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1.
Molecules ; 29(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38611748

RESUMO

Stem cell-derived exosomes (SC-Exos) are used as a source of regenerative medicine, but certain limitations hinder their uses. The effect of hydrolyzed collagen oligopeptides (HCOPs), a functional ingredient of SC-Exos is not widely known to the general public. We herein evaluated the combined anti-aging effects of HCOPs and exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exos) using a senescence model established on human skin fibroblasts (HSFs). This study discovered that cells treated with HucMSC-Exos + HCOPs enhanced their proliferative and migratory capabilities; reduced both reactive oxygen species production and senescence-associated ß-galactosidase activity; augmented type I and type III collagen expression; attenuated the expression of matrix-degrading metalloproteinases (MMP-1, MMP-3, and MMP-9), interleukin 1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α); and decreased the expression of p16, p21, and p53 as compared with the cells treated with HucMSC-Exos or HCOPs alone. These results suggest a possible strategy for enhancing the skin anti-aging ability of HucMSC-Exos with HCOPs.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Humanos , Fibroblastos , Envelhecimento , Colágeno Tipo III , Cordão Umbilical
2.
Bull Environ Contam Toxicol ; 112(4): 62, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38615308

RESUMO

Acetamiprid is a novel nicotinic pesticide widely used in modern agriculture because of its low toxicity and specific biological target properties. The objective of this study was to understand the photolysis pattern of acetamiprid in the water column and elucidate its degradation products and mechanism. It was observed that acetamiprid exhibited different photolysis rates under different light source conditions in pure water, with ultraviolet > fluorescence > sunlight; furthermore, its photolysis half-life ranged from 17.3 to 28.6 h. In addition, alkaline conditions (pH 9.0) accelerated its photolysis rate, which increased with pH. Using gas chromatography-mass spectrometry, five direct photolysis products generated during the exposure of acetamiprid to pure water were successfully separated and identified. The molecular structure of acetamiprid was further analyzed using density functional theory, and the active photodegradation sites of acetamiprid were predicted. The mechanism of the photolytic transformation of acetamiprid in water was mainly related to hydroxyl substitution and oxidation. Based on these findings, a comprehensive transformation pathway for acetamiprid was proposed.


Assuntos
Neonicotinoides , Praguicidas , Nicotina , Agricultura , Água
3.
Front Mol Neurosci ; 17: 1379726, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638604

RESUMO

Netrin-1 was initially discovered as a neuronal growth cue for axonal guidance, and its functions have later been identified in inflammation, tumorigenesis, neurodegeneration, and other disorders. We have recently found its alterations in the brains with Alzheimer's disease, which might provide important clues to the mechanisms of some unique pathologies. To provide better understanding of this promising molecule, we here summarize research progresses in genetics, pathology, biochemistry, cell biology and other studies of Netrin-1 about its mechanistic roles and biomarker potentials with an emphasis on clinical neurodegenerative disorders in order to expand understanding of this promising molecular player in human diseases.

4.
Heliyon ; 10(8): e28863, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38638974

RESUMO

Background: As a scaffold protein, calcium/calmodulin-dependent serine protein kinase (CASK) has been extensively studied in a variety of tissues throughout the body. The Cask gene is ubiquitous in several tissues, such as the neurons, islets, heart, kidneys and sperm, and is mostly localised in the cytoplasm adjacent to the basement membrane. CASK binds to a variety of proteins through its domains to exerting its biological activity. Scope of review: Here, we discuss the role of CASK in multiple tissues throughout the body. The role of different CASK domains in regulating neuronal development, neurotransmitter release and synaptic vesicle secretion was emphasised; the regulatory mechanism of CASK on the function of pancreatic islet ß cells was analysed; the role of CASK in cardiac physiology, kidney and sperm development was discussed; and the role of CASK in different tumours was compared. Finally, we clarify the importance of the Cask gene in the body, and how deletion or mutation of the Cask gene can have adverse consequences. Major conclusions: CASK is a conserved gene with similar roles in various tissues. The function of the Cask gene in the nervous system is mainly involved in the development of the nervous system and the release of neurotransmitters. In the endocrine system, an involvement of CASK has been reported in the process of insulin vesicle transport. CASK is also involved in cardiomyocyte ion channel regulation, kidney and sperm development, and tumour proliferation. CASK is an indispensable gene for the whole body, and CASK mutations can cause foetal malformations or death at birth. In this review, we summarise the biological functions and pathological mechanisms of CASK in various systems, thereby providing a basis for further in-depth studies of CASK functions.

