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1.
ACS Appl Mater Interfaces ; 16(15): 19615-19624, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38587106

RESUMO

Introducing component-selective polymer chains onto the surface of a particle is an effective approach to improve the compatibilization efficiency of a particle-based compatibilizer. In this study, two particles with different kinds of component-selective polymer chains that have the same length and similar density but different graft locations were synthesized and their compatibilization effects were comparatively investigated. It was found that compared with the particle with homogeneous PMMA and PP grafts (R-P), the particle with a hemisphere of poly(methyl methacrylate) (PMMA) grafts and other hemisphere of polypropylene (PP) chains (J-P) showed a better compatibilization effect under equal loadings, although both particles exhibited high efficiency. The better compatibilization effect of particles with Janus grafts may be attributed to the stronger entanglements between grafted polymer chains and selective individual components. This work suggests that optimizing the graft location of a particle is an effective strategy for improving its compatibilization efficiency and helpful for the design of advanced particle compatibilizers.

2.
Small ; 20(14): e2305928, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37986102

RESUMO

Information encryption platforms with reliable encryption performance, excellent mechanical performance, and high water retention capacity are highly desired. In this study, a tough double-network hydrogel is designed using the first network of a polyion complex containing lanthanide complexes via one-pot polymerization and the second network of a poly (N-hydroxyethyl acrylamide) (PHEAA) obtained by deep eutectic solvent (DES)-assisted introduction and subsequent photopolymerization. In this system, the pH-induced shape memory function and pH-/wavelength-dependent fluorescence allow the use of the prepared hydrogel as a dual-encryption platform. Owing to its high response reversibility, the hydrogel-based platform exhibits both a high security level and the advantages of rewritability, reprogrammability, and reusability. Additionally, the excellent mechanical properties and water retention capacity owing to the solvent exchange process involving the low-volatility solvent DES and the resulting introduction of the second network of PHEAA offer high practical application value for the hydrogel-based dual encryption platform, demonstrating its potential for information security protection.

3.
Front Immunol ; 14: 1301051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143759

RESUMO

Atherosclerosis is a common cardiovascular disease caused by the abnormal expression of multiple factors and genes influenced by both environmental and genetic factors. The primary manifestation of atherosclerosis is plaque formation, which occurs when inflammatory cells consume excess lipids, affecting their retention and modification within the arterial intima. This triggers endothelial cell (EC) activation, immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation and migration, foam cell formation, lipid streaks, and fibrous plaque development. These processes can lead to vascular wall sclerosis, lumen stenosis, and thrombosis. Immune cells, ECs, and VSMCs in atherosclerotic plaques undergo significant metabolic changes and inflammatory responses. The interaction of cytokines and chemokines secreted by these cells leads to the onset, progression, and regression of atherosclerosis. The regulation of cell- or cytokine-based immune responses is a novel therapeutic approach for atherosclerosis. Statins are currently the primary pharmacological agents utilised for managing unstable plaques owing to their ability to enhance endothelial function, regulate VSMC proliferation and apoptosis by reducing cholesterol levels, and mitigate the expression and activity of inflammatory cytokines. In this review, we provide an overview of the metabolic changes associated with atherosclerosis, describe the effects of inflammatory responses on atherosclerotic plaques, and discuss the mechanisms through which statins contribute to plaque stabilisation. Additionally, we examine the role of statins in combination with other drugs in the management of atherosclerosis.


Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aterosclerose/metabolismo , Apoptose , Citocinas
4.
ACS Appl Mater Interfaces ; 15(38): 44752-44762, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37702740

RESUMO

Physical eutectogels have great potential for applications in many fields due to their electrical conductivity, broad temperature stability, and biocompatibility. However, the preparation of high-performance physical eutectogels in a simple, efficient, and cost-effective way remains a challenge. In this study, a facile but efficient solvent regulation strategy was proposed to construct a highly robust poly(vinyl alcohol) (PVA) physical eutectogel. Hydrogen bonds within the polymer-containing deep eutectic solvent system were dynamically regulated by the introduction-removal of water to induce the formation of a uniform and dense polymer cross-linked network, which imparted excellent mechanical properties to the resulting eutectogel. For the eutectogel with 15 wt % PVA, the tensile strength and toughness were 1.67 MPa and 6.81 MJ m-3, respectively, which were at a high level among existing physical eutectogels. This high-performance eutectogel was available as a strain sensor and exhibited high sensitivity. In addition, this eutectogel can be endowed with a directional muscle-like stretching performance through convenient mechanical training. The easy scalability and low cost made our method an effective strategy for developing high-performance physical eutectogels, which would further promote the application of such materials in areas such as wearable electronics and soft robotics.

