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1.
J Org Chem ; 89(14): 9750-9754, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38940722

RESUMO

Herein, a photocatalytic umpolung strategy for reductive carboxylation of imines for the synthesis of α-amino acids was disclosed. Carbon dioxide radical anion (CO2•-) generated from formate is the key single electron reductant in the reactions. An unprecedentedly broad substrate scope of imines with excellent reaction yields was obtained with carbon dioxide (CO2) and formate salt as carbon sources.

2.
Chin Med Sci J ; 39(3): 198-210, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39229794

RESUMO

With the progress of aging, the incidence of vascular calcification (VC) gradually increases, which is correlated with cardiovascular events and all-cause death, aggravating global clinical burden. Over the past several decades, accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC. Unfortunately, none of the current interventions have achieved clinical effectiveness on reversing or curing VC. The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.


Assuntos
Calcificação Vascular , Humanos , Calcificação Vascular/terapia , Tomada de Decisão Clínica , Envelhecimento
3.
J Biol Chem ; 298(5): 101818, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35278432

RESUMO

Gonadal white adipose tissue (gWAT) can regulate gametogenesis via modulation of neuroendocrine signaling. However, the effect of gWAT on the local microenvironment of the gonad was largely unknown. Herein, we ruled out that gWAT had a neuroendocrine effect on gonad function through a unilateral lipectomy strategy, in which cutting off epididymal white adipose tissue could reduce seminiferous tubule thickness and decrease sperm counts only in the adjacent testis and epididymis of the affected gonad. Consistent with the results in males, in females, ovary mass was similarly decreased by lipectomy. We determined that the defects in spermatogenesis were mainly caused by augmented apoptosis and decreased proliferation of germ cells. Transcriptome analysis suggested that lipectomy could disrupt immune privilege and activate immune responses in both the testis and ovary on the side of the lipectomy. In addition, lipidomics analysis in the testis showed that the levels of lipid metabolites such as free carnitine were elevated, whereas the levels of glycerophospholipids such as phosphatidylcholines and phosphatidylethanolamines were decreased, which indicated that the metabolic niche was also altered. Finally, we show that supplementation of phosphatidylcholine and phosphatidylethanolamine could partially rescue the observed phenotype. Collectively, our findings suggest that gWAT is important for gonad function by not only affecting whole-body homeostasis but also via maintaining local metabolic and immune niches.


Assuntos
Tecido Adiposo Branco , Gônadas , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Epididimo , Feminino , Masculino , Camundongos , Espermatogênese , Testículo/metabolismo
4.
J Cell Mol Med ; 26(23): 5779-5793, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36401602

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive impairment and abnormal mental behaviour. There is currently no effective cure. The development of early diagnostic markers and the mining of potential therapeutic targets are one of the important strategies. This study aimed to explore potential biomarkers or therapeutic targets related to AD in the hippocampus and prefrontal cortex, two brain regions highly related to AD. Differentially expressed genes and miRNAs between AD patients and healthy controls were obtained from the Gene Expression Omnibus database. The mRNA-miRNA network was constructed and key genes involved in AD were screened out by protein-protein interaction analysis, and were subsequently verified by independent datasets and qPCR in an AD mouse model. Our findings showed that six hub genes including CALN1, TRPM7, ATR, SOCS3, MOB3A and OGDH were believed to be involved in the pathogenesis of AD. Western blot analysis further determined that CALN1, ATR and OGDH were the possible biomarkers and therapeutic targets for AD. In addition, 6 possible miRNAs biomarkers have also been verified by qPCR on AD animal models. Our findings may benefit clinical diagnosis and early prevention of AD.


