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1.
Cell ; 155(5): 997-1007, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24267886

RESUMO

Autism spectrum disorder (ASD) is a complex developmental syndrome of unknown etiology. Recent studies employing exome- and genome-wide sequencing have identified nine high-confidence ASD (hcASD) genes. Working from the hypothesis that ASD-associated mutations in these biologically pleiotropic genes will disrupt intersecting developmental processes to contribute to a common phenotype, we have attempted to identify time periods, brain regions, and cell types in which these genes converge. We have constructed coexpression networks based on the hcASD "seed" genes, leveraging a rich expression data set encompassing multiple human brain regions across human development and into adulthood. By assessing enrichment of an independent set of probable ASD (pASD) genes, derived from the same sequencing studies, we demonstrate a key point of convergence in midfetal layer 5/6 cortical projection neurons. This approach informs when, where, and in what cell types mutations in these specific genes may be productively studied to clarify ASD pathophysiology.


Assuntos
Encéfalo/metabolismo , Transtornos Globais do Desenvolvimento Infantil/genética , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Animais , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Transtornos Globais do Desenvolvimento Infantil/patologia , Exoma , Feminino , Feto/metabolismo , Feto/patologia , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos , Mutação , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Análise de Sequência de DNA
2.
Bioessays ; 46(7): e2400047, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38769699

RESUMO

Recent insights reveal the significant role of TRPV3 in warmth sensation. A novel finding elucidated how thermosensation is affected by TRPV3 membrane abundance that is modulated by the transmembrane protein TMEM79. TRPV3 is a warmth-sensitive ion channel predominantly expressed in epithelial cells, particularly skin keratinocytes. Multiple studies investigated the roles of TRPV3 in cutaneous physiology and pathophysiology. TRPV3 activation by innocuous warm temperatures in keratinocytes highlights its significance in temperature sensation, but whether TRPV3 directly contributes to warmth sensations in vivo remains controversial. This review explores the electrophysiological and structural properties of TRPV3 and how modulators affect its intricate regulatory mechanisms. Moreover, we discuss the multifaceted involvement of TRPV3 in skin physiology and pathology, including barrier formation, hair growth, inflammation, and itching. Finally, we examine the potential of TRPV3 as a therapeutic target for skin diseases and highlight its diverse role in maintaining skin homeostasis.


Assuntos
Homeostase , Queratinócitos , Pele , Canais de Cátion TRPV , Canais de Cátion TRPV/metabolismo , Humanos , Animais , Pele/metabolismo , Queratinócitos/metabolismo , Sensação Térmica/fisiologia , Dermatopatias/metabolismo , Dermatopatias/tratamento farmacológico
3.
Proc Natl Acad Sci U S A ; 119(34): e2205518119, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969737

RESUMO

Testing the significance of predictors in a regression model is one of the most important topics in statistics. This problem is especially difficult without any parametric assumptions on the data. This paper aims to test the null hypothesis that given confounding variables Z, X does not significantly contribute to the prediction of Y under the model-free setting, where X and Z are possibly high dimensional. We propose a general framework that first fits nonparametric machine learning regression algorithms on [Formula: see text] and [Formula: see text], then compares the prediction power of the two models. The proposed method allows us to leverage the strength of the most powerful regression algorithms developed in the modern machine learning community. The P value for the test can be easily obtained by permutation. In simulations, we find that the proposed method is more powerful compared to existing methods. The proposed method allows us to draw biologically meaningful conclusions from two gene expression data analyses without strong distributional assumptions: 1) testing the prediction power of sequencing RNA for the proteins in cellular indexing of transcriptomes and epitopes by sequencing data and 2) identification of spatially variable genes in spatially resolved transcriptomics data.


