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1.
J Colloid Interface Sci ; 678(Pt A): 427-435, 2025 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-39213995

RESUMO

Metal-free carbon-based nanozymes often exhibit superior chemical stability and detection reliability compared to their metal-doped counterparts. However, their catalytic activity remains an area ripe for further enhancement. Herein, we successfully prepared a chlorine (Cl)-modified, metal-free, and porous N-doped carbon nanozyme (Clx-pNC) via NaCl molten etching. The incorporation of Cl induced an increase in the intrinsic defects of sp3-hybridized carbon within Clx-pNC and optimized the electronic structure of the N-connected carbon atoms. Remarkably, the peroxidase (POD)-like activity of Clx-pNC was enhanced twelvefold compared to porous N-doped carbon (pNC). Theoretical simulations highlighted that the introduction of Cl not only promoted H2O2 adsorption but also lowered the energy barrier for its decomposition, facilitating the generation of active intermediates and thus boosting POD-like activity. Based on the POD mimic activity of Clx-pNC, we developed a colorimetric platform for OPs detection utilizing a cascade amplification strategy. This work provides insights into the rational design of carbon-based nanozymes and the development of nanozyme-based colorimetric biosensors.

2.
Angew Chem Int Ed Engl ; : e202414894, 2024 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-39503072

RESUMO

An enzyme-mimicking catalytic system has been established using a singular palladium-based octahedral cage as the supramolecular reactor, deftly unlocking off-on-off selectivity in the semi-hydrogenation of alkynes. Water serves as a critical regulator, modulating the catalyst states, reaction rates, and endpoints. The choice of solvent system influences the activity of host-guest binding and the reaction types of homogeneous and heterogeneous catalysis, effectively modifying the reaction steps involved in the Z→E isomerization during the semi-hydrogenation of alkynes. Kinetic and inhibition experiments indicate that the catalyst mimics the binding and activation characteristics of enzymes towards substrates, enabling selective transformations within the confined enzyme-mimicking environment. The utility of this switchable cage-confined catalysis has been demonstrated in the synthesis and modification of complex biologically active molecules with controllable E/Z selectivity. This work sheds light on the design and control of artificial supramolecular counterparts of enzymes, offering fundamental insights into the factors influencing the activity and catalytic selectivity of biological macromolecules.

3.
Adv Mater ; : e2413981, 2024 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-39491508

RESUMO

Deciphering inter- and intracellular signaling pathways is pivotal for understanding the intricate communication networks that orchestrate life's dynamics. Communication models involving bottom-up construction of protocells are emerging but often lack specialized compartments sufficiently robust and hierarchically organized to perform spatiotemporally defined signaling. Here, the modular construction of communicating polymer-based protocells designed to mimic the transduction of information in retinal photoreceptors is presented. Microfluidics is used to generate polymeric protocells subcompartmentalized by specialized artificial organelles. In one protocell population, light triggers artificial organelles with membrane-embedded photoresponsive rotary molecular motors to set off a sequence of reactions starting with the release of encapsulated signaling molecules into the lumen. Intercellular communication is mediated by signal transfer across membranes to protocells containing catalytic artificial organelles as subcompartments, whose signal conversion can be modulated by environmental calcium. Signal propagation also requires selective permeability of the diverse compartments. By segregating artificial organelles in distinct protocells, a sequential chain of reactions mediating intercellular communication is created that is further modulated by adding extracellular messengers. This connective behavior offers the potential for a deeper understanding of signaling pathways and faster integration of proto- and living cells, with the unique advantage of controlling each step by bio-relevant signals.