Assuntos
Doença de Alzheimer , Hipocampo , MicroRNAs , Córtex Pré-Frontal , Animais , Camundongos , Doença de Alzheimer/genética , Modelos Animais de Doenças , MicroRNAs/genética , RNA Mensageiro/genética
5.
Physiol Mol Biol Plants ; 28(2): 439-454, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35400891

RESUMO

Vicatia thibetica de Boiss.: a herb in the family Apiaceae, has been used for over a hundred years as an essential medicinal and edible plant in the Bai ethnic group of Dali City. However, due to the lack of study on plastid genomes of V. thibetica, studies of comparison and phylogeny with other related species remain scarce. In the current study, we assembled, annotated, and characterized the entire chloroplast (cp) genome of V. thibetica through high-throughput sequencing for the first time, compared with published whole chloroplast genomes from the same family. A phylogenetic analysis of the chloroplast genome has also been performed. The whole chloroplast genome of V. thibetica was 145,796 in size and consisted of a large single-copy region (LSC; 92,186 bp), a small single-copy region (SSC; 17,452 bp), and a pair of inverted repeat regions (IRs; 18,079 bp) forming a circular quadripartite structure. Annotation resulted in 128 genes, including 84 protein-coding genes (PCGs), 35 transfer RNA genes (tRNAs), eight ribosomal genes (rRNAs), and one pseudogene. Repeat sequence analysis displayed V. thibetica plastid genome contains 75 simple repeats, 37 long repeats, and 29 tandem repeats. Compared with the cp genome of other Apiaceae species, a common feature was that the IR regions of the genome were more conservative compared to the LSC and SSC regions. Highly variable hotspots included rps16, ndhC-trnV-UAC, clpP, ycf1, and ndhB in the genomes, which supply valuable molecular markers for phylogeny, identification, and classification in the Apiaceae family. The results of phylogenetic analysis strongly supported the genus Vicatia as an independent genus in the family Apiaceae, in which the closest affinities to the related species of Angelica, Peucedanum, and Ligusticum were observed. In conclusion, the first chloroplast genome of Vicatia reported in this study may  improve our understanding of phylogenetic relationship of different genera of Apiaceae. In addition, the current data will be valuable as chloroplast genomic resource for species identification and population genetics. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01154-y.

6.
FASEB J ; 34(5): 7144-7159, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32275117

RESUMO

Disrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells. Co-IP assays confirmed that TRAF3 forms a complex with TRAF2 and cIAP1 and mediates ubiquitin and degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown of ULK1 in THP-1 cells significantly promoted LPS/Ng-induced inflammasome by activating caspase 1 and mature IL-1ß. Apoptosis inducing factor (AIF) translocation from mitochondrial to nuclear was observed in ULK1-deficient THP-1 cells under LPS/Ng stimulation, which mediates LPS/Ng-induced cell death in ULK1 deficient macrophages. In conclusion, this study identified a novel role of TRAF3 in regulation of ULK1 ubiquitination and inflammasome signaling and provided molecular mechanisms by which ubiquitination of ULK1 controls mitochondrial ROS production, inflammasome activity, and AIF-dependent pyroptosis.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/deficiência , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Inflamassomos/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Monócitos/citologia , Monócitos/metabolismo , Nigericina/farmacologia , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células THP-1 , Fator 3 Associado a Receptor de TNF/deficiência , Fator 3 Associado a Receptor de TNF/genética , Ubiquitinação/efeitos dos fármacos
7.
FASEB J ; 34(5): 6570-6581, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32246801

RESUMO

Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Fatores de Transcrição ARNTL/fisiologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/imunologia , Inflamação/patologia , Microglia/patologia , Doença de Parkinson/patologia , Animais , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurotoxinas/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo
8.
Med Sci Monit ; 25: 5191-5200, 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31300636