5.
Clin Rheumatol ; 43(5): 1623-1634, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38436769

RESUMO

OBJECTIVE: To construct a molecular immune map of patients with systemic sclerosis (SSc) by mass flow cytometry, and compare the number and molecular expression of double-negative T (DNT) cell subsets between patients and healthy controls (HC). METHODS: Peripheral blood mononuclear cells (PBMCs) were extracted from the peripheral blood of 17 SSc patients and 9 HC. A 42-channel panel was set up to perform mass cytometry by time of flight (CyTOF) analysis for DNT subgroups. Flow cytometry was used to validate subpopulation functions. The clinical data of patients were collected for correlation analysis. RESULTS: Compared with HC, the number of total DNT cells decreased in SSc patients. Six DNT subsets were obtained from CyTOF analysis, in which the proportion of cluster1 increased, while the proportion of cluster3 decreased. Further analysis revealed that cluster1 was characterized by high expression of CD28 and CCR7, and cluster3 was characterized by high expression of CD28 and CCR5. After in vitro stimulation, cluster1 secreted more IL-4 and cluster3 secreted more IL-10 in SSc patients compared to HC. Clinical correlation analysis suggested that cluster1 may play a pathogenic role while cluster3 may play a protective role in SSc. ROC curve analysis further revealed that cluster3 may be a potential indicator for determining disease activity in SSc patients. CONCLUSION: We found a new CCR5+CD28+ DNT cell subset, which played a protective role in the pathogenesis of SSc. Key Points • The number of DNT cells decreased in SSc patients' peripheral blood. • DNT cells do not infiltrate in the skin but secrete cytokines to participate in the pathogenesis of SSc. • A CCR5+CD28+ DNT cell population may play a protective role in SSc.


Assuntos
Leucócitos Mononucleares , Escleroderma Sistêmico , Humanos , Leucócitos Mononucleares/metabolismo , Antígenos CD28 , Citocinas/metabolismo , Subpopulações de Linfócitos T
6.
J Chem Inf Model ; 64(8): 3105-3113, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516950

RESUMO

Molecular property prediction is a fundamental task of drug discovery. With the rapid development of deep learning, computational approaches for predicting molecular properties are experiencing increasing popularity. However, these existing methods often ignore the 3D information on molecules, which is critical in molecular representation learning. In the past few years, several self-supervised learning (SSL) approaches have been proposed to exploit the geometric information by using pre-training on 3D molecular graphs and fine-tuning on 2D molecular graphs. Most of these approaches are based on the global geometry of molecules, and there is still a challenge in capturing the local structure and local interpretability. To this end, we propose local geometry-guided graph attention (LGGA), which integrates local geometry into the attention mechanism and message-passing of graph neural networks (GNNs). LGGA introduces a novel method to model molecules, enhancing the model's ability to capture intricate local structural details. Experiments on various data sets demonstrate that the integration of local geometry has a significant impact on the improved results, and our model outperforms the state-of-the-art methods for molecular property prediction, establishing its potential as a promising tool in drug discovery and related fields.


Assuntos
Descoberta de Drogas , Redes Neurais de Computação , Descoberta de Drogas/métodos , Modelos Moleculares , Aprendizado Profundo
7.
J Am Heart Assoc ; 13(5): e032840, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38420847

RESUMO

BACKGROUND: Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months. This study aimed to identify potential biomarkers for predicting stroke recurrence. METHODS AND RESULTS: We conducted a nested case-control study using a hospital-based cohort from the Third China National Stroke Registry selecting 214 age- and sex-matched patients with ischemic stroke with hypertension and no history of diabetes or heart disease. Using data-independent acquisition for discovery and multiple reaction monitoring for quantitative validation, we identified 26 differentially expressed proteins in large-artery atherosclerosis (Causative Classification of Ischemic Stroke [CCS]1), 16 in small-artery occlusion (CCS3), and 25 in undetermined causes (CCS5) among patients with recurrent stroke. In the CCS1 and CCS3 subgroups, differentially expressed proteins were associated with platelet aggregation, neuronal death/cerebroprotection, and immune response, whereas differentially expressed proteins in the CCS5 subgroup were linked to altered metabolic functions. Validated recurrence predictors included proteins associated with neutrophil activity and vascular inflammation (TAGLN2 [transgelin 2], ITGAM [integrin subunit α M]/TAGLN2 ratio, ITGAM/MYL9 [myosin light chain 9] ratio, TAGLN2/RSU1 [Ras suppressor protein 1] ratio) in the CCS3 subgroup and proteins associated with endothelial plasticity and blood-brain barrier integrity (ITGAM/MYL9 ratio and COL1A2 [collagen type I α 2 chain]/MYL9 ratio) in the CCS3 and CCS5 subgroups, respectively. CONCLUSIONS: These findings provide a foundation for developing a blood-based biomarker panel, using causative classifications, which may be used in routine clinical practice to predict stroke recurrence.