Assuntos
Genômica , Aprendizado de Máquina , Algoritmos , Análise de Regressão , Transcriptoma
4.
Biometrics ; 80(1)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38465983

RESUMO

In genomics studies, the investigation of gene relationships often brings important biological insights. Currently, the large heterogeneous datasets impose new challenges for statisticians because gene relationships are often local. They change from one sample point to another, may only exist in a subset of the sample, and can be nonlinear or even nonmonotone. Most previous dependence measures do not specifically target local dependence relationships, and the ones that do are computationally costly. In this paper, we explore a state-of-the-art network estimation technique that characterizes gene relationships at the single cell level, under the name of cell-specific gene networks. We first show that averaging the cell-specific gene relationship over a population gives a novel univariate dependence measure, the averaged Local Density Gap (aLDG), that accumulates local dependence and can detect any nonlinear, nonmonotone relationship. Together with a consistent nonparametric estimator, we establish its robustness on both the population and empirical levels. Then, we show that averaging the cell-specific gene relationship over mini-batches determined by some external structure information (eg, spatial or temporal factor) better highlights meaningful local structure change points. We explore the application of aLDG and its minibatch variant in many scenarios, including pairwise gene relationship estimation, bifurcating point detection in cell trajectory, and spatial transcriptomics structure visualization. Both simulations and real data analysis show that aLDG outperforms existing ones.


Assuntos
Algoritmos , Análise da Expressão Gênica de Célula Única , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Análise de Sequência de RNA/métodos
5.
BMC Neurol ; 24(1): 159, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734615

RESUMO

BACKGROUND: Carbon monoxide (CO) poisoning is now one of the leading causes of poisoning-related mortality worldwide. The central nervous system is the most vulnerable structure in acute CO poisoning. MRI is of great significance in the diagnosis and prognosis of CO toxic encephalopathy. The imaging features of CO poisoning are diverse. We report atypical hippocampal lesions observed on MRI in four patients after acute CO exposure. CASE PRESENTATIONS: We report four patients who presented to the emergency department with loss of consciousness. The diagnosis of CO poisoning was confirmed on the basis of their detailed history, physical examination and laboratory tests. Brain MRI in all of these patients revealed abnormal signal intensity in hippocampi bilaterally. They all received hyperbaric oxygen therapy. The prognosis of all four patients was poor. CONCLUSION: Hippocampi, as a relatively rare lesion on MRI of CO poisoning, is of important significance both in the early and delayed stages of acute CO poisoning. In this article, we summarize the case reports of hippocampal lesions on MRI in patients with CO poisoning in recent years, in order to provide reference for the diagnosis and prognosis of CO poisoning.


Assuntos
Intoxicação por Monóxido de Carbono , Hipocampo , Imageamento por Ressonância Magnética , Humanos , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , Intoxicação por Monóxido de Carbono/complicações , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
6.
Anal Bioanal Chem ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772972

RESUMO

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) represent trace lipids with significant natural biological functions. While exogenous FAHFAs have been extensively studied, research on FAHFAs in milk remains limited, constraining our grasp of their nutritional roles. This study introduces a non-targeted mass spectrometry approach combined with chemical networking of spectral fragmentation patterns to uncover FAHFAs. Through meticulous sample handling and comparisons of various data acquisition and processing modes, we validate the method's superiority, identifying twice as many FAHFAs compared to alternative techniques. This validated method was then applied to different milk samples, revealing 45 chemical signals associated with known and potential FAHFAs, alongside findings of 66 ceramide/hexosylceramide (Cer/HexCer), 48 phosphatidyl ethanolamine/lyso phosphatidyl ethanolamine (PE/LPE), 21 phosphatidylcholine/lysophosphatidylcholine (PC/LPC), 16 phosphatidylinositol (PI), 7 phosphatidylserine (PS), and 11 sphingomyelin (SM) compounds. This study expands our understanding of the FAHFA family in milk and provides a fast and convenient method for identifying FAHFAs.