5.
Curr Neuropharmacol ; 21(12): 2465-2480, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37464832

RESUMO

Ischemic stroke is the predominant cause of severe morbidity and mortality worldwide. Post-stroke neuroinflammation has recently received increasing attention with the aim of providing a new effective treatment strategy for ischemic stroke. Microglia and astrocytes are major components of the innate immune system of the central nervous system. They can be involved in all phases of ischemic stroke, from the early stage, contributing to the first wave of neuronal cell death, to the late stage involving phagocytosis and repair. In the early stage of ischemic stroke, a vicious cycle exists between the activation of microglia and astrocytes (through astrocytic connexin 43 hemichannels), aggravating neuroinflammatory injury post-stroke. However, in the late stage of ischemic stroke, repeatedly activated microglia can induce the formation of glial scars by triggering reactive astrogliosis in the peri-infarct regions, which may limit the movement of activated microglia in reverse and restrict the diffusion of inflammation to healthy brain tissues, alleviating the neuroinflammatory injury poststroke. In this review, we elucidated the various roles of astrocytes and microglia and summarized their relationship with neuroinflammation. We also examined how astrocytes and microglia influence each other at different stages of ischemic stroke. Several potential therapeutic approaches targeting astrocytes and microglia in ischemic stroke have been reviewed. Understanding the details of astrocytemicroglia interaction processes will contribute to a better understanding of the mechanisms underlying ischemic stroke, contributing to the identification of new therapeutic interventions.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Microglia/metabolismo , AVC Isquêmico/metabolismo , Astrócitos/metabolismo , Doenças Neuroinflamatórias , Acidente Vascular Cerebral/tratamento farmacológico , Inflamação/metabolismo
6.
Aging (Albany NY) ; 15(10): 4481-4497, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37253636

RESUMO

BACKGROUND: Neutrophils play crucial roles in the inflammatory response after acute cerebral infarction (ACI). Previous studies revealed neutrophils are non-homogeneous and can be divided into at least two subtypes, pro-inflammatory and anti-inflammatory, correlated with patients' prognosis. OBJECTIVE: We aimed to explore the correlation between disease severity and peripheral blood neutrophils in patients with ACI and determine whether remote ischemic postconditioning (RIPostC) exerts neuroprotective effects by regulating neutrophils. METHODS: Patients (n = 38) with acute anterior circulation cerebral infarction were assigned to conventional treatment (n = 24; included aspirin, statins, neuro nutrition drugs, and circulation improvement drugs) or RIPostC (n = 14; 7-day ischemia adaptation [complete ischemia of both upper extremities for 5 minutes followed by remission for 5 minutes, 5 repeated cycles, twice a day, started from the morning of the second day of admission] based on conventional treatment) groups, based on their preference. General clinical data and peripheral blood samples were taken three times, in the morning before and 3 and 7 days after treatment. Fifteen adults with non-acute cerebral infarction matched for sex, age, and risk factors were recruited as controls; peripheral blood samples were only collected on the recruitment day. We used flow cytometry to detect the percentage of neutrophils and Real-Time PCR to detect the gene expression of interleukin (IL)-1ß in the peripheral blood samples. RESULTS: The percentage of neutrophils, pro-inflammatory neutrophils (IL-1ß high expression in flow cytometry), and IL-1ß mRNA expression increased after ACI (P = 0.01, P = 0.001, P < 0.001). The National Institutes of Health Stroke Scale (NIHSS) score of patients with ACI within one day of onset was positively correlated with the percentage of pro-inflammatory neutrophils (R = 0.618, P = 0.043). Pro-inflammatory neutrophils in the RIPostC group decreased compared with those in the conventional treatment group, with the most significant difference observed on Day 7 (P = 0.01). However, the percentage of neutrophils was not statistically different. IL-1ß mRNA expression decreased, with the most significant difference on Day 3 (P = 0.004). The NIHSS and Modified Rankin Scale scores for RIPostC decreased more significantly than for conventional treatment (P = 0.002, P = 0.019). CONCLUSION: More severe cerebral infarction was associated with a higher percentage of pro-inflammatory neutrophils. The neuroprotective effect of RIPostC may partly be exerted through gene regulation to reduce pro-inflammatory neutrophils.


