilalanina , Estrutura Molecular , Morfolinas , Staphylococcus aureus/metabolismo , Sulfonamidas
8.
Endocrine ; 78(2): 380-386, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36203032

RESUMO

PURPOSE: Bone metastases (BM) affect 10-30% of patients with small intestine neuroendocrine tumors (siNET), but little descriptive data are available regarding their distribution throughout the skeleton or potential risk factors. Aim of the study is to better describe the imaging characteristics, distribution, and risk factors of siNET bone metastases using 18F-FDOPA PET/CT. METHODS: All patients with well-differentiated siNET who underwent an 18F-DOPA PET/CT examination in our institution were retrospectively screened between October 2017 and February 2020. Location, SUVmax and CT density of each BM were collected. Sex, metabolic tumor volume (MTV) excluding bone, and metastatic sites other than bone were studied to determine risk factors of BM. RESULTS: Among the 69 patients included, 11 patients (15.9%) presented BM on 18F-FDOPA (65 metastases). The most frequently involved sites were: thoracic spine, pelvic bones and ribs. About 64% of patients presented multiple BM. On coupled CT scan, 63% of BM were not visible. Using an optimal threshold of 19.2 ml, MTV was an independent predictor of BM (p = 0.004) with a derived sensitivity of 100% [65.0-100.0] and a specificity of 70.9% [57.7-81.2]. Hepatic metastatic involvement was also a significant predictor of BM (p = 0.044). CONCLUSION: The development of BM in siNETs appears to be a late event, occurring in patients with a high tumor burden and hepatic involvement. They are often multiple and predominate in the axial skeleton.


Assuntos
Neoplasias Ósseas , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Di-Hidroxifenilalanina , Compostos Radiofarmacêuticos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Fatores de Risco , Fluordesoxiglucose F18
9.
Nat Commun ; 13(1): 5771, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36182948

RESUMO

Marine mussels achieve strong underwater adhesion by depositing mussel foot proteins (Mfps) that form coacervates during the protein secretion. However, the molecular mechanisms that govern the phase separation behaviors of the Mfps are still not fully understood. Here, we report that GK-16*, a peptide derived from the primary adhesive protein Mfp-5, forms coacervate in seawater conditions. Molecular dynamics simulations combined with point mutation experiments demonstrate that Dopa- and Gly- mediated hydrogen-bonding interactions are essential in the coacervation process. The properties of GK-16* coacervates could be controlled by tuning the strength of the electrostatic and Dopa-mediated hydrogen bond interactions via controlling the pH and salt concentration of the solution. The GK-16* coacervate undergoes a pH induced liquid-to-gel transition, which can be utilized for the underwater delivery and curing of the adhesives. Our study provides useful molecular design principles for the development of mussel-inspired peptidyl coacervate adhesives with tunable properties.


Assuntos
Adesivos , Bivalves , Adesivos/química , Animais , Bivalves/química , Di-Hidroxifenilalanina , Hidrogênio , Ligação de Hidrogênio , Peptídeos , Proteínas/química
10.
J Psychopharmacol ; 36(9): 1061-1069, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36164687