4.
Eur J Paediatr Neurol ; 53: 95-103, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39423467

RESUMO

BACKGROUND: The development of unicentric pediatric acute stroke protocols has improved stroke diagnosis and treatment. The impact of the implementation of a multicentric Pediatric Stroke Code (PSC) remains unknown. AIM: to describe the characteristics of the PSC activations and identify clinical features associated with stroke compared to stroke mimics in children in whom a multicentric PSC had been activated and compare them to reported monocentric PSC results. METHODS: Observational, retrospective, case and control multicentric study, performed in the Pediatric Emergency Department (PED) of the three Primary Pediatric Stroke Centers (PPSCs) in Madrid (Spain). Study population corresponded to children between 28 days and 16 years old in whom PSC was activated that consulted or were referred to any of the PPSC PED between March 2019 and June 2022. The main outcome was to compare the characteristics of patients with final diagnosis of stroke versus stroke mimics, among all patients for which PSC had been activated. Logistic regression modeling was used to investigate associations between independent variables and stroke diagnosis. Odds ratio (ORs) and 95 % confidence intervals (95%CIs) were estimated. RESULTS: PSC was activated in 196 patients. Stroke was confirmed in 39 patients (19.9 %): 20 (10.2 %) had an ischemic stroke and 19 (9.7 %) a hemorrhagic stroke. Stroke mimics represented 80.1 % of the PSC activations. Migraine was the most frequent stroke mimic (38.3 %). Time from symptom onset to brain imaging was 233.00 min (IQR 153.00-373.00) when patients self-presented at the PPSC compared to 231.00 min (IQR 129.00-400.00) when PSC was triggered at other settings (p0.580). Five patients (25.3 %) were eligible for hyperacute recanalization treatment. Low level of consciousness (OR4.373, 95%IC 0.247-0.652, p < 0.001), sensory disruption/motor disability of face/limbs (OR3.633, 95%IC 0.103-0.349, p < 0.001), aphasia (OR2.311, 95%IC 0.023-0.284, p0.022) and altered mental status (OR2.517, 95%IC 0.043-0.357, p0.013) were associated with an increased probability of stroke. CONCLUSION: multicentric PSC achieved similar results to previously reported unicentric PSCs, showing the feasibility of such an organization.

5.
J Agric Food Chem ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39363717

RESUMO

Chlorantraniliprole (CHL), a favored agricultural insecticide, is renowned for its high efficiency and broad-spectrum effectiveness against lepidoptera insects. However, the urgency for new insecticide development is underscored by the intricate multistep preparation process and modest overall yields of CHL, along with the escalating challenge of insect resistance. In response, we have crafted CHL mimics from proline employing computer-aided drug design. Molecular docking analysis of CHL's interactions with the ryanodine receptor (RyR) revealed that the nitrogen atom within the pyrazole moiety does not engage in pivotal interactions. Its removal may not abolish bioactivity entirely but could substantially simplify the synthetic process, thereby enhancing atom economy. This revelation prompted the exclusion of nitrogen and the subsequent formation of a pyrrole ring, enabling the meticulous design of synthetic pathways characterized by cost-effective precursors, streamlined synthesis, the avoidance of toxic reagents, minimal instrumentation, and high yields in the pursuit of innovative RyR modulators. Among these modulators, A1 and B1, obtained with yields exceeding 60%, showcased exceptional insecticidal potency, with LC50 values spanning from 0.12 to 1.47 mg L-1 against P. xylostella and M. separate. The inhibitory effects of these two compounds on insect detoxification enzymes imply a reduced likelihood of eliciting resistance in comparison to CHL, a finding further corroborated by their insecticidal potency against resistant pests. Moreover, molecular docking, MD simulations, and DFT calculations provided valuable structural insights, potentially unraveling the superior insecticidal activity of these two molecules, and thus paving the way for developing more potent insecticides.

6.
Sci Rep ; 14(1): 24501, 2024 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-39424621

RESUMO

The RNA binding protein Human Antigen R (HuR) has been identified as a main regulator of the innate immune response and its inhibition can lead to beneficial anti-inflammatory effects. To this aim, we previously synthesized a novel class of small molecules named Tanshinone Mimics (TMs) able to interfere with HuR-RNA binding, and that dampen the LPS-induced immune response. Herein, we present a novel series of TMs, encompassing thiophene 3/TM9 and 4/TM10, furan 5/TM11 and 6/TM12, pyrrole 7b/TM13, and pyrazole 8. The furan-containing 5(TM11) showed the greatest inhibitory effect of the series on HuR-RNA complex formation, as suggested by RNA Electromobility Shift Assay and Time-Resolved FRET. Molecular Dynamics Calculation of HuR - 5/TM11 interaction, quantum mechanics approaches and Surface Plasmon Resonance data, all indicates that, within the novel heteroaryl substituents, the furan ring better recapitulates the chemical features of the RNA bound to HuR. Compound 5/TM11 also showed improved aqueous solubility compared to previously reported TMs. Real-time monitoring of cell growth and flow cytometry analyses showed that 5/TM11 preferentially reduced cell proliferation rather than apoptosis in murine macrophages at immunomodulatory doses. We observed its effects on the innate immune response triggered by lipopolysaccharide (LPS) in macrophages, showing that 5/TM11 significantly reduced the expression of proinflammatory cytokines as Cxcl10 and Il1b.