Assuntos
Isquemia Encefálica , Pós-Condicionamento Isquêmico , Acidente Vascular Cerebral , Estados Unidos , Humanos , Pós-Condicionamento Isquêmico/efeitos adversos , Acidente Vascular Cerebral/etiologia , Isquemia Encefálica/etiologia , Infarto Cerebral/etiologia , RNA Mensageiro
7.
Front Neurol ; 14: 1149671, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37025208

RESUMO

The transient elevation of blood glucose produced following acute ischaemic stroke (AIS) has been described as stress-induced hyperglycaemia (SIH). SIH is common even in patients with AIS who have no previous diagnosis of diabetes mellitus. Elevated blood glucose levels during admission and hospitalization are strongly associated with enlarged infarct size and adverse prognosis in AIS patients. However, insulin-intensive glucose control therapy defined by admission blood glucose for SIH has not achieved the desired results, and new treatment ideas are urgently required. First, we explore the various definitions of SIH in the context of AIS and their predictive value in adverse outcomes. Then, we briefly discuss the mechanisms by which SIH arises, describing the dual effects of elevated glucose levels on the central nervous system. Finally, although preclinical studies support lowering blood glucose levels using insulin, the clinical outcomes of intensive glucose control are not promising. We discuss the reasons for this phenomenon.

8.
Curr Neuropharmacol ; 21(3): 621-650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35794770

RESUMO

As the first peripheral immune cells to enter the brain after ischemic stroke, neutrophils are important participants in stroke-related neuroinflammation. Neutrophils are quickly mobilized from the periphery in response to a stroke episode and cross the blood-brain barrier to reach the ischemic brain parenchyma. This process involves the mobilization and activation of neutrophils from peripheral immune organs (including the bone marrow and spleen), their chemotaxis in the peripheral blood, and their infiltration into the brain parenchyma (including disruption of the blood-brain barrier, inflammatory effects on brain tissue, and interactions with other immune cell types). In the past, it was believed that neutrophils aggravated brain injuries through the massive release of proteases, reactive oxygen species, pro-inflammatory factors, and extracellular structures known as neutrophil extracellular traps (NETs). With the failure of early clinical trials targeting neutrophils and uncovering their underlying heterogeneity, our view of their role in ischemic stroke has become more complex and multifaceted. As neutrophils can be divided into N1 and N2 phenotypes in tumors, neutrophils have also been found to have similar phenotypes after ischemic stroke, and play different roles in the development and prognosis of ischemic stroke. N1 neutrophils are dominant during the acute phase of stroke (within three days) and are responsible for the damage to neural structures via the aforementioned mechanisms. However, the proportion of N2 neutrophils gradually increases in later phases, and this has a beneficial effect through the release of anti-inflammatory factors and other neuroprotective mediators. Moreover, the N1 and N2 phenotypes are highly plastic and can be transformed into each other under certain conditions. The pronounced differences in their function and their high degree of plasticity make these neutrophil subpopulations promising targets for the treatment of ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Neutrófilos/metabolismo , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Acidente Vascular Cerebral/tratamento farmacológico , Encéfalo/patologia , Isquemia Encefálica/metabolismo
9.
Sci Total Environ ; 832: 155124, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35405227