7.
Cereb Cortex ; 33(7): 3866-3881, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35989311

RESUMO

Protein quality control (PQC) is essential for maintaining protein homeostasis and guarding the accuracy of neurodevelopment. Previously, we found that a conserved EBAX-type CRL regulates the protein quality of SAX-3/ROBO guidance receptors in Caenorhabditis elegans. Here, we report that ZSWIM8, the mammalian homolog of EBAX-1, is essential for developmental stability of mammalian brains. Conditional deletion of Zswim8 in the embryonic nervous system causes global cellular stress, partial perinatal lethality and defective migration of neural progenitor cells. CRISPR-mediated knockout of ZSWIM8 impairs spine formation and synaptogenesis in hippocampal neurons. Mechanistic studies reveal that ZSWIM8 controls protein quality of Disabled 1 (Dab1), a key signal molecule for brain development, thus protecting the signaling strength of Dab1. As a ubiquitin ligase enriched with intrinsically disordered regions (IDRs), ZSWIM8 specifically recognizes IDRs of Dab1 through a "disorder targets misorder" mechanism and eliminates misfolded Dab1 that cannot be properly phosphorylated. Adult survivors of ZSWIM8 CKO show permanent hippocampal abnormality and display severely impaired learning and memory behaviors. Altogether, our results demonstrate that ZSWIM8-mediated PQC is critical for the stability of mammalian brain development.


Assuntos
Proteína Reelina , Ubiquitina , Animais , Feminino , Gravidez , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Ligases , Mamíferos/metabolismo , Serina Endopeptidases/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas do Tecido Nervoso/metabolismo
8.
J Craniofac Surg ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758573

RESUMO

OBJECTIVES: In this study, the authors aimed to evaluate the relationship between pericarotid fat density (PFD) and pathologic carotid plaque risk characteristics. METHODS: The authors retrospectively evaluated 58 patients (mean age: 66.66 ± 7.26 y, 44 males) who were subjected to both carotid endarterectomy and carotid artery computed tomography angiography (CTA) at the authors' institution. The computed tomography values of the adipose tissue around the most severe stenosis carotid artery were measured, and the removed plaques were sent to the Department of Pathology for American Heart Association (AHA) classification. The Wilcoxon signed-rank test was used to detect the difference in PFD values between the operative and nonoperative sides. According to carotid plaque risk characteristics, the associations between PFD and 4 different risk characteristic subgroups were analyzed. The Student t test and χ2 test were used to compare differences between different risk subgroups. Receiver operating characteristic curve analysis was used to evaluate the predictive efficacy of PFD for carotid plaque risk characteristics. RESULTS: The operative side had higher mean Hounsfield units (HU) values compared with the nonoperative side (P < 0.001). The AHA VI and the intraplaque hemorrhage (IPH) subgroups had higher mean HU values compared with the non-AHA VI and the non-IPH subgroups (P < 0.05). Male patients presented with IPH more than female patients (P = 0.047). The results of receiver operating characteristic curve analysis showed that the mean HU value (operative side; area under the curve: 0.729, Sensitivity (SE): 59.26%, Specificity (SP): 80.65%, P = 0.003) had a certain predictive value for diagnosing high-risk VI plaques. Pericarotid fat density ≥ -68.167 HU is expected to serve as a potential cutoff value to identify AHA VI and non-AHA VI subgroups. CONCLUSION: PFD was significantly associated with vulnerable plaques, high-risk AHA VI plaques, and IPH, which could be an indirect clinical marker for vulnerable plaques.

9.
Sheng Li Xue Bao ; 76(2): 301-308, 2024 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-38658378

RESUMO

Delayed-onset muscle soreness (DOMS) is a common phenomenon that occurs following a sudden increase in exercise intensity or unfamiliar exercise, significantly affecting athletic performance and efficacy in athletes and fitness individuals. DOMS is characterized by allodynia and hyperalgesia, and their mechanisms remain unclear. Recent studies have reported that neurotrophic factors, such as nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF), are involved in the development and maintenance of DOMS. This article provides a review of the research progress on the signaling pathways related to the involvement of NGF and GDNF in DOMS, hoping to provide novel insights into the mechanisms underlying allodynia and hyperalgesia in DOMS, as well as potential targeted treatment.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial , Mialgia , Fator de Crescimento Neural , Humanos , Mialgia/fisiopatologia , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/fisiologia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/fisiologia , Transdução de Sinais , Animais , Hiperalgesia/fisiopatologia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/fisiologia , Exercício Físico/fisiologia
10.
Cancer Sci ; 114(6): 2414-2428, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36919771