RESUMO

BACKGROUND: Current treatments for schizophrenia act directly on dopamine (DA) receptors but are ineffective for many patients, highlighting the need to develop new treatment approaches. Striatal DA dysfunction, indexed using [18F]-FDOPA imaging, is linked to the pathoetiology of schizophrenia. We evaluated the effect of a novel drug, AUT00206, a Kv3.1/3.2 potassium channel modulator, on dopaminergic function in schizophrenia and its relationship with symptom change. Additionally, we investigated the test-retest reliability of [18F]-FDOPA PET in schizophrenia to determine its potential as a biomarker for drug discovery. METHODS: Twenty patients with schizophrenia received symptom measures and [18F]-FDOPA PET scans, before and after being randomised to AUT00206 or placebo groups for up to 28 days treatment. RESULTS: AUT00206 had no significant effect on DA synthesis capacity. However, there was a correlation between reduction in striatal dopamine synthesis capacity (indexed as Kicer) and reduction in symptoms, in the AUT00206 group (r = 0.58, p = 0.03). This was not observed in the placebo group (r = -0.15, p = 0.75), although the placebo group may have been underpowered to detect an effect. The intraclass correlation coefficients of [18F]-FDOPA indices in the placebo group ranged from 0.83 to 0.93 across striatal regions. CONCLUSIONS: The relationship between reduction in DA synthesis capacity and improvement in symptoms in the AUT00206 group provides evidence for a pharmacodynamic effect of the Kv3 channel modulator. The lack of a significant overall reduction in DA synthesis capacity in the AUT00206 group could be due to variability and the low number of subjects in this study. These findings support further investigation of Kv3 channel modulators for schizophrenia treatment. [18F]-FDOPA PET imaging showed very good test-retest reliability in patients with schizophrenia.


Assuntos
Dopamina , Esquizofrenia , Biomarcadores , Corpo Estriado/diagnóstico por imagem , Di-Hidroxifenilalanina/farmacologia , Di-Hidroxifenilalanina/uso terapêutico , Dopamina/farmacologia , Humanos , Tomografia por Emissão de Pósitrons/métodos , Canais de Potássio/farmacologia , Canais de Potássio/uso terapêutico , Reprodutibilidade dos Testes , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Canais de Potássio Shaw
11.
Pharmacol Res ; 185: 106458, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36152740

RESUMO

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.


Assuntos
Cardiopatias , Inflamação , Humanos , Suínos , Animais , Hipóxia , Di-Hidroxifenilalanina
12.
Biomed Mater ; 17(6)2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36108623

RESUMO

Many surgical treatments require a suitable tissue adhesive that maintains its performance in wet conditions and can be applied simultaneously for hard and soft tissues. In the present study, a dual cross-linked tissue adhesive was synthesized by mixing the gelatin methacryloyl (Gel-MA) and gelatin-dopamine conjugate (Gel-Dopa). The setting reaction was based on a photopolymerization process in the presence of a combination of riboflavin and triethanolamine and a chemical cross-linking process attributed to the genipin as a natural cross-linker. Modified gelatin macromolecules were characterized and the best wavelength for free radical generation in the presence of riboflavin was obtained. Tissue adhesives were prepared with 30% hydrogels of Gel-MA and Gel-Dopa with different ratios in distilled water. The gelation occurred in a short time after light irradiation. The chemical, mechanical, physical, and cytotoxicity properties of the tissue adhesives were evaluated. The results showed that despite photopolymerization, chemical crosslinking with genipin played a more critical role in the setting process. Water uptake, degradation behavior, cytotoxicity, and adhesion properties of the adhesives were correlated with the ratio of the components. The SEM images showed a porous structure that could ensure the entry of cells and nutrients into the surgical area. While acceptable properties in most experiments were observed, all features were improved as the Gel-Dopa ratio increased. Also, the obtained hydrogels revealed excellent adhesive properties, particularly with bone even after wet incubation, and it was attributed to the amount of gelatin-dopamine conjugate. From the obtained results, it was concluded that a dual adhesive hydrogel based on gelatin macromolecules could be a good candidate as a tissue adhesive in wet condition.


Assuntos
Gelatina , Adesivos Teciduais , Adesivos/química , Di-Hidroxifenilalanina/química , Dopamina/química , Gelatina/química , Hidrogéis/química , Iridoides , Metacrilatos , Riboflavina , Adesivos Teciduais/química , Água
13.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077375