Assuntos
Aterosclerose , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/etiologia , AVC Isquêmico/complicações , Estudos de Casos e Controles , Acidente Vascular Cerebral/etiologia , Aterosclerose/complicações , Biomarcadores , Recidiva , Fatores de Risco , Fatores de Transcrição
8.
Environ Sci Pollut Res Int ; 31(14): 21668-21686, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38393572

RESUMO

China, the world's largest consumer and producer of pork in the world, is attracting increasing attention due to the environmental impacts of its pig production. Previous studies seldom comprehensively compare the environmental impacts of the pig production system with different models, resulting in different intensities of environmental impacts. We aim to comprehensively evaluate Chinese pig production with different breeding models and explore a more sustainable way for pig production. We use life cycle assessment (LCA) to evaluate and compare environmental impacts of pig production system with four main breeding models in China from 1998 to 2020: domestic breeding, small-scale breeding, medium-scale breeding, and large-scale breeding. The life cycle encompasses fertilizer production, feed production, feed processing, pig raising, waste treatment, and slaughtering. The impact categories including energy consumption (EN), global warming (GWP), acidification (AP), eutrophication (EU), water use (WD), and land occupation (LO) are expressed with "100 kg live weight of fattening pig at farm gate." The results show that driven by governmental support, growing meat demand, and cost advantage, the scale breeding especially large-scale breeding simultaneously yielded greater net economic benefit and less environmental impact compared to other breeding models especially the domestic breeding. Due to mineral fertilizer application, feed production contributed over 50% of the total environmental impacts. Notably, the composition of feeds exerted significant influence on the environmental impacts arising from fertilizer production and feed processing. Furthermore, attributable to the substantial use of electricity and heat, as well as the concomitant emissions, pig raising contributed the largest GWP, while ranking second in terms of AP and EU. Notably, waste management constituted the third-largest EU, AP, and WD. In addition to promote scale breeding, we put forth several sustainable measures encompassing feed composition, cultivation practices, fertilizer utilization, and waste management for consideration.


Assuntos
Conservação dos Recursos Naturais , Fertilizantes , Animais , Suínos , Fazendas , Aquecimento Global , China
9.
Front Pharmacol ; 15: 1329636, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323081

RESUMO

Albumin is derived from human or animal blood, and its ability to bind to a large number of endogenous or exogenous biomolecules makes it an ideal drug carrier. As a result, albumin-based drug delivery systems are increasingly being studied. With these in mind, detailed studies of the transport mechanism of albumin-based drug carriers are particularly important. As albumin receptors, glycoprotein 60 (GP60) and secreted protein acidic and rich in cysteine (SPARC) play a crucial role in the delivery of albumin-based drug carriers. GP60 is expressed on vascular endothelial cells and enables albumin to cross the vascular endothelial cell layer, and SPARC is overexpressed in many types of tumor cells, while it is minimally expressed in normal tissue cells. Thus, this review supplements existing articles by detailing the research history and specific biological functions of GP60 or SPARC and research advances in the delivery of antitumor drugs using albumin as a carrier. Meanwhile, the deficiencies and future perspectives in the study of the interaction of albumin with GP60 and SPARC are also pointed out.

10.
Sci Transl Med ; 16(736): eadg5116, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416841

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)-rich ADEVs in patients with AQP4-Abs-positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE130-149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor-related protein 1 (LRP1) could block the restorative effects of APOE130-149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE-/- mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.