RESUMO

Previous studies have shown that gastrointestinal microbiome is associated with the development of esophageal cancer, but the relationship and molecular mechanism between esophageal microbiota and the early development of esophageal cancer remain unclear. Here, we found that Lactobacillus, Escherichia-Shigella, Rikenellaceae-RC9-gut-group, Morganella, and Fusobacterium were more abundant in early-stage esophageal cancer (EEC) tissues compared with normal esophageal tissues. The abundance of bacteria such as Prevotella, Fusobacterium, Porphyromonas, Actinobacillus, and Neisseria in advanced esophageal cancer (AEC) was higher than that in EEC. Then, we further verified that Fusobacterium nucleatum (Fn) was enriched in EEC tissues and that its abundance increased with the progression of esophageal cancer by FISH and RT-PCR. Next, we demonstrated that Fn promoted the proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Finally, we confirmed that Fn promoted ESCC proliferation by upregulating the expression of interleukin (IL)-32/proteinase 3 (PRTN3) and then activating the PI3K/AKT signaling pathway. In conclusion, Fn promoted the early development of ESCC by upregulating the expression of IL-32/PRTN3 and thereby activating the PI3K/AKT signaling pathway. A better understanding of the molecular mechanism of Fn in early esophageal cancer may contribute to the development of early screening markers to diagnose ESCC and provide new targets for treatment.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Fusobacterium nucleatum/genética , Mieloblastina/metabolismo , Regulação para Cima , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Interleucinas/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral
11.
Cancer Sci ; 114(3): 793-805, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36369883

RESUMO

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Fatores de Transcrição NFI/genética , Espécies Reativas de Oxigênio/metabolismo , Sorafenibe/farmacologia
12.
Anal Chem ; 95(48): 17937-17944, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37991222

RESUMO

Oxygen vacancy is one intrinsic defect in metal oxide materials. Interestingly, we herein found that the surface oxygen vacancy can significantly enhance the catalytic activity of Co3O4 nanowires in the luminol-H2O2 chemiluminescence (CL) reaction. 0.1 ng/mL Co3O4 nanowires containing 51.3% surface oxygen vacancies possessed ca. 2.5-fold catalytic activity of free Co2+ (the best metal ionic catalyst for the luminol-H2O2 CL reaction). The superior catalytic efficiency is attributed to the enhanced adsorption of H2O2 by surface oxygen vacancies, which in turn accelerates the cleavage of O-O bonds and generates •OH radicals. More importantly, the surface oxygen vacancy-rich Co3O4 nanowires retained about 90% catalytic activity after modification with antibodies. The surface oxygen vacancy-rich Co3O4 nanowires were used to label the secondary antibody, and one sandwich-type CL immunoassay of carcinoembryonic antigen was established. The detection limit was 0.3 ng/mL with a linear range of 1-10 ng/mL. This proof-of-concept work proves that surface oxygen vacancy-rich Co3O4 nanowires are suitable for labeling biomolecules in CL bioanalysis and biosensing.


Assuntos
Luminol , Nanofios , Luminol/química , Peróxido de Hidrogênio/análise , Oxigênio , Luminescência , Imunoensaio , Anticorpos
13.
Crit Rev Food Sci Nutr ; : 1-13, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140184

RESUMO

As an emerging group of bioactive fatty acids, monomethyl branched-chain fatty acids (mmBCFAs) have sparked the interest of many researchers both domestically and internationally. In addition to documenting the importance of mmBCFAs for growth and development, there is increasing evidence that mmBCFAs are highly correlated with obesity and insulin resistance. According to previous pharmacological investigations, mmBCFAs also exhibit anti-inflammatory effects and anticancer properties. This review summarized the distribution of mmBCFAs, which are widely found in dairy products, ruminants, fish, and fermented foods. Besides, we discuss the biosynthesis pathway in different species and detection methods of mmBCFAs. With the hope to unveil their mechanisms of action, we recapitulated detailed the nutrition and health benefits of mmBCFAs. Furthermore, this study provides a thorough, critical overview of the current state of the art, upcoming difficulties, and trends in mmBCFAs.