RESUMO

BACKGROUND Aspirin hyporesponsiveness increases the risk of ischemic events. Therefore, it is important to investigate the factors influencing aspirin hyporesponsiveness. MATERIAL AND METHODS Patients aged 60 years or older who did not take aspirin before enrollment were included, with aspirin 100 mg/day administered after enrollment. The arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay to evaluate aspirin responsiveness. Patients with Ara in the upper quartile after taking aspirin were assigned to the aspirin hyporesponsive group (Ara-Q4). RESULTS A total of 292 elderly patients were included. The median value of Ara after taking aspirin was 5.87% (interquartile range 3.86-10.04%). Compared with the aspirin non-hyporesponsive group (Ara-Q1-3, Ara ≤10.04%, n=220), the level of uric acid (UA) (341.30 µmol/L vs. 299.10 µmol/L, p=0.027) and the ratios of ß-blockers (9.72% vs. 2.27%, p=0.015) and diuretics (6.94% vs. 1.36%, p=0.036) were higher in the aspirin hyporesponsive group (Ara-Q4, Ara >10.04%, n=72). After multivariate adjustment, the results demonstrated baseline Ara (odds ratio [OR]: 1.030, 95% confidence interval [CI]: 1.004-1.056, p=0.021), UA level (OR: 1.003, 95% CI: 1.000-1.006, p=0.038), and ß-blockers use (OR: 5.487, 95% CI: 1.515-19.870, p=0.010) were independently and positively associated with aspirin hyporesponsiveness. CONCLUSIONS This study found that baseline Ara, UA level, and ß-blockers use were independently and positively associated with aspirin hyporesponsiveness in elderly Chinese patients, which needs to be validated in large-scale studies.


Assuntos
Aspirina/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Biomarcadores Farmacológicos/metabolismo , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária , Ácido Úrico/análise
9.
Environ Geochem Health ; 40(4): 1585-1599, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29392546

RESUMO

Groundwater contamination with high arsenic (As) levels has caused serious health problem in Jianghan Plain. This study presents a framework to evaluate the results and their probable influencing factors of non-carcinogenic risk and carcinogenic risk in Shahu Village. An appropriate health risk assessment for residents exposing to As through ingestion and dermal contact pathways is also discussed in the paper. Hazard quotient (HQ) and target cancer risk (TR) are adopted to compute the non-carcinogenic and carcinogenic effects for residents, respectively. Monte Carlo simulation technique is used to quantify the uncertainty of the risk assessment. The assessment results show that the HQs and TRs of 10-m-deep and 25-m-deep wells exhibit seasonal variations with higher values in rainy season and lower values in dry season. The HQ values exceeding 1 at the depths of 10 (from 0.09 to 23.21 m) and 25 m (from 0.29 to 130.55 m) account for 61 and 94%, respectively, which associate with the As contents distribution in the aquifer sediments. The estimated TR values at the depths of 10 (from 3.86E-05 to 1.04E-02) and 25 m (from 1.32E-04 to 5.87E-02) exceeding the highest acceptable standard (10-4) account for 95 and 100%, respectively. Comparison of the two exposure pathways, the ingestion exposure contributes much more than the dermal contact exposure for both non-carcinogenic risk and carcinogenic risk. The results of sensitivity analysis indicate that a more accurate measurement and better definition of probability distributions for As concentration in the groundwater can increase the accuracy of health risk assessment in Jianghan Plain. The findings demonstrate the importance of the drinking water safety, and the government should take measures to ensure the drinking water safety.


Assuntos
Arsênio/análise , Arsênio/toxicidade , Exposição Dietética , Água Potável/análise , Exposição Ambiental , Água Subterrânea/química , Pele/efeitos dos fármacos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , China , Medição de Risco
10.
Environ Monit Assess ; 190(10): 599, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30238229

RESUMO

East Lake is a shallow lake (in Wuhan, China) where cyanobacteria blooms occurred frequently from 1970 to 1985. During the study period, all Carlson trophic state index values were > 50, indicating that East Lake is in a eutrophic state. In this study, phycocyanin concentrations were measured through phycocyanin fluorometry for rapid assessment of cyanobacterial abundance. The smoothing splines of the optimal generalized additive model (GAM) indicated that Secchi depth (SD), total phosphorus (TP) and dissolved oxygen (DO) concentrations, electrical conductivity (EC), chemical oxygen demand (COD), and ratios of total nitrogen (TN) to TP (TN:TP) were the main environmental factors in a moderate nonlinear relationship with cyanobacterial phycocyanin concentrations in East Lake. The shape of the GAM smoother can be used to quantify the relationship between a response variable and an explanatory variable in the scatterplot. Phycocyanin concentrations were sharply and negatively related to both SD and EC when the SD was 20-80 cm and EC was > 270 mg/L. Phycocyanin concentrations increased with concentrations of TP, DO, and COD. Phycocyanin concentrations increased sharply with TP concentrations when TP concentrations were > 0.10 mg/L and approached to a constant when DO concentrations were > 8.20 mg/L. Approximately, 85% of the phycocyanin concentrations were negatively correlated with TN:TP of < 26. In summary, organic compounds and TP were inferred to the key factors limiting the potential growth of cyanobacteria in East Lake. These change points/thresholds of smoothing splines of aforementioned variables may serve as a framework for managing the cyanobacterial growth.