RESUMO

Plastic additives affect the properties of plastics, which further determine the application range of plastics. However, most plastic additives have environmental friendliness or performance issues limiting their application. Hydrochar (HC) from waste biomass by hydrothermal carbonization has been proved to contain organic matter as function substances, like a binder, and is environment-friendly material. Currently, hydrochar as a plastic additive has not been previously reported. In this study, the HC/PBAT composites were produced by hydrochar blending with poly (butylene adipate-co-terephthalate) (PBAT) which is a biodegradable polymer. The hydrochar produced at different hydrothermal carbonization temperatures (180 °C, 210 °C, 240 °C, 270 °C, and 300 °C) and the addition of hydrochar (10 wt%, 20 wt%) were investigated. The results showed that the elastic modulus of the composites was increased by 27.4 MPa and 32.5 MPa compared with virgin PBAT while adding 10 wt% and 20 wt% hydrochar, respectively. Moreover, the stiffness of the composite was improved, and the balance of stiffness and toughness of the composites was effectively maintained when adding 10 wt% hydrochar treated at 300 °C. The elongation at break, tensile strength, and the elastic modulus of its composites were 630.8 ± 13.7%, 23.0 ± 0.4 MPa, and 100.5 ± 2.7 MPa, respectively. Furthermore, the crystallization temperature of the composites was increased after hydrochar was added into PBAT, and the maximum was 87.9 °C. It also means that hydrochar has a great nucleation effect during plastic processing. Therefore, hydrochar can be used as an environment-friendly additive to promote the performance of biodegradable plastic and promise to be applied in the field of biodegradable plastics.


Assuntos
Plásticos Biodegradáveis , Poliésteres/química , Polímeros , Temperatura , Resistência à Tração
10.
Anal Chem ; 94(4): 2189-2194, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35044176

RESUMO

The electrochemiluminescence (ECL) immunoassay with its visual and high-throughput detection has received considerable attention in the past decade. However, the development of a facile and cost-effective ECL device is still a great challenge. Herein, a single-electrode electrochemical system (SEES) for the visual and high-throughput ECL immunoassay was developed. The SEES was designed by attaching a plastic sticker with multiple holes onto a single carbon ink screen-printed electrode based on a resistance-induced potential difference. Due to its excellent properties of adsorption and bioaffinity, the carbon ink screen-printed electrode is applied to immobilize antibodies. When cardiac troponin I (cTnI), a specific biomarker of acute myocardial infarction, is present, it will be captured by the immobilized cTnI antibodies on the electrode surface, inhibiting electron transfer, resulting in a decrease of the ECL intensity of the luminol-H2O2 system. Using a smartphone as the detector, cTnI could be determined, ranging from 1 to 1000 ng mL-1, with a detection limit of 0.94 ng mL-1. The SEES based on the carbon ink screen-printed electrode is characterized by its high simplicity, cost effectiveness, and user-friendliness compared with conventional three-electrode systems and bipolar electrochemical systems using electrode arrays and shows superior advantages over other immunoassay strategies, with the elimination of multistep assembling and labeling processes. What is more, the fabricated SEES holds great potential in the point-of-care testing due to its tiny size and the combination of a smartphone detector.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Técnicas Eletroquímicas/métodos , Eletrodos , Peróxido de Hidrogênio , Imunoensaio/métodos , Limite de Detecção , Medições Luminescentes/métodos
11.
Curr Neuropharmacol ; 20(7): 1413-1426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34191698

RESUMO

The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota have also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.


Assuntos
Encefalomielite Autoimune Experimental , Microbioma Gastrointestinal , Esclerose Múltipla , Animais , Autoimunidade , Disbiose , Encefalomielite Autoimune Experimental/tratamento farmacológico , Humanos , Esclerose Múltipla/terapia
12.
Nat Sci Sleep ; 13: 1441-1448, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466044

RESUMO

Creutzfeldt-Jakob disease (CJD) subtypes are difficult to identify due to the heterogeneity of the clinical phenotype, and early accurate identification of sporadic CJD (sCJD) subtypes aids prognosis prediction. Currently, the diagnosis of sCJD subtypes is mainly based on brain tissue biopsy or autopsy. In this report, we present a case of confirmed sCJD initially presenting as insomnia. We described detailed information including clinical, electroencephalographic, polysomnographic, positron emission tomography-computed tomographic and other neuroimaging findings, cerebrospinal fluid biomarkers, skin tissue biopsy and whole blood PRNP gene sequencing in this patient. An extensive literature search was performed in order to better understand the diagnosis of various sCJD subtypes, particularly the thalamic form, sCJDMM2 (also known as sporadic fatal insomnia). Our study highlights sporadic fatal insomnia as a differential diagnosis of sCJD.