Assuntos
Neuromielite Óptica , Humanos , Animais , Camundongos , Astrócitos/metabolismo , Aquaporina 4 , Proteômica , Apolipoproteínas E , Autoanticorpos
12.
Aging (Albany NY) ; 16(1): 665-684, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217543

RESUMO

Anoikis is essential for the progression of many malignant tumors. However, the understanding of anoikis' roles in osteosarcoma remains scarce. This study conducted an extensive bioinformatics analysis to identify anoikis-related genes (ARGs), developed ARGs modeles for predicting OS and RFS, and evaluated the effect of these ARGs on osteosarcoma cell migration and invasion. The GSE16088 and GSE28425 datasets provided the differentially expressed genes (DEGs). The prognostic significance and functions of these DEGs were systematically investigated using several bioinformatics techniques. Transwell assays were conducted to determine the effect of OGT on osteosarcoma cell migration and invasion. Seven genes were identified as hub genes, including FN1, CD44, HRAS, TP53, PPARG, CTNNB1, and VEGFA, while 71 ARGs were identified as DEGs. Four ARGs-BRMS, COL4A2, FGF2, and OGT-were used to develop an RFS-predicting model, whereas seven ARGs-CD24, FASN, MMP2, EIF2AK3, ID2, PPARG, and PIK3R3-were used to develop an OS-predicting model in patients with osteosarcoma. In both the training and validation cohorts, high-risk group patients had significantly shorter OS and RFS duration than low-risk group patients. Furthermore, using the aforementioned ARGs, we developed clinically applicable nomograms for OS and RFS prediction. The proportion of tumor-infiltrating immune cells was significantly linked to risk scores. In vitro experiments revealed that knocking down OGT significantly inhibited the ability of MG63 and U2OS cells to invade and migrate. ARG-based gene signatures reliably predicted RFS and OS in osteosarcoma, and OGT showed promise as a potential biomarker. These findings contribute to a better understanding of ARGs' prognostic roles in osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Anoikis/genética , PPAR gama , Osteossarcoma/genética , Bioensaio , Neoplasias Ósseas/genética , Prognóstico , Fosfatidilinositol 3-Quinases
13.
Adv Mater ; 36(1): e2305841, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37947249

RESUMO

Sb2 S3 is a promising environmentally friendly semiconductor for high performance solar cells. But, like many other polycrystalline materials, Sb2 S3 is limited by nonradiative recombination and carrier scattering by grain boundaries (GBs). This work shows how the GB density in Sb2 S3 films can be significantly reduced from 1068 ± 40 to 327 ± 23 nm µm-2 by incorporating an appropriate amount of Ce3+ into the precursor solution for Sb2 S3 deposition. Through extensive characterization of structural, morphological, and optoelectronic properties, complemented with computations, it is revealed that a critical factor is the formation of an ultrathin Ce2 S3 layer at the CdS/Sb2 S3 interface, which can reduce the interfacial energy and increase the adhesion work between Sb2 S3 and the substrate to encourage heterogeneous nucleation of Sb2 S3 , as well as promote lateral grain growth. Through reductions in nonradiative recombination at GBs and/or the CdS/Sb2 S3 heterointerface, as well as improved charge-carrier transport properties at the heterojunction, this work achieves high performance Sb2 S3 solar cells with a power conversion efficiency reaching 7.66%. An impressive open-circuit voltage (VOC ) of 796 mV is achieved, which is the highest reported thus far for Sb2 S3 solar cells. This work provides a strategy to simultaneously regulate the nucleation and growth of Sb2 S3 absorber films for enhanced device performance.

14.
Adv Healthc Mater ; 13(5): e2302192, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38018632

RESUMO

Corneal neovascularization (CNV) is one of the leading causes of blindness in the world. In clinical practice; however, it remains a challenge to achieve a noninvasive and safe treatment. Herein, a biocompatible shell with excellent antioxidant and antivascularity is prepared by co-assembly of epigallocatechin gallate/gallic acid and Cu (II). After loading glucose oxidase (GOx) inside, the shell is modified with dimeric DPA-Zn for codelivering vascular endothelial growth factor (VEGF) small interfering RNA (VEGF-siRNA). Meanwhile, the Arg-Gly-Asp peptide (RGD) peptide-engineered cell membranes coating improves angiogenesis-targeting and is biocompatible for the multifunctional nanomedicine (CEGs/RGD). After eye drops administration, CEGs/RGD targets enrichment in neovascularization and CEGs NPs enter cells. Then, the inner GOx consumes glucose with a decrease in local pH, which in turn leads to the release of EGCE and VEGF-siRNA. As a result, the nanomedicines significantly reduce angiogenesis and inhibit CNV formation through synergistic effect of antioxidant and antivascular via down-regulation of cluster of differentiation 31 and VEGF. The nanomedicine represents a safe and efficient CNV treatment through the combined effect of antioxidant/gene, which provides important theoretical and clinical significance.