Assuntos
Cianobactérias/crescimento & desenvolvimento , Modelos Estatísticos , Ficocianina/análise , China , Cianobactérias/isolamento & purificação , Monitoramento Ambiental , Eutrofização , Fluorescência , Fluorometria , Lagos/química , Nitrogênio/análise , Fósforo/análise
11.
Anal Chem ; 89(12): 6678-6685, 2017 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-28520400

RESUMO

There is a great demand to measure protein-ligand interactions in rapid and low cost way. Here, we developed a microfluidic droplet-based thermal shift assay (dTSA) system for high-throughput screening of small-molecule protein ligands. The system is composed of a nanoliter droplet array chip, a microfluidic droplet robot, and a real-time fluorescence detection system. Total 324 assays could be performed in parallel in a single chip with an 18 × 18 droplet array. The consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole scale), which is significantly reduced by over 3 orders of magnitude compared with those in 96- or 384-well plate-based systems. We also observed the implementation of TSA in nanoliter droplet format could substantially improve assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which can be ascribed to the enhanced thermal conduction in small volume reactors. The dTSA system was optimized by studying the effect of droplet volumes, as well as protein and fluorescent dye (SYPRO Orange) concentrations. To demonstrate its potential in drug discovery, we applied the dTSA system in screening inhibitors of human thrombin with a commercial library containing 100 different small molecule compounds, and two inhibitors were successfully identified and confirmed.


Assuntos
Ensaios de Triagem em Larga Escala , Técnicas Analíticas Microfluídicas , Inibidores de Serina Proteinase/química , Bibliotecas de Moléculas Pequenas/química , Trombina/química , Fluorescência , Corantes Fluorescentes/química , Humanos , Ligantes , Tamanho da Partícula , Inibidores de Serina Proteinase/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Temperatura , Trombina/antagonistas & inibidores
12.
Anal Chem ; 89(1): 822-829, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27959506

RESUMO

Here we developed the surface-assisted multifactor fluid segmentation (SAMFS), an automated, fast, and flexible approach for generating a two-dimensional droplet array with tunable droplet volumes, for multivolume digital polymerase chain reaction (PCR). The SAMFS was developed based on the combination of robotic liquid handling and surface-assisted droplet generation techniques, where a continuous aqueous stream that flowed out from a capillary probe was segmented and immobilized on hydrophilic micropillars of a microchip into massive oil-covered droplets with the probe rapidly scanning over the microchip. We studied various factors affecting the droplet generation process, including micropillar top area, distance between adjacent micropillars, aqueous stream flow rate, and microchip moving speed, and demonstrated a high droplet generation throughput up to 50 droplets/s and a largest droplet volume adjusting range from 0.25 to 350 nL. The SAMFS approach was adopted to form an oil-covered array of 994 droplets with four different volumes (1.2, 6, 30, and 150 nL droplets) required for multivolume digital PCR within 8 min. The droplet array system was applied in absolute quantification of plasmid DNA under the multivolume digital PCR mode with a dynamic range spanning 4 orders of magnitude, as well as measurement of HER2 expression levels in different breast cancer cell lines. The results are consistent to those obtained by quantitative real-time PCR method, while the present one has higher precision.