14.
Appetite ; 188: 106765, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37385472

RESUMO

This research investigates the impact of the introduction of plant-based meats (PBMs) on consumers' food practices. Based on the results of 21 in-depth interviews with consumers who use PBMs, this research uses practice theory to explore how the adoption of PBMs affects linked food practices and the meanings associated with these practices. We find that consumers adopt PBMs due to either a desire for meaning coherence or for practicality. Subsequently there are social and embodied ripple consequences associated with this adoption, with consumers revising their social food practices, reconfiguring their understandings of health, and re-orienting their relationship to their body. Our findings extend the research on practice theory by examining how the adoption of a new category of ideological objects shapes other linked consumption practices. Practically, our findings provide important insights for dietary, marketing and health practitioners to understand the overall impact of PBM adoption on consumers' dietary patterns and practices, and their perception about health and body.

15.
Ecotoxicol Environ Saf ; 263: 115360, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37597287

RESUMO

Rice (Oryza sativa L.) consumption represents a major route of human exposure to cadmium (Cd) and arsenic (As), especially in Asia. This study investigated the effects of adding MnSO4 (0, 200, 400, and 800 mg kg-1-1) on the formation of soil Fe/Mn oxides and Cd and As uptake in rice. The application of MnSO4 reduced soil pH, increased Eh, increased the contents of Fe/Mn oxides in the soil, and decreased the total Fe and Mn2+ contents in the porewater. It also led to lower contents of available Cd and As, higher levels of Cd and As bound to Fe/Mn oxides, and higher abundances of Thiobacillus and Syntrophobacter. Furthermore, Mn application increased the Fe and Mn contents in the root Fe/Mn plaque and decreased the grain Cd and As contents. Therefore, Mn application may modify the microbial community and porewater composition in soil, resulting in higher levels of Fe/Mn oxides in soil and Fe/Mn plaque at the root surface and in a lower accumulation of Cd and As in rice grains. Thus, Mn application can be a promising strategy for Cd and As stabilization in soils.


Assuntos
Arsênio , Oryza , Humanos , Cádmio , Manganês , Sulfatos , Óxidos , Solo , Ferro
16.
Ecotoxicol Environ Saf ; 263: 115289, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37499391

RESUMO

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.


Assuntos
Glicemia , Jejum , Metais , Selênio , Idoso , Feminino , Humanos , Teorema de Bayes , Glicemia/análise , Cobalto/urina , População do Leste Asiático , Jejum/sangue , Jejum/urina , Vida Independente , Selênio/urina , Vanádio/urina , Espectrometria de Massas , Cálcio/urina , Magnésio/urina , Molibdênio/urina , Metais/urina , Misturas Complexas/urina
17.
J Integr Neurosci ; 22(5): 122, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37735116