Assuntos
Abietanos , Macrófagos , Animais , Camundongos , Abietanos/farmacologia , Abietanos/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , Inflamação/tratamento farmacológico , Proteína Semelhante a ELAV 1/metabolismo , Furanos/farmacologia , Furanos/química , Humanos , Quimiocina CXCL10/metabolismo , Células RAW 264.7 , Simulação de Dinâmica Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Apoptose/efeitos dos fármacos , Solubilidade
7.
Heliyon ; 10(19): e38602, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39403531

RESUMO

Background: Early recognition and prediction of stroke mimics (SM) can avoid inappropriate recanalization therapy and delay in the management of SM etiology. The purpose of this study is to screen the predictors for SM and develop a novel predictive nomogram model for predicting SM. Meanwhile, the diagnostic performance of the nomogram model was evaluated and validated. The diagnostic efficacy of the nomogram model was also compared with four other SM structured scales. Methods: The clinical data of eligible patients were retrospectively enrolled as training datasets from January 2020 to December 2021; and the clinical data of eligible patients were prospectively enrolled as validation datasets from February to December 2022 in stroke center, Shengjing hospital, respectively. Univariate analysis and Lasso regression were used to select the optimal predictors for the training set, and a nomogram model was constructed by multivariate logistics regression, predictive scoring based on nomogram model is performed for each subject suffering from suspected acute ischemic stroke. Area under the curve (AUC), Hosmer-Lemeshow goodness-of-fit test, Calibration curve, decision curve analysis (DCA), clinical impact curve (CIC) analysis and bootstrap sampling were performed to assess and validate the predictive performance and clinical utility of the nomogram model, and the DeLong test was used to compare the overall diagnostic performance of the nomogram model with the other four structured SM scales. The Delong test was also conducted to assess the external reliability of the SM nomogram model by comparing the predictive diagnostic performance of the validation set with the training set. Additionally, the Calibration curve was utilized to evaluate the diagnostic calibration capability of the SM nomogram model in the validation set. Results: 703 eligible patients (68 with SM, accounting for 9.7 %) were assigned to the training set, while 301 patients (26 with SM, accounting for 8.6 %) were assigned to the validation set. A nomogram model was then developed using these six parameters (SBP, history of epilepsy, isolated dizziness, isolated sensory impairment, headache, and absence of speech impairment symptoms), a dynamic web-based version of the nomogram was subsequently created. Comparing with four other scales, the nomogram model showed the highest overall diagnostic performance (AUC = 0.929, 95%CI = 0.908-0.947). The Hosmer-Lemeshow goodness-of-fit test was conducted to assess the agreement between the predicted SM values from the model and the observed SM values. The results of the test indicated a favorable consistency (χ2 = 9.299, P = 0.3177) between the predicted and observed SM. The results obtained from the analysis of the Calibration curve, DCA curve, and CIC analysis suggested that the nomogram possesses a favorable predictive capacity and superior clinical usefulness. Furthermore, the external validation demonstrated that there is no significant difference in the overall predictive diagnostic performance between the validation set and training set (0.929 vs 0.910, P > 0.05), thereby confirming the favorable stability of the nomogram model. Conclusion: Our study firstly proposed a nomogram prediction approach based on the clinical features of SM, which could effectively predict the occurrence of SM. The utilization of the nomogram in stroke center proves advantageous for the identification and evaluation of SM, thereby enhancing diagnostic decision-making and strategies employed for suspected acute stroke patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39404798