Assuntos
Neoplasias da Mama/genética , DNA/genética , Técnicas Analíticas Microfluídicas , Reação em Cadeia da Polimerase em Tempo Real , Receptor ErbB-2/genética , Linhagem Celular Tumoral , DNA/análise , Feminino , Perfilação da Expressão Gênica , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Tamanho da Partícula , Plasmídeos , Reação em Cadeia da Polimerase em Tempo Real/instrumentação , Receptor ErbB-2/análise , Propriedades de Superfície
13.
Neurochem Res ; 40(6): 1211-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25896296

RESUMO

Notch signalling pathway plays an essential role in the development of cochlea, which inhibits the proliferation of hair cells. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea, which presents strong antioxidant activation and has been applied for anti-cancer and anti-inflammatory. In this study, we treated the cochlear explant cultures with EGCG and found that EGCG can protect cochlear hair cells from ototoxic drug gentamicin. We demonstrated that EGCG could down-regulate the expression of Notch signalling pathway target genes, such as Hes1, Hes5, Hey1 and Hey5. However, the Notch pathway ligands such as Delta1, Jag1 and Jag2 were not affected by EGCG. To further illustrate the mechanism of recover cochlear hair cells, we demonstrated that EGCG inhibited the activity of γ-secrectase to suppress Notch signalling pathway and promoted the proliferation and regeneration of hair cells in the damaged cochlea. Our results suggest for the first time the role of EGCG as an inhibitor of the Notch signalling pathway, and support its potential value in hearing-impaired recovery in clinical therapy.


Assuntos
Células Ciliadas Auditivas/efeitos dos fármacos , Polifenóis/farmacologia , Receptores Notch/antagonistas & inibidores , Chá/química , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Proliferação de Células/efeitos dos fármacos , Cóclea/lesões , Regulação para Baixo/efeitos dos fármacos , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Gentamicinas/toxicidade , Humanos , Técnicas In Vitro , Mecanotransdução Celular , Camundongos , Camundongos Transgênicos , Inibidores da Síntese de Proteínas/toxicidade , Regeneração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
J Neurosci ; 33(45): 17884-96, 2013 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-24198377

RESUMO

Nav1.8 is a tetrodotoxin-resistant voltage-gated sodium channel selectively expressed in primary sensory neurons. Peripheral inflammation and nerve injury induce Nav1.8 accumulation in peripheral nerves. However, the mechanisms and related significance of channel accumulation in nerves remains unclear. Here we report that KIF5B promotes the forward transport of Nav1.8 to the plasma membrane and axons in dorsal root ganglion (DRG) neurons of the rat. In peripheral inflammation induced through the intraplantar injection of complete Freund's adjuvant, increased KIF5 and Nav1.8 accumulation were observed in the sciatic nerve. The knock-down of KIF5B, a highly expressed member of the KIF5 family in DRGs, reduced the current density of Nav1.8 in both cultured DRG neurons and ND7-23 cells. Overexpression of KIF5B in ND7-23 cells increased the current density and surface expression of Nav1.8, which were abolished through brefeldin A treatment, whereas the increases were lost in KIF5B mutants defective in ATP hydrolysis or cargo binding. Overexpression of KIF5B also decreased the proteasome-associated degradation of Nav1.8. In addition, coimmunoprecipitation experiments showed interactions between the N terminus of Nav1.8 and the 511-620 aa sequence in the stalk domain of KIF5B. Furthermore, KIF5B increased Nav1.8 accumulation, Nav1.8 current, and neuronal excitability detected in the axons of cultured DRG neurons, which were completely abolished by the disruption of interactions between KIF5B and the N terminus of Nav1.8. Therefore, our results reveal that KIF5B is required for the forward transport and axonal function of Nav1.8, suggesting a mechanism for axonal accumulation of Nav1.8 in inflammatory pain.


Assuntos
Axônios/metabolismo , Gânglios Espinais/metabolismo , Cinesinas/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Neurônios/metabolismo , Potenciais de Ação/fisiologia , Animais , Membrana Celular/metabolismo , Células Cultivadas , Gânglios Espinais/citologia , Inflamação/metabolismo , Cinesinas/genética , Masculino , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Neurônios/citologia , Transporte Proteico/fisiologia , Ratos , Ratos Sprague-Dawley
15.
Huan Jing Ke Xue ; 45(8): 4470-4483, 2024 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-39168667