RESUMO

BACKGROUND: Studies have reported that the RNA-binding protein Eukaryotic Elongation Factor 1A1 (EEF1A1) is low expressed in the hippocampal region of Alzheimer's disease (AD). In addition, it is related to PARK2 activity in cells, predicting its importance in neurodegenerative diseases. However, the function of EEF1A1 in Parkinson's disease (PD) is unclear. Our study's primary objective was to knock down EEF1A1 in U251 cells and preliminarily explore the role of EEF1A1 in PD neuroinflammation. METHODS: To inhibit EEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells. Then, RNA-seq sequencing was used to determine the Differentially Expressed Genes (DEGs) resulting from the EEF1A1 knockdown. Additionally, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to find the biological processes and signaling pathways engaged in the DEGs, as well as to screen for genes associated with neuroinflammatory processes that influence the development of PD. Further Real Time - quantitative Polymerase Chain Reaction (RT-qPCR) validation experiments were performed to confirm the reliability of the sequencing results. Finally, combined with the support of related literature, the molecular mechanism of EEF1A1 in regulating the neuroinflammatory process of PD was initially explored. RESULTS: Analysis using the RNA-seq technique showed that EEF1A1 knockdown could significantly upregulate the expression of IL-6, GDF15, STC1, MT1E, GPNMB, CCL5, MT1X, A2M, and VIP genes at the transcriptional level. These nine highly elevated genes were enriched to signaling pathways linked to inflammatory processes, according to an analysis of GO and KEGG enrichment. CONCLUSIONS: EEF1A1 is involved in the regulating of IL-6, GDF15, STC1, MT1E, GPNMB, CCL5, MT1X, A2M, and VIP genes associated with the neuroinflammatory process of PD. Among them, we found that GDF15, STC1, MT1E, MT1X, GPNMB, VIP, and A2M genes were involved in delaying the neuroinflammatory process of PD, while IL-6 and CCL5 were involved in exacerbating the neuroinflammatory process, implicating that EEF1A1 may participate in the regulation of the PD neuroinflammation.


Assuntos
Eucariotos , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Interleucina-6 , Doenças Neuroinflamatórias , Reprodutibilidade dos Testes , Fatores de Transcrição , Fator 1 de Elongação de Peptídeos/genética , Glicoproteínas de Membrana
18.
Sheng Li Xue Bao ; 75(4): 595-603, 2023 Aug 25.
Artigo em Zh | MEDLINE | ID: mdl-37583047

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms, including bradykinesia, resting tremor, and progressive rigidity. More recently, non-motor symptoms of PD, such as pain, depression and anxiety, and autonomic dysfunction, have attracted increasing attention from scientists and clinicians. As one of non-motor symptoms, pain has high prevalence and early onset feature. Because the mechanism of PD-related pathological pain is unclear, the clinical therapy for treating PD-related pathological pain is very limited, with a focus on relieving the symptoms. This paper reviewed the clinical features, pathogenesis, and therapeutic strategies of PD-related pathological pain and discussed the mechanism of the chronicity of PD-related pathological pain, hoping to provide useful data for the study of drugs and clinical intervention for PD-related pathological pain.


Assuntos
Doenças do Sistema Nervoso Autônomo , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Doenças do Sistema Nervoso Autônomo/complicações , Ansiedade , Dor/etiologia
19.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4215-4230, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37802790