RESUMO

Research on lung surfactant has exerted a great impact on newborn respiratory care and significantly improved survival and outcome of preterm infants with respiratory distress syndrome (RDS) due to surfactant deficiency because of lung immaturity. Current clinical, animal-derived, surfactants are among the most widely tested compounds in neonatology However, limited availability, high production costs, and ethical concerns about using animal-derived products constitute important limitations in their universal application. Synthetic lung surfactant offers a promising alternative to animal-derived surfactant by providing improved consistency, quality and purity, availability and scalability, ease of production and lower costs, acceptance, and safety for the treatment of neonatal RDS and other lung conditions. Third-generation synthetic surfactants built around surfactant protein B (SP-B) and C (SP-C) peptide mimics stand at the forefront of innovation in neonatal pulmonary medicine, while nasal continuous positive airway pressure (nCPAP) has become the standard non-invasive respiratory support for preterm infants. nCPAP can prevent the risk of chronic lung disease (bronchopulmonary dysplasia) and reduce lung injury by avoiding intubation and mechanical ventilation, is a relatively simple technique and can be initiated safely and effectively in the delivery room. Combining nCPAP with noninvasive, preferably aerosol, delivery of synthetic lung surfactant promises to improve respiratory outcomes for preterm infants, especially in low-and-middle income countries.

9.
Chemistry ; : e202403483, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39417606

RESUMO

Nonmetal-containing peroxidase enzymes, including glutathione peroxidase (GPx), and peroxiredoxins, control cellular redox levels by catalyzing the reduction of H2O2. The remarkably higher reactivity of GPx enzyme as compared to the fully dissociated synthetic selenolate/thiolate molecule is probably due to the dual-attack on the peroxide bond (HO1-O2H) by the enzyme; The first one is a nucleophilic attack of the selenolate/thiolate moiety to O1 atom and the second attack at the O2 atom of the peroxide bond by the acidic "parked proton" from Trp or His residue present at the enzyme's active site, leading to the facile cleavage of O-O bond. Herein, we report two synthetic compounds (1 and 2), having a selenolate (Se-) and a proton donor (imidazolium or -COOH group) moieties, which showed excellent GPx-like activity via dual-attack on the peroxide bond. The combined effect of selenolate moiety that donates electrons to the antibonding orbital of O1-O2 bond and the imidazolium or carboxylic acid moiety at the side chain that forms a strong H-bonding with the O2 atom facilitates O-O bond cleavage of H2O2 more efficiently. 1 and 2 exhibit remarkable ability in protecting Cu(I)-complex [TpmCu(CH3CN)]+ (9) against H2O2 by acting as a sacrificial antioxidant, thereby preventing metal-mediated ROS production.

10.
Adv Healthc Mater ; : e2402659, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39388414

RESUMO

The World Health Organization has warned that without effective action, deaths from drug-resistant bacteria can exceed 10 million annually, making it the leading cause of death. Conventional antibiotics are becoming less effective due to rapid bacterial drug resistance and slowed new antibiotic development, necessitating new strategies. Recently, materials with catalytic/enzymatic properties, known as nanozymes, have been developed, inspired by natural enzymes essential for bacterial eradication. Unlike recent literature reviews that broadly cover nanozyme design and biomedical applications, this review focuses on the latest advancements in nanozymes for combating bacterial drug resistance, emphasizing their design, structural characteristics, applications in combination therapy, and future prospects. This approach aims to promote nanozyme development for combating bacterial drug resistance, especially towards clinical translation.

11.
J Hazard Mater ; 480: 136294, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39471630

RESUMO

As concerns about environmental pollution grow, the rapid identification and quantification of pollutants have become increasingly vital. In this work, a series of pyrimidine derivatives-Cu enzyme mimics (Cytosine-Cu, Cytidine-Cu, and CMP-Cu) with laccase- and peroxidase-like activity were prepared through the coordination of Cu2+ with different pyrimidine derivatives (PDs). The PDs-Cu enzyme mimics contain high levels of Cu+ and N - Cu coordination structures, which provide sufficient catalytic sites for the substrates. Compared with natural enzymes and other nanozymes, PDs-Cu demonstrate superior substrate affinity, catalytic efficiency, stability, and resistance to interference. It was found that PDs-Cu enzyme mimics have different catalytic activities towards different phenolic compounds. Therefore, a three-channel colorimetric sensor array (CSA) was successfully developed utilizing PDs-Cu as the sensing elements. The CSA can accurately identify different phenolic compounds and their mixtures in seawater and simulated wastewater. Additionally, a colorimetric method for detecting H2O2 in eye drops was developed, featuring a detection range of 0.1-10.0 µM and a limit of quantification of 0.1 µM. This research not only provides a flexible protocol for regulating the catalytic activity of enzyme mimics, but also provides important inspiration for the development of methods for rapid identification and detection of contaminants in the environmental water.