13.
Aging (Albany NY) ; 13(15): 19598-19613, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34343111

RESUMO

Ischemic stroke contributes to more than 80% of all strokes and has the four characteristics of high prevalence, high disability, high mortality, and high recurrence. Stroke is a preventable and controllable disease. In addition to controlling the primary disease, effective prevention and control measures need to be given to the occurrence and development of stroke. With the development and progress of modern treatment methods for ischemic stroke, the mortality and disability rate have decreased significantly. At present, the main treatment methods for ischemic stroke include thrombolysis, thrombus removal at the ultra-early stage, and treatment of improving collateral circulation in the acute phase. However, the ultra-early and early blood reperfusion involves reperfusion injury, which will cause secondary nerve damage, which is called cerebral ischemia/reperfusion injury (CIRI). Studies have found that autophagy is involved in the entire process of CIRI and can reduce the damage of CIRI. The mammalian target of Rapamycin (mTORC1) is the primary signal pathway regulating autophagy. And the mTORC1 inhibitor, Rapamycin, has been proved to exert neuroprotective effects in the ultra-early and early cerebral ischemia-reperfusion. Therefore, screening and designing mTORC1 inhibitors is very important to control reperfusion injury and reduce neuronal death and apoptosis. In this research, plenty of computer-assisted was applied to virtually screen and select potential mTORC1's inhibitors. We used Libdock to screen the structure and performed toxicity predictions, ADME (absorption, distribution, metabolism, excretion) to predict small molecules' pharmacological and toxicological properties. To assess the binding mechanism and affinity between the mTORC1 dimer and the ligand, molecular docking was performed. Then, the pharmacophore of small molecules in the docking conformation with the protein was supplemented by Schrodinger. Additionally, molecular dynamics simulations were conducted to assess if the ligand-receptor complex was stable in a natural environment. Furthermore, an experiment was performed to verify the inhibitory effect of compound 1 and compound 2 on mTOR protein. All in all, the study provides a hand of candidate drugs as well as pharmacological properties, which can play an essential role in mTORC1 inhibitors.


Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose , Autofagia/genética , Feminino , Humanos , AVC Isquêmico/patologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
ASN Neuro ; 13: 17590914211037505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34463559

RESUMO

Ischemic stroke is one of the main causes of high morbidity, mortality, and disability worldwide; however, the treatment methods are limited and do not always achieve satisfactory results. The pathogenesis of ischemic stroke is complex, defined by multiple mechanisms; among them, programmed death of neuronal cells plays a significant role. Ferroptosis is a novel type of regulated cell death characterized by iron redistribution or accumulation and increased lipid peroxidation in the membrane. Ferroptosis is implicated in many pathological conditions, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. In this review, we summarize current research findings on ferroptosis, including possible molecular mechanisms and therapeutic applications of ferroptosis regulators, with a focus on the involvement of ferroptosis in the pathogenesis and treatment of ischemic stroke. Understanding the role of ferroptosis in ischemic stroke will throw some light on the development of methods for diagnosis, treatment, and prevention of this devastating disease.


Assuntos
Isquemia Encefálica , Ferroptose , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Humanos , Peroxidação de Lipídeos , Acidente Vascular Cerebral/tratamento farmacológico
15.
Front Neurol ; 12: 679302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276539