Assuntos
Neovascularização da Córnea , Humanos , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , RNA Interferente Pequeno/farmacologia , Oligopeptídeos/farmacologia
15.
Int Immunopharmacol ; 126: 111256, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37992447

RESUMO

The inflammatory response runs through the whole pathogenesis of systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSC) have exhibited a positive therapeutic effect on SLE. This study aimed to ascertain the pathogenic role of inflammasome activation in SLE and whether MSC alleviate SLE by suppressing it. The results showed that the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome was activated in macrophages from MRL/lpr mice and patients with SLE, correlating with disease activity. After MSC transplantation, the disease severity in MRL/lpr mice was alleviated, and NLRP3 inflammasome activation was inhibited with decreased levels of NLRP3 and caspase-1 in macrophages. Furthermore, lower serum levels of interleukin (IL)-1ß and IL-18 were observed in patients with SLE who underwent MSC transplantation. In vitro and in vivo studies indicated that MSC suppressed NLRP3 inflammasome activation by inhibiting Pim-1 expression. The findings provide an updated view of inflammasome signaling in SLE. Additionally, MSC ameliorated SLE by inhibiting NLRP3 inflammasome activation, implying a possible molecular mechanism for the clinical application of MSC and a potential therapeutic target in patients with SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Células-Tronco Mesenquimais , Animais , Humanos , Camundongos , Inflamassomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos MRL lpr , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Proto-Oncogênicas c-pim-1
16.
Oral Dis ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129747

RESUMO

OBJECTIVE: To investigate the genetic causes of 22 patients with clinically high suspicion of X-linked hypohidrotic ectodermal dysplasia from 20 unrelated Chinese families, expand the spectrum of ectodysplasin-A mutations, and provide more evidence for variants of uncertain significance. SUBJECTS AND METHODS: Whole-exome sequencing was performed and potentially pathogenic variants were verified by Sanger sequencing. Western blotting, real-time PCR and immunofluorescence analyses were performed to investigate the preliminary functions of the candidate variants. RESULTS: Nineteen ectodysplasin-A variants were identified, six of which were not previously reported. Among these variants, we identified a patient who carried two mutations in ectodysplasin-A and exhibited more severe phenotypes. Additionally, mutant protein expression levels decreased, whereas mRNA transcription levels increased. Cellular sublocalisation of the variants located in the tumour necrosis factor homologous domain showed that the proteins accumulated in the nucleus, whereas wild-type proteins remained in the cell membrane. A rare indel variant and two classical splicing variants that lead to exon 7 skipping were detected. CONCLUSIONS: This study provides definitive diagnoses for 20 families with suspected X-linked hypohidrotic ectodermal dysplasia and additional information on clinical heterogeneity and genotype-phenotype relationships.

17.
Clin Lab ; 69(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37948492

RESUMO

BACKGROUND: Brain injury triggers neuroaxonal injury and neural death, that leads to the development of secondary sequelae. Throughout this process, brain injury factors released into circulation via the injured neurovascular unit are important prognostic parameters. Plasma NfL, NfH, MCP-1, and MMP-9 have been identified as potential indicators in this regard. METHODS: Using a microfluidic ELISA platform, we measured plasma from 273 healthy subjects that underwent quantifications of NfL, NfH, MCP-1, and MMP-9 levels. We investigated the possible associations between biomarkers and basic demographics. RESULTS: The median concentration of plasma NfL was 10.40 (IQR = 6.73 - 16.60) pg/mL, NfH was 70.70 (IQR = 39.75 - 125.50) pg/mL, MCP-1 was 191.0 (IQR = 162.0 - 237.5) pg/mL, and MMP-9 was 169,255 (IQR = 107,657 - 231,276) pg/mL. Among all four biomarkers, plasma NfL and NfH levels were positively correlated with age (r = 0.557, p < 0.001, r = 0.364, p = 0.003). NfL was also correlated with NfH (r = 0.391, p = 0.002). CONCLUSIONS: These data provide a basis for the potential application of a brain-injury biomarker panel in routine clinical practice. It lays a significant foundation in supporting circulating CNS-biomarkers as noninvasive biomarkers for neurological disorders.