12.
SAGE Open Med Case Rep ; 12: 2050313X241285664, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39380886

RESUMO

Fat embolism syndrome is a rare clinical entity. The diagnosis is largely clinical, with the imaging studies supporting the clinical diagnosis. Here we present the case of a 19-year-old boy who presented with a tibial fracture and developed sudden onset shortness of breath on the following day. His clinical and investigation findings were suggestive of acute respiratory distress syndrome with fever, tachycardia, and tachypnea along with acute hemoglobin and platelet drop with positive fat globules. According to two clinical criteria, his diagnosis of fat embolism was established. The diagnostic dilemma arose when S1Q3T3 was seen in the electrocardiogram raising a doubt whether it could be a pulmonary embolism.

13.
Cureus ; 16(8): e67351, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39310498

RESUMO

The Collagen Type 4 alpha 1 (COL4A1), is an important component of nearly all vascular basement membranes. Pathogenic mutation of this gene results in varied manifestations. In this report, we describe a two-and-a-half-year-old boy with an eventful perinatal period, global developmental delay, and epileptic spasms. Examination revealed microcephaly, nystagmus, and spasticity in limbs. Electroencephalogram showed multifocal epileptiform discharges and MRI brain demonstrated periventricular white matter changes, intracerebral bleeds, and porencephalic cysts. CT brain showed intracranial calcifications and screening for congenital infection was negative. The molecular genetic evaluation was later confirmed with a heterozygous mutation of the COL4A1 gene on exon 37 (variant - p.Gly1050Ala) with an autosomal dominant inheritance pattern. Currently, the child has developed drug-refractory epilepsy requiring polypharmacy and the ketogenic diet. COL4A1 gene mutations are close mimickers of Cerebral Palsy, hence a high index of suspicion should be exercised while approaching a child with spastic quadriplegia in order to promptly diagnose and manage such children for a better neurological outcome.

14.
Food Chem ; 463(Pt 3): 141399, 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39326316

RESUMO

Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin with widespread contamination. Inspired by lactone hydrolases, a peptide-based enzyme mimetic material for degrading ZEN was developed by combining serine, histidine and glutamate (S/H/E) catalytic triad with pro-hydrophobic self-assembling sequences and oxyanion hole site. Chitosan hybrid membranes were prepared, followed by immobilizing enzyme mimic on the membrane surface to fabricate biocatalytic membrane reactor. The membrane reactor, with good thermal stability and high catalytic activity after repeated use, can be applied to the degradation of ZEN in food. Computer simulation studies of the degradation mechanism indicated that the carbon atom on the lactone bond within ZEN molecule was susceptible to catalytic triplex attack, leading to lactone bond broken, followed by spontaneous decarboxylation to produce dihydroxyphenyl derivatives with greatly reduced binding capacity to the estrogen receptors. This kind of peptide-based enzyme mimetic material would be very promising in degrading mycotoxins in food safety field.