RESUMO

Glue-type bio-adhesives are in high demand for many applications, including hemostasis, wound closure, and integration of bioelectronic devices, due to their injectable ability and in situ adhesion. However, most glue-type bio-adhesives cannot be used for short-term tissue adhesion due to their weak instant cohesion. Here, we show a novel glue-type bio-adhesive based on the phase separation of proteins and polysaccharides by functionalizing polysaccharides with dopa. The bio-adhesive exhibits increased adhesion performance and enhanced phase separation behaviors. Because of the cohesion from phase separation and adhesion from dopa, the bio-adhesive shows excellent instant and long-term adhesion performance for both organic and inorganic substrates. The long-term adhesion strength of the bio-glue on wet tissues reached 1.48 MPa (shear strength), while the interfacial toughness reached ~880 J m-2. Due to the unique phase separation behaviors, the bio-glue can even work normally in aqueous environments. At last, the feasibility of this glue-type bio-adhesive in the adhesion of various visceral tissues in vitro was demonstrated to have excellent biocompatibility. Given the convenience of application, biocompatibility, and robust bio-adhesion, we anticipate the bio-glue may find broad biomedical and clinical applications.


Assuntos
Adesivos , Di-Hidroxifenilalanina , Polissacarídeos
14.
Biosens Bioelectron ; 218: 114740, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36179630

RESUMO

Efficient monitoring of chiral information of bioactive compounds has gained considerable attention, due to their involvement in different biochemical processes. In this work, we propose a novel dynamic system for the easy and straightforward recognition of chiral redox active molecules and its possible use for the efficient measurement of enantiomeric excess in solution. The approach is based on the synergy between the localized enantioselective oxidation of only one of the two antipodes of a chiral molecule and the produced charge-compensating asymmetric proton flux along a bipolar electrode. The resulting clockwise or anticlockwise rotation is triggered only when the probe with the right chirality is present in solution. The angle of rotation shows a linear correlation with the analyte concentration, enabling the quantification of enantiomeric ratios in mixtures where the two antipodes are present in solution. This device was successfully used to simultaneously measure different ratios of the enantiomers of 3,4-dihydroxyphenylalanine and tryptophan. The versatility of the proposed approach opens up the possibility to use such a dynamic system as a straightforward (bio)analytical tool for the qualitative and quantitative discrimination of different redox active chiral probes.


Assuntos
Técnicas Biossensoriais , Triptofano , Prótons , Estereoisomerismo , Di-Hidroxifenilalanina
15.
Anal Biochem ; 655: 114856, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35964734

RESUMO

Tyrosinase catalyzes the oxidation of l-tyrosine in two stages to produce l-dopa and l-dopaquinone stepwise, and l-dopaquinone is subsequently converted to dopachrome. Most of the conventional analyses subjected only one-step reaction from l-tyrosine to l-dopa or from l-dopa to l-dopaquinone. In this study, kinetic analyses of two-steps oxidation of l-tyrosine with tyrosinase were made by capillary electrophoresis/dynamic frontal analysis (CE/DFA). When l-dopa was introduced into a capillary as a sample plug in a CE/DFA format, the enzymatic oxidation continuously occurred during the electrophoresis, and the product l-dopaquinone was subsequently converted to dopachrome which was detected as a plateau signal. A Michaelis-Menten constant of the second-step kinetic reaction, Km,Do, was determined as 0.45 ± 0.03 mmol L-1. In the analysis of the first-step kinetic reaction from l-tyrosine to l-dopa, l-dopa was not resolved by CE/DFA because both l-tyrosine and l-dopa are electrically neutral. The l-dopa formed and co-migrated at the l-tyrosine zone was calibrated beforehand with the final product of dopachrome detected as a plateau signal. Constantly formed l-dopa was successfully detected as a plateau signal of dopachrome, and a Michaelis-Menten constant of Km,Ty was also determined as 0.061 ± 0.009 mmol L-1 by the CE/DFA. CE/DFA is applicable to two-steps enzymatic reactions.