RESUMO

Mitochondrial diseases are a group of common inherited disorders caused by mutations in nuclear DNA or mitochondrial DNA (mtDNA); the clinical phenotype of diseases caused by mutant mtDNA is challenging owing to heteroplasmy of mtDNA and may delay diagnosis and treatment. Herein, we report the case of an adult male who slowly developed epilepsy, ataxia, dystonia, impaired cognition, and hearing impairment over 14 years in the absence of clinical myopathy. His lactate level was normal. Brain computed tomography showed calcifications of the bilateral basal ganglia, thalamus, and cerebellar dentate nuclei. Magnetic resonance imaging revealed multiple lesions in the bilateral internal capsule and periventricular areas, which were hypointense on T1-weighted images and hyperintense on T2-weighted images. The first blood genetic test result was negative. Two years later, a muscle biopsy was performed. Succinate dehydrogenase (SDH) staining showed several ragged blue fibers and atypical strongly SDH-reactive vessels. Cytochrome C oxidase (COX) staining revealed abundant COX-deficient fibers. mtDNA testing of blood and muscle revealed a rare m.5549G>A mutation in the MT-TW gene. It was heteroplasmic, with 5.4% mutant mtDNA in the blood and 61.5% in the muscle. The patient was diagnosed with mitochondrial encephalomyopathy and treated with levetiracetam instead of valproate to reduce possible mitochondrial toxicity. After receiving anti-epileptic drugs and mitochondrial supplements, the patient remained clinically stable. For mitochondrial disease, when mutant mtDNA is not detected in blood, muscle biopsy should be performed in routine analysis, and it should be genetically tested, even if there are no manifestations of myopathy.

16.
Aging (Albany NY) ; 13(12): 16620-16636, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34170848

RESUMO

Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting dopamine receptors, Dopamine receptor agonists are a class of drugs similar in function and structure to dopamine and can directly act on dopamine receptors and activate it. Clinically, Dopamine receptor agonist drugs have achieved significant therapeutic effects on prolactinoma and Parkinson's Disease. In the study, we virtually screened a series of potential effective agonists of Dopamine receptor by computer techniques. Firstly, we used the Molecular Docking (LibDock) step to screen out some molecules that can dock well with the protein. Then, analysis of toxicity prediction and ADME (adsorption, distribution, metabolism and excretion) were carried out. More precise molecular docking (CDOCKER) and 3-Dimensional Quantitative Structure-Activity Relationship Modeling Study(3D-QSAR) pharmacophore generation were implemented to research and explore these compounds' binding mechanism with Dopamine receptor. Last but not least, to assess compound's binding stabilities, we carried out a molecular dynamic analysis. As the results show, two compounds (ZINC000008860530 and ZINC000004096987) from the small molecule database (ZINC database) were potential effective agonists of Dopamine receptor. These two compounds can combine with Dopamine receptor with higher affinity and proved to be no toxic. The cell experiment showed that two compounds could inhibit the proliferation and PRL secretion of MMQ cells (pituitary tumor cells). Thus, this study provided valuable information about Dopamine receptor agonist-based drug discovery. So, this study will benefit patients with prolactinoma and Parkinson's disease a lot.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacologia , Agonistas de Dopamina/química , Agonistas de Dopamina/farmacologia , Simulação de Acoplamento Molecular , Receptores Dopaminérgicos/química , Produtos Biológicos/análise , Produtos Biológicos/toxicidade , Bromocriptina/química , Bromocriptina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Agonistas de Dopamina/análise , Agonistas de Dopamina/toxicidade , Avaliação Pré-Clínica de Medicamentos , Humanos , Ligação de Hidrogênio , Ligantes , Simulação de Dinâmica Molecular , Prolactina/metabolismo
17.
Front Neurol ; 12: 546481, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025545

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is a relatively rare clinical disease, characterized by reversible subcortical vasogenic edema. Here, we present the first reported case of PRES induced by anlotinib, a multi-target tyrosine kinase inhibitor. A 56-year-old female patient with lung adenocarcinoma and bone metastasis experienced hypertension and mental confusion when she received anti-angiogenesis treatment. PRES was diagnosed after magnetic resonance of the patient's brain revealed hyperintensities bilaterally around the cerebellum, pons, fronto-parieto-occipital areas, and corona radiate. Diffusion-weighted imaging showed hyperintensities bilaterally in the parieto-occipital cortical regions. Subsequently, the patient was diagnosed with PRES, and remission was achieved with anti-hypertensive drugs. Six cases of rare adverse effects induced by anlotinib were reviewed in the literature. Since anlotinib has been widely applied as a novel third-line treatment in patients with non-small-cell lung cancer, the association between PRES and anlotinib would benefit neurologists and oncologists in future diagnoses and treatment.