RESUMO

Network Meta-analysis was employed to compare the efficacy of Chinese medicine injections for activating blood and resolving stasis combined with conventional western medicine in the treatment of acute ischemic stroke and the effects on platelet aggregation rate, fibrinogen(FIB), and hypersensitive C-reactive protein(hs-CRP), with a view to providing evidence-based medicine reference for clinical medication. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase were searched for randomized controlled trial(RCT) on the treatment of acute ischemic stroke with Salvia Miltiorrhiza Ligustrazine Injection, Danhong Injection, Shuxuetong Injection, Xueshuantong Injection, Shuxuening Injection, Safflower Yellow Pigment Injection, and Ginkgo Diterpene Lactone Meglumine Injection combined with conventional western medicine. The retrieval time was from database inception to March 18, 2023. The articles were extracted by two researchers and their quality was evaluated. R 4.2.2 was used for network Meta-analysis. A total of 87 RCTs involving 8 580 patients were included. Network Meta-analysis showed that, in terms of reducing National Institutes of Health stroke scale(NIHSS) scores, the surface under the cumulative ranking curve(SUCRA) showed the order of Xueshuantong Injection + conventional western medicine(88.7%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(73.7%) > Shuxuetong Injection + conventional western medicine(69.7%) > Shuxuening Injection + conventional western medicine(51.8%) > Danhong Injection + conventional western medicine(43.7%) > Safflower Yellow Pigment Injection + conventional western medicine(36.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(35.3%) > conventional western medicine(1.7%). In terms of improving clinical total effective rate, SUCRA showed the order of Danhong Injection + conventional western medicine(63.0%) > Shuxuening Injection + conventional western medicine(59.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(58.9%) > Safflower Yellow Pigment Injection + conventional western medicine(57.1%) > Xueshuantong Injection + conventional western medicine(56.8%) > Shuxuetong Injection + conventional western medicine(54.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(50.5%) > conventional western medicine(0.03%). In terms of improving Barthel index, SUCRA showed the order of Danhong Injection + conventional western medicine(84.7%) > Shuxuetong Injection + conventional western medicine(72.4%) > Safflower Yellow Pigment Injection + conventional western medicine(61.6%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(44.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(43.2%) > Shuxuening Injection + conventional western medicine(42.2%) > conventional western medicine(1.4%). In terms of reducing platelet aggregation rate, SUCRA showed the order of Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(82.4%) > Shuxuetong Injection + conventional western medicine(81.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(40.7%) > Danhong Injection + conventional western medicine(37.3%) > conventional western medicine(8.0%). In terms of reducing FIB, SUCRA showed the order of Danhong Injection + conventional western medicine(81.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(71.9%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(70.0%) > Shuxuetong Injection + conventional western medicine(46.7%) > Xueshuantong Injection + conventional western medicine(22.6%) > conventional western medicine(8.7%). In terms of reducing hs-CRP, SUCRA showed the order of Shuxuening Injection + conventional western medicine(89.9%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(78.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(52.4%) > Danhong Injection + conventional western medicine(47.6%) > Xueshuantong Injection + conventional western medicine(43.5%) > Shuxuetong Injection + conventional Western medicine(35.6%) > conventional western medicine(2.3%). The results indicated that Xueshuantong Injection + conventional western medicine, Danhong Injection + conventional western medicine, and Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine ranked the top three. Xueshuantong Injection + conventional western medicine had the best effect on reducing NIHSS scores. Danhong Injection + conventional western medicine showed the best performance of improving clinical total effective rate, improving Barthel index, and reducing FIB in the blood. Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine had the best effect on reducing platelet aggregation rate in the blood. Shuxuening Injection + conventional western medicine had the best effect on reducing hs-CRP. However, more high-quality RCTs are needed for verification in the future to provide more reliable evidence-based medical reference.


Assuntos
Diterpenos , Medicamentos de Ervas Chinesas , AVC Isquêmico , Humanos , Medicina Tradicional Chinesa , AVC Isquêmico/tratamento farmacológico , Metanálise em Rede , Proteína C-Reativa , Medicamentos de Ervas Chinesas/uso terapêutico , Adjuvantes Farmacêuticos , Lactonas , Meglumina
20.
Anal Chem ; 94(24): 8642-8650, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35679593

RESUMO

Defect engineering is an effective strategy to improve the catalytic activity of metal oxides, and quantitative characterization of surface defects is thus vital to the understanding and application of metal oxide catalysts. Herein, we found that ZnO nanoparticles with oxygen vacancy could trigger the luminol-H2O2 system to emit a strong chemiluminescence (CL), and the CL intensity was strongly dependent on the oxygen vacancy of the ZnO nanoparticles. The mechanism of this CL reaction was discussed by means of the electron-spin resonance spectrum, X-ray photoelectron spectrum (XPS), and CL spectrum. The oxygen vacancy-dependent CL was attributed to the ability of the oxygen vacancy to readily adsorb and further dissociate H2O2 into active •OH radicals. Taking advantage of this oxygen vacancy-dependent CL, we presented one method for quantifying the oxygen defects in ZnO. Compared with the current evaluation techniques (XPS and Raman spectroscopy), this CL method is rapid, low-cost, and easy to operate. This work introduces the CL technique into the field of material structure-property evaluation, and provides a new approach for exploring the defect function in ZnO defect engineering.


Assuntos
Luminescência , Óxido de Zinco , Peróxido de Hidrogênio/química , Luminol/química , Óxidos , Oxigênio
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