RESUMO

Volatile organic compounds (VOCs) from the wooden furniture-manufacturing industry are an important emission source. To study the emission characteristics of VOCs from the wooden furniture-manufacturing industry and associated environmental impacts, nine typical wooden furniture manufacturers in China were selected to carry out sample collection and VOCs detection. The maximum incremental reactivity (MIR) method and secondary organic aerosol (SOA) formation potential method were used to quantify the corresponding contributions to the generation of O3 and SOA. The results showed that: ① The concentrations of VOCs emitted from different types of coating exhaust gas were different. The emission concentration of VOCs in solvent-based coating exhaust gas was significantly higher than that in water-based coating exhaust gas and ultra-violet (UV) coating exhaust gas, and the VOCs emission concentrations ranged between 2.82 - 155.37, 1.13 - 104.45, and 0.57 - 1.15 mg·m-3, respectively. ② The main organic group in solvent-based coating exhaust gas was esters, accounting for 45.88%, and butyl acetate (31.07%) was the main VOCs species. The main organic group in water-based coating exhaust gas and UV coating exhaust gas was alcohols, and the main VOCs species in water-based coating exhaust gas and UV coating exhaust gas were both ethanol, accounting for 46.63% and 34.32%, respectively. ③ The OFP of VOCs emitted by solvent-based coating, water-based coating, and UV coating were 149.23, 50.90, and 1.87 mg·m-3, respectively, and the primary contributing components of OFP of different types of coating were m/p-xylene (26.61%), ethanol (36.35%), and ethanol (23.98%), respectively. ④ The SOA of VOCs emitted by solvent-based coating, water-based coating, and UV coating were 0.76, 0.25, and 0.01 mg·m-3, respectively. The SOA generation of various types of coating was dominated by aromatics(96.35%-98.96%), and the main active compounds were toluene, ethylbenzene, and xylene. ⑤ Comparing the environmental impact of exhaust gas from solvent-based coating, water-based coating, and UV coating, it was found that the OFP and SOA generated by the VOCs emitted from solvent-based coating were much higher than those for water-based coating and UV coating. Therefore, the implementation of water-based coating and UV coating substitution strategy from the source could effectively reduce VOCs emissions and abate OFP and SOA productions.

16.
Zhen Ci Yan Jiu ; 49(10): 1084-1091, 2024 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-39433370

RESUMO

OBJECTIVES: To explore the efficacy of electroacupuncture (EA) based on the "ascending lucidity and descending turbidity" theory in patients with diabetic gastrointestinal dysfunction and its regulatory effect on gut microbiota. METHODS: A total of 48 patients with diabetic gastrointestinal dysfunction were randomly divided into the EA group (24 cases, 3 cases dropped-off) and the control group (24 cases, no dropped off). Both groups received blood glucose control and basic symptomatic treatment. EA (15 Hz/100 Hz) was applied to Zhongwan (CV12), Tianshu (ST25), Zhongfu (LU1), bilateral Zhangmen (LR13), bilateral Taibai (SP3), bilateral Taiyuan (LU9), bilateral Zusanli (ST36), and bilateral Shangjuxu (ST37) in the EA group. Sham EA was applied to corresponding non-acupoints without electric stimulation in the control group. Both groups received treatment for 30 min per time, once daily, for a total of 5 treatments followed by a 2-day break, over a consecutive period of 2 weeks. Symptoms were evaluated by gastrointestinal symptom rating scale (GSRS) and gastroparesis cardinal symptom index (GCSI) before and after treatment, and 4 weeks after treatment. During the treatment period, fasting blood glucose levels were monitored daily. Stool samples were collected before and after treatment for 16S rDNA sequencing analysis to examine changes in gut microbiota. RESULTS: Compared with the control group, GSRS and GCSI scores in the EA group were significantly decreased (P<0.001) after treatment and at follow-up at the same time point, and compared with those before treatment, GSRS and GCSI scores in the EA group were significantly decreased after treatment and at follow-up (P<0.001). After treatment, the 16S rDNA sequencing showed that at the phylum level, the ratio of Proteobacteria in the EA group was higher than that in the control group (FDR<0.05). At the genus level, a total of 18 different gut microbiota were identified between the two groups. Compared to the control group, patients in the EA group showed a significant decrease in the abundance of Pseudomonas and Alkalibacter (FDR<0.05), while the abundance of the remaining 16 gut microbiota was significantly increased (FDR<0.05). Compared to the baseline, the EA group showed a significant up-regulation of Olsenella (FDR<0.05) and a significant down-regulation of Pseudomonas (FDR<0.05) after treatment. CONCLUSIONS: EA based on the "ascending lucidity and descending turbidity" theory can effectively improve the symptoms of patients with diabetic gastrointestinal dysfunction. EA can also affect the distribution of gut microbiota by up-regulating the levels of certain beneficial bacteria and suppressing pathogenic bacteria .