15.
Radiol Case Rep ; 19(11): 5038-5043, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39253041

RESUMO

Magnetic resonance imaging (MRI) is an indispensable tool in neurosurgery, though it sometimes faces challenges such as "tumor mimicry." While intraoperative MRI (iMRI) is widely recognized for its usefulness in achieving maximal safe resection during glioma surgery, instances of tumor mimicry still occur on iMRI. Moreover, reports on tumor mimics observed through iMRI, particularly in low-grade gliomas, remain scarce. In this article, we present a case of oligodendroglioma, where a newly emerged T2 high-signal intensity region on iMRI necessitated differentiation from tumor expansion. A 23-year-old man presented with a newly diagnosed brain tumor and underwent surgical removal. An iMRI taken after tumor removal revealed a newly emerged T2 hyperintense area without diffusion restriction around the resection cavity, which was not observed in the preoperative MRI. Suspecting residual tumor, we performed additional resection. An MRI on the following day confirmed that the T2 hyperintense area identified on the iMRI had been completely resected but also revealed an enlarged T2 high-signal area over a wider region. Histopathology found no tumor cells in the additionally resected area, indicating that the iMRI finding was a tumor mimic. Six months later, the T2 high-signal area around the resection cavity had disappeared on MRI without any additional treatment. This case highlights the challenge of distinguishing between T2 hyperintense mimicry and tumor enlargement during glioma surgery seen on iMRI. Despite the significant value of iMRI, our report underscores the need for careful interpretation in neurosurgical practice, particularly with non-contrast-enhancing tumors.

16.
Ann Med ; 56(1): 2398199, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39233624

RESUMO

The diagnosis of amyotrophic lateral sclerosis (ALS) is based on evidence of upper and lower motor neuron degeneration in the bulbar, cervical, thoracic, and lumbar regions in a patient with progressive motor weakness, in the absence of differential diagnosis. Despite these well-defined criteria, ALS can be difficult to diagnose, given the wide variety of clinical phenotypes. Indeed, the central or peripheral location of the disease varies with a spectrum ranging from predominantly central to exclusively peripheral, symptoms can be extensive or limited to the limbs, bulbar area or respiratory muscles, and the duration of the disease may range from a few months to several decades. In the absence of a specific test, the diagnostic strategy relies on clinical, electrophysiological, biological and radiological investigations to confirm the disease and exclude ALS mimics. The main challenge is to establish a diagnosis based on robust clinical and paraclinical evidence without delaying treatment initiation by increasing the number of additional tests. This approach requires a thorough knowledge of the phenotypes of ALS and its main differential diagnoses.


The diagnosis of amyotrophic lateral sclerosis (ALS) is based on progressive degeneration of upper and lower motor neurons.ALS can be difficult to diagnose due to the wide range of clinical phenotypes (central/peripheral location, symptom distribution, disease duration).A thorough diagnostic strategy including clinical, electrophysiological, biological and radiological investigations is essential to confirm ALS and exclude differential diagnoses.


Assuntos
Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Humanos , Diagnóstico Diferencial , Eletromiografia/métodos
17.
ACS Nano ; 18(37): 25685-25694, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39223090

RESUMO

Phosphates within tumors function as key biomolecules, playing a significant role in sustaining the viability of tumors. To disturb the homeostasis of cancer cells, regulating phosphate within the organism proves to be an effective strategy. Herein, we report single-atom Ce-doped Pt hydrides (Ce/Pt-H) with high phosphatase-like activity for phosphate hydrolysis. The resultant Ce/Pt-H exhibits a 26.90- and 6.25-fold increase in phosphatase-like activity in comparison to Ce/Pt and Pt-H, respectively. Mechanism investigations elucidate that the Ce Lewis acid site facilitates the coordination with phosphate groups, while the surface hydrides enhance the electron density of Pt for promoting catalytic ability in H2O cleavage and subsequent nucleophilic attack of hydroxyl groups. Finally, by leveraging its phosphatase-like activity, Ce/Pt-H can effectively regulate intracellular phosphates to disrupt redox homeostasis and amplify oxidative stress within cancer cells, ultimately leading to tumor apoptosis. This work provides fresh insights into noble-metal-based phosphatase mimics for inducing tumor apoptosis.


Assuntos
Apoptose , Cério , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Cério/química , Cério/farmacologia , Apoptose/efeitos dos fármacos , Humanos , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos
18.
BMC Neurol ; 24(1): 309, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223525