Assuntos
Monofenol Mono-Oxigenase , Tirosina , Benzoquinonas , Di-Hidroxifenilalanina/análogos & derivados , Eletroforese Capilar , Cinética , Monofenol Mono-Oxigenase/metabolismo
16.
Hell J Nucl Med ; 25(2): 213-215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913869

RESUMO

Unruptured brain arteriovenous malformations (AVM) have a heterogeneous clinical presentation, mainly related to the presence of intracerebral hemorrhage. We report the diagnosis of AVM in a patient with Parkinson's disease (PD), who undergone positron emission tomography/magnetic resonance imaging (PET/MRI) molecular brain imaging with fluorine-18-dihydroxyphenylalanine (18F-DOPA). This case suggests that AVM may be occasionally recognized in molecular imaging studies using positron-emitting amino acids. Magnetic resonance imaging with susceptibility-weighted imaging (SWI) sequences and 3D time of flight (TOF) reconstruction may contribute to manage patients with AVM.


Assuntos
Malformações Arteriovenosas , Tomografia Computadorizada por Raios X , Encéfalo , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons
17.
Colloids Surf B Biointerfaces ; 218: 112731, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35917689

RESUMO

Nerve implants functionalized with growth factors and stem cells are critical to promote neurite outgrowth, regulate neurodifferentiation, and facilitate nerve regeneration. In this study, human umbilical cord mesenchymal stem cells (hUCMSCs) and 3,4-hydroxyphenalyalanine (DOPA)-containing insulin-like growth factor 1 (DOPA-IGF-1) were simultaneously applied to enhance the bioactivity of poly(lactide-co-glycolide) (PLGA) substrates which will be potentially utilized as nerve implants. In vitro and in vivo evaluations indicated that hUCMSCs and DOPA-IGF-1 could synergistically regulate neurite outgrowth of PC12 cells, improve intravital recovery of motor functions, and promote conduction of nerve electrical signals in vivo. The enhanced functional and structural nerve regeneration of injured spinal cord might be mainly attributable to the synergistically enhanced biofunctionality of hUCMSCs and DOPA-IGF-1/PLGA on the bioactive interfaces. Findings from this study demonstrate the potential of hUCMSC-seeded, DOPA-IGF-1-modified PLGA implants as promising candidates for promoting axonal regeneration and motor functional recovery in spinal cord injury treatment.


Assuntos
Fator de Crescimento Insulin-Like I , Traumatismos da Medula Espinal , Animais , Di-Hidroxifenilalanina , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Regeneração Nervosa/fisiologia , Crescimento Neuronal , Poliglactina 910 , Ratos , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapia
18.
ACS Appl Mater Interfaces ; 14(35): 39759-39774, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36006894

RESUMO

Although metal ions, such as silver and gold, have been shown to have strong antimicrobial properties, their potential to have toxic effects on human and environmental health has gained interest with an improved understanding of their mechanisms to promote oxidative stress. Redox control is a major focus of many drug delivery systems and often incorporates an antioxidant as the active pharmaceutical ingredient (API) to neutralize overproduced reactive oxygen species (ROS). Nevertheless, there are still limitations with bioavailability and extended redox control with regard to antioxidant drug delivery. Herein, this study develops a colloidal antioxidant crystal system that dissolves sustainably through polymer stabilization using sodium hyaluronate conjugated with dopamine (HA-dopa). We explore the role of dopamine incorporation into crystal-stabilizing polymers and quantify the balance between drug-polymer interactions and competing polymer-polymer interactions. We propose that this type of analysis is useful in the engineering of and provides insight into the release behavior of polymer-crystal complexes. In developing our crystal complex, N-acetylcysteine (NAC) was used as the model antioxidant to protect against silver ion toxicity. We found that our optimized HA-dopa-stabilized NAC crystals prolong the release time of NAC 5-fold compared to a polymer-free NAC crystal. Therefore, following sublethal exposure to AgNO3, the extended lifetime of NAC was able to maintain normal intracellular ROS levels, modulate metabolic function, mitigate fluctuations in ATP levels and ATP synthase activity, and preserve contraction frequency in engineered cardiac muscle tissue. Furthermore, the protective effects of the HA-dopa-stabilized NAC crystals were extended to a Daphnia magna model where silver-ion-induced change to both cell-level biochemistry and organ function was alleviated. As such, we propose that the packaging of hydrophilic antioxidants as colloidal crystals drastically extends the lifetime of the API, better maintains ROS homeostasis post metal ion exposure, and therefore preserves both intracellular biochemistry and tissue functionality.