Assuntos
Lesões Encefálicas , Metaloproteinase 9 da Matriz , Humanos , Valores de Referência , População do Leste Asiático , Biomarcadores
18.
CNS Neurosci Ther ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990436

RESUMO

BACKGROUND: Despite extensive work to identify diagnostic plasma markers for Parkinson's disease (PD), there are still no accepted and validated surrogate biomarkers. Mitophagy-associated proteins (MAPs), including PTEN-induced putative kinase 1 (PINK1), Parkin, phosphoglycerate mutase 5 (PGAM5), BCL2 interacting protein 3 (BNIP3), and phosphorylated-TBK1 (p-TBK1), are, to our best knowledge, not well studied as a panel of biomarkers of neurodegeneration in PD. METHODS: The study population comprised 116 age-matched controls (HC), 179 PD patients, alongside and 90 PD syndromes (PDs) divided between two cohorts: (i) the modeling cohort (cohort 1), including 150 PD, 97 HC, and 80 PDs; and (ii) the validated cohort (cohort 2), including 29 PD, 19 HC, and 10 PDs. RESULTS: MAPs are elevated in the plasma of PD patients. PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p-TBK1. Moreover, the area under the curve (AUC) values of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from HC, but the MAPs make it hard to differentiate PD from PDs. In addition, there are higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-synuclein (+) subjects than in A-synuclein (-) subjects. CONCLUSIONS: These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful diagnostic biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prognosis.

19.
RSC Adv ; 13(48): 33911-33917, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38020029

RESUMO

The investigation of the properties of aggregate materials is highly interesting because the process of aggregation can result in the disappearance of original properties and the emergence of new ones. Here, a novel fluorescent material (TPEIP), which synergistically combines aggregation-induced emission (AIE) and aggregation caused quenching (ACQ) moieties, was first synthesized by the cyclization reaction of 2,3-diamino-phenazine with 4-tetraphenylenthenealdehyde. We controlled the degree of aggregation of TPEIP to shed light on the impact of the aggregation on the excited state dynamics. TPEIP aggregation realized control over the Intersystem Crossing (ISC) rates and, in turn, the suppression of triplet excited states in MeOH, EtOH or via the simple addition of water to TPEIP solutions in DMSO. From global target analysis, the time scale was 966.2 ps for ISC for TPEIP in DMSO, but it was 860 ps in the case of TPEIP solutions featuring 5% water. The dynamics of TPEIP excited states undergo significant changes as the degree of aggregation increases. Notably, the lifetime of singlet excited states decreases, and there was a gradual diminishment in triplet states.

20.
Ann Indian Acad Neurol ; 26(5): 742-748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022444

RESUMO

Objective: In patients with post-stroke oropharyngeal dysphagia (PSOD), classical dysphagia therapy (CDT) continues to provide unsatisfactory outcomes and makes it challenging for them to remove the nasal feeding tube. Increasing bolus viscosity helps prevent aspiration in PSOD. However, conventional starch thickeners enhance post-digestion residue. This study aims to evaluate the efficacy of swallow training with xanthan gum-based thickener (XGT) (Softia G, NUTRI Co., Ltd., Yokkaichi, Japan) additional to CDT in Chinese PSOD patients with a nasogastric tube when compared to CDT alone. Methods: Patients with PSOD who had a nasogastric tube were randomly assigned to either the experimental group (E-group) or the control group (C-group) in this randomized controlled, single-blind, parallel-group study. Both groups received CDT for 4 weeks. The E-group cases received additional swallow training with a Softia G-prepared hydrogel training material. The Functional Oral Intake Scale (FOIS) and modified volume-viscosity swallow test (M-VVST) for swallowing safety and efficacy according to adjusted Chinese dietary habits were administered before and after treatment. Post-training, both groups' nasogastric tube removal rates were calculated. Results: One hundred sixty-seven participants (E-group: 82 and C-group: 85) completed the study. The E-group's median score of FOIS improved significantly than the C-group after training (median = 5 vs. 3, P < 0.001). The incidence of coughing, voice changes, oxygen desaturation of 3% or more, pharyngeal residue and piecemeal deglutition in the E-group was significantly lower than that in the C-group (P < 0.05). The E-group had 100% nasogastric tube removal, while the C-group had 28.24% (P < 0.001). Conclusion: Swallow training with XGT Softia G in addition to CDT can promote swallowing safety and efficacy in Chinese patients with PSOD more effectively than CDT alone.

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