18.
J Int Med Res ; 49(5): 3000605211016815, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34057834

RESUMO

A 58-year-old male vegetarian presented with progressive numbness and weakness in the lower extremities. Laboratory examinations showed reduced vitamin B12 level with megaloblastic anaemia. Spinal magnetic resonance imaging (MRI) revealed hyperintensity within the posterior and lateral columns on T2-weighted imaging. The diagnosis of subacute combined degeneration (SCD) of the spinal cord was established. Unexpectedly, the patient developed transitory syncope on the second day after hospitalization. The diagnostic computed tomography pulmonary angiography (CTPA) confirmed multiple small pulmonary emboli. An isolated significantly elevated level of homocysteine (117.1 µmol/l) was documented when screening for hypercoagulable markers. Except for a long-term vegetarian diet, no other risk factors for hyperhomocysteinaemia (such as a family history of homocysteinuria) was found. The severity of the hyperhomocysteinaemia found in this current patient was unusual for patients with an insufficient intake of vitamin B12. In SCD patients, elevated homocysteine may increase the risk of thrombosis, which may exacerbate existing problems. Knowing the risk factors should help physicians choose appropriate diagnostic and therapeutic strategies.


Assuntos
Embolia Pulmonar , Degeneração Combinada Subaguda , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Degeneração Combinada Subaguda/complicações , Degeneração Combinada Subaguda/diagnóstico por imagem , Vitamina B 12
19.
Front Pharmacol ; 12: 608130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995011

RESUMO

Guillain-Barré syndrome (GBS) is an acute polyneuropathy mostly characterized by acute flaccid paralysis with or without sensory/autonomous nerve dysfunction. Current immuno therapies including intravenous immunoglobulin (IVIg), plasma exchange (PE), and newly developed biological drugs benefit patients by alleviating hyperreactive immune responses. Up to 30% of patients develop respiratory failure during hospitalization and require mechanical ventilation and intensive care. Immunotherapies, mechanical ventilation, supportive care, and complication management during the intensive care unit (ICU) stay are equally emphasized. The most important aspect of intensive care and treatment of severe GBS, that is, mechanical ventilation, has been extensively reviewed elsewhere. In contrast to immunotherapies, care and treatment of GBS in the ICU setting are largely empirical. In this review, we intend to stress the importance of intensive care and treatment, other than mechanical ventilation in patients with severe GBS. We summarize the up-to-date knowledge of pharmacological therapies and ICU management of patients with severe GBS. We aim to answer some key clinical questions related to the management of severe GBS patients including but not limited to: Is IVIg better than PE or vice versa? Whether combinations of immune therapies benefit more? How about the emerging therapies promising for GBS? When to perform tracheal intubation or tracheostomy? How to provide multidisciplinary supportive care for severe cases? How to avert life-threatening complications in severe cases?

20.
Ann Palliat Med ; 10(7): 8448-8453, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33894706

RESUMO

Streptococcus suis (S. suis), a gram-positive facultative anaerobe, has emerged as a zoonotic pathogen of suppurative infections in various human organs. Never reported is human primary ventriculitis caused by S. suis. A 70-year-old Chinese woman with a history of eating undercooked pork tongue was admitted to our hospital due to vomiting, headache and high fever. Brain magnetic resonance imaging (MRI) revealed intraventricular empyema and hydrocephalus, while cerebrospinal fluid (CSF) analysis showed purulent changes. S. suis was cultured in the CSF and blood samples of the patient, and confirmed as serotype 2 by real-time polymerase chain reaction (PCR). Therefore, the diagnosis of primary ventriculitis caused by S. suis was established. She was treated with intravenous (IV) meropenem for six weeks. To solve hydrocephalus, external ventricular drain (EVD) was performed, followed by ventriculoperitoneal shunt. Finally, the patient achieved a good outcome after a 6-month follow-up. S. suis is a rare pathogen in northern China but can cause severe infection and complications. S. suis infection should be considered when a patient with bacterial infection has a history of eating undercooked pork. MRI can help detect ventriculitis. It is worth noting that rapid and prolongated administration of IV antibiotics and timely neurosurgical intervention can achieve desirable outcomes.


Assuntos
Ventriculite Cerebral , Infecções Estreptocócicas , Streptococcus suis , Idoso , Antibacterianos/uso terapêutico , Ventriculite Cerebral/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico
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