Assuntos
Eletroacupuntura , Microbioma Gastrointestinal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Pontos de Acupuntura , Resultado do Tratamento , Gastroenteropatias/terapia , Gastroenteropatias/microbiologia , Complicações do Diabetes/terapia , Complicações do Diabetes/microbiologia , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação
17.
Fitoterapia ; 175: 105926, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38537887

RESUMO

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Hiperuricemia , Ácido Úrico , Xantina Oxidase , Animais , Camundongos , Hiperuricemia/tratamento farmacológico , Masculino , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ácido Úrico/sangue , Xantina Oxidase/metabolismo , Modelos Animais de Doenças , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Rim/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Transportadores de Ânions Orgânicos/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia
18.
J Hazard Mater ; 480: 136371, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39488975

RESUMO

Radionuclide contamination has become a global environmental concern due to the high mobility and toxicity of certain isotopes. Bioreduction mediated by electrochemically active bacteria (EAB) with unique extracellular electron transfer (EET) capability is recognized as a promising approach for nuclear waste treatment. However, it is difficult to achieve bidirectional regulation of EET pathway through traditional genetic manipulation, limiting the bioremediation application of EAB. Here, we designed and optimized a novel Esa quorum sensing (EQS) system for highly efficient gene expression and interleaved cellular functional output. By promoting dimethyl sulfoxide reductase at low cell density and increasing the synthesis of electron conductive complex and flavins at high cell density, the EQS system dynamically switched the extracellular respiratory pathway of Shewanella oneidensis MR-1 according to cell density. The engineered strain exhibited precise switching and substantial improvement in the extracellular remediation of multiple nuclides, sequentially increasing the reduction of iodine IO3- and uranium U(VI) by 2.51- and 2.05-fold compared with the control, respectively. Furthermore, a mobile bacterial biofilm material was fabricated for collecting uranium precipitates coupled with U(VI) reduction. This work clearly demonstrates that EQS system contributes to the bidirectional regulation of EET pathway in EAB, providing an effective and refined strategy for bioremediation of multi-nuclide contamination.

19.
Front Oncol ; 14: 1339582, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220647

RESUMO

We illustrated a rare case of malignant solitary fibrous tumor (MSFT) with epithelioid morphology in the occipital region of a 59-year-old female, in which a rare NAB2ex7-STAT6 exon15/16 double fusion subtype was detected by the Next-generation sequencing (NGS) and STAT6 immunohistochemistry (IHC) was diffusely and strongly positively expressed, without recurrence after 20 months of postoperative follow-up. The morphological and molecular genetic aspects and the differential diagnosis are described, and the relevant literature was assessed in order to broaden our understanding and diagnostic capability of this malignancy.

20.
J Chromatogr A ; 1705: 464181, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37442071

RESUMO

The hollow MCM-48 polyethyleneimine carboxyphenylboronic acid molecularly imprinted polymers (H-MPC@MIPs) were synthesized to efficiently and selectively separate and enrich the ovalbumin (OVA) in egg white samples. Polyethyleneimine contained enough active amino groups to increase the amount of boric acid molecules modified to silica nanoparticles. Meanwhile, the materials were etched to enhance the adsorption effect. The H-MPC@MIPs exhibited a rapid adsorption equilibrium rate (within 30 min) and outstanding adsorption capacity for OVA (1334.1 mg g-1). It possessed a good reusability after 5 cycles. In addition, both the high density and the imprinting action of boric acid were essential for enhancing the identification and binding of OVA. The OVA in egg white samples was successfully selectively enriched using this method.


Assuntos
Impressão Molecular , Nanopartículas , Ovalbumina , Polímeros/química , Polietilenoimina , Nanopartículas/química , Adsorção
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