RESUMO

BACKGROUND: Bibrachial amyotrophy associated with an extradural CSF collection and infratentorial superficial siderosis (SS) are rare conditions that may occasionally mimic ALS. Both disorders are assumed to be due to dural tears. CASE PRESENTATION: A 53-year-old man presented with a 7-year history of slowly progressive asymmetric bibrachial amyotrophy. Initially, a diagnosis of atypical motor neuron disease (MND) was made. At re-evaluation 11 years later, upper limb wasting and weakness had further progressed and were accompanied by sensorineural hearing loss. MRI of the brain and spine demonstrated extensive supra- and infratentorial SS (including the surface of the whole spinal cord) as well as a ventral longitudinal intraspinal fluid collection (VLISFC) extending along almost the entire thoracic spine. Osteodegenerative changes were observed at C5-C7 level, with osteophytes protruding posteriorly. The bony spurs at C6-C7 level were hypothesized to have lesioned the dura, causing a CSF leak and thus a VLISFC. Review of the MRI acquired at first evaluation showed that the VLISFC was already present at that time (actually beginning at C7 level), whereas the SS was not. 19 years after the onset of upper limb weakness, the patient additionally developed parkinsonism. Response to levodopa, brain scintigraphy with 123I-ioflupane and brain MRI with nigrosome 1 evaluation were consistent with idiopathic Parkinson's disease (PD). On the latest follow-up 21 years after symptom onset, the VLISFC was unchanged, as were upper arm weakness and wasting. CONCLUSIONS: Based on the long-term follow-up, we could establish that, while the evidence of the VLISFC was concomitant with the clinical presentation of upper limb amyotrophy and weakness, the radiological signs of SS appeared later. This suggests that SS was not per se the cause of the ALS-like clinical picture, but rather a long-term sequela of a dural leak. The latter was instead the causative lesion, giving rise to a VLISFC which compressed the cervical motor roots. Dural tears can actually cause several symptoms, and further studies are needed to elucidate the pathophysiological correlates of "duropathies". Finally, as iron metabolism has been implicated in PD, the co-occurrence of PD with SS deserves further investigation.


Assuntos
Doença dos Neurônios Motores , Siderose , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/diagnóstico por imagem , Siderose/complicações , Siderose/diagnóstico , Siderose/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Diagnóstico Diferencial , Dura-Máter/diagnóstico por imagem , Dura-Máter/patologia
19.
Children (Basel) ; 11(9)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39334635

RESUMO

The phenomenon of child abuse/maltreatment is underestimated and often represents a difficult challenge for healthcare professionals and forensic pathologists who must proceed with the differential diagnosis with accidental or self-induced events, or with lesions due to pathologies that overlap with that of mistreatment, defined as "Mimics". This study presents a case series with the aim of discussing lesions that may mimic signs of physical abuse in children but are due to a different etiology to raise awareness and train healthcare professionals and forensic pathologists on possible confounding factors in order to avoid diagnostic errors. Six cases of "Mimics" out of 418 cases of suspected mistreatment (1.43% of cases) were identified, presenting skin lesions initially classified as injuries of abuse due to their location and type and, in particular, sexual abuse for three cases. Then, the lesions and the subjects, in particular the anamnestic history, were examined by a multidisciplinary team and the diagnosis of genital lichen sclerosus et atrophicus in three cases, and the results of popular healing techniques (i.e., "cupping") in the other three cases were ascertained. These situations require specific skills and a forensic background from healthcare professionals to conduct a correct differential diagnosis and the intervention of a multidisciplinary team to investigate every possible pathology or alternative therapeutic practice that could simulate child abuse. In particular, when "mimics" are due to alternative medicine, it should not strictly be considered child abuse, but professionals must be aware of the hypothesis of mistreatment in case of non-medical indication or potential personal injuries from other crimes, such as illegal practice of the medicine. This awareness is also crucial to direct the child toward appropriate medical care, and it is essential to recognize that these conditions can coexist within the same clinical presentation.

20.
J R Coll Physicians Edinb ; : 14782715241288903, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39345233

RESUMO

Glomus tumour is a rare benign neoplasm arising from specialized neuromyoarterial plexus situated in the subungual region. Here, we present a 36-year-old male who had severe pain in the distal part of left third finger mimicking distal interphalangeal joint arthritis (DIP). On evaluation, he was found to have severe tenderness just distal to the DIP joint line. Also, he had positive cold sensitivity test. MRI showed high-signal intensity lesion in the dorsal aspect of left third digit. Glomus tumour was suspected based on these findings. Surgical excision was done followed by histopathological examination, confirmed the diagnosis. We present this case to raise awareness about this rare condition and the possibility of misinterpreting distal pain as DIP arthritis.

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