Assuntos
Antioxidantes , Dopamina , Acetilcisteína , Trifosfato de Adenosina/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Disponibilidade Biológica , Cristalização , Di-Hidroxifenilalanina , Dopamina/farmacologia , Humanos , Íons , Estresse Oxidativo , Polissacarídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Prata/toxicidade
19.
Int J Biol Macromol ; 220: 1084-1094, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35985397

RESUMO

Hydrogels with fascinating adhesion have been demonstrated great potential in various applications. However, most hydrogels lose their adhesion in wet or underwater environments due to the influence of interfacial water. Inspired by mussel, an underwater adhesive hydrogel was facilely fabricated by introducing electrostatic interactions, which consisted of poly (acrylic acid) (PAA), quaternized xylan (QAX) and tannic acid (TA). In this hydrogel, -COO- from PAA, -N+(CH3)3 from QAX and catechol group from TA resembled amino acids with negative and positive charges and 3,4-dihydroxyphenylalanine units in mussel, which endowed the hydrogels with great underwater adhesion through multiple interactions. Notably, acrylic acid (AA) played a key role in the dispersion of the system. QAX, a biomass derived from plants with excellent properties, worked with PAA to construct hydrogel networks. The resultant hydrogels exhibited excellent mechanical properties including remarkable stretchability (>4000 %) and compressibility. Moreover, the hydrogels had superior UV-blocking (~99.96 %), and showed good adhesion both in air and underwater. The hydrogels can be exploited as a wearable sensor to monitor human motions and even subtle motions, which have the potential to be explored in human health monitoring.


Assuntos
Bivalves , Hidrogéis , Acrilatos , Adesivos/química , Animais , Bivalves/química , Catecóis/química , Di-Hidroxifenilalanina/química , Humanos , Hidrogéis/química , Taninos/metabolismo , Água/metabolismo , Xilanos/metabolismo
20.
Clin Nucl Med ; 47(11): 931-935, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35961651

RESUMO

OBJECTIVE: The aim of this study was to compare 2 imaging tracers, 18 F-DOPA and 18 F-DTBZ, for PET/CT imaging in idiopathic Parkinson disease (PD). METHODS: We recruited 32 PD patients and 12 healthy controls in this study. All subjects underwent both 18 F-DOPA and 18 F-DTBZ PET/CT, and the results were interpreted by visual analysis and semiquantitative analysis (specific uptake ratios [SURs]). A 1-way analysis of variance was used to compare the clinical data and the SURs among the patients at different stages. Regression analysis was performed to analyze the correlation between the SURs and the clinical data. RESULTS: Among the PD patients, there were 7 patients in Hoehn and Yahr stage I, 14 patients in stage II, and 11 patients in stage III. Linear correlation was found in striatal SURs between the 2 tracers ( P < 0.05). In patients of early stages, the striatal SUR decrease percent of 2 tracers had no statistical difference (paired t test, P > 0.05). By initial visual analysis, all the patients were interpreted as positive with 18 F-DBTZ (6 unilaterally, 26 bilaterally), and 31 cases were regarded as positive with 18 F-DOPA (8 unilaterally, 23 bilaterally). After setting the upper limit of SUR images with the putamen SURs of healthy controls (SUR T ), all patients were interpreted as positive with both tracers ( 18 F-DTBZ: 5 unilaterally, 27 bilaterally; 18 F-DOPA: 4 unilaterally, 28 bilaterally). CONCLUSION: 18 F-DTBZ and 18 F-DOPA could reflect the same level of dopaminergic neuron degeneration for PD in early stages, and they have the consistent visual analysis results.


Assuntos
Doença de Parkinson , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos
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