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1.
Pharmacol Biochem Behav ; 234: 173677, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37967673

RESUMEN

BACKGROUND: Depression is a highly prevalent comorbidity arising in patients with Parkinson's disease (PD). However, depression in patients with PD is poorly treated. Hydrogen sulfide (H2S), a neuromodulator, has the potential to relieve depression. OBJECTIVE: To investigate whether H2S attenuates depression-like behaviours in a rat model of PD and examine the underlying mechanisms. METHODS: We utilised rotenone to develop a PD model with subcutaneous injections in the dorsal cervical region of Sprague-Dawley rats. The depression-like behaviours in the rotenone-induced PD model rats were assessed through forced swimming, tail suspension, open field, novelty-suppressed feeding, and elevated plus-maze tests. The expression of postsynaptic density protein-95 and synapsin-1, related to synaptic plasticity, was detected using Western blot in the hippocampus. The hippocampal ultrastructure, including the synaptic density, length of the synaptic active zone, postsynaptic density thickness, and synaptic gap width, was detected using transmission electron microscopy. RESULTS: We proved that sodium hydrosulfide (NaHS; a donor of H2S) significantly attenuated the depression-like behaviours and disorders of hippocampal synaptic plasticity in rotenone-induced PD rats. Furthermore, inhibition of the hippocampal Warburg effect by 2-deoxyglucose abolished NaHS-enhanced hippocampal synaptic plasticity and reversed NaHS-attenuated depression-like behaviours in the rotenone-induced PD rats. CONCLUSION: H2S attenuates PD-associated depression by improving the hippocampal synaptic plasticity in a hippocampal Warburg effect-dependent manner.


Asunto(s)
Sulfuro de Hidrógeno , Enfermedad de Parkinson , Humanos , Ratas , Animales , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/uso terapéutico , Sulfuro de Hidrógeno/metabolismo , Depresión/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Ratas Sprague-Dawley , Rotenona/farmacología , Rotenona/metabolismo , Plasticidad Neuronal , Hipocampo/metabolismo
2.
Front Microbiol ; 14: 1291540, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38143864

RESUMEN

Carbapenem-resistant ST11_KL64 Klebsiella pneumoniae emerged as a significant public health concern in Taiwan, peaking between 2013 and 2015, with the majority of isolates exhibiting OXA-48 as the sole carbapenemase. In this study, we employed whole-genome sequencing to investigate the molecular underpinnings of ST11_KL64 isolates collected from 2013 to 2021. Phylogenomic analysis revealed a notable genetic divergence between the ST11_KL64 strains in Taiwan and those in China, suggesting an independent evolutionary trajectory. Our findings indicated that the ST11_KL64_Taiwan lineage originated from the ST11_KL64 lineage in Brazil, with recombination events leading to the integration of ICEKp11 and a 27-kb fragment at the tRNAASN sites, shaping its unique genomic landscape. To further elucidate this unique sublineage, we examined the plasmid contents. In contrast to ST11_KL64_Brazil strains, which predominantly carried blaKPC-2, ST11_KL64_Taiwan strains exhibited the acquisition of an epidemic blaOXA-48-carrying IncL plasmid. Additionally, ST11_KL64_Taiwan strains consistently harbored a multi-drug resistance IncC plasmid, along with a collection of gene clusters that conferred resistance to heavy metals and the phage shock protein system via various Inc-type plasmids. Although few, there were still rare ST11_KL64_Taiwan strains that have evolved into hypervirulent CRKP through the horizontal acquisition of pLVPK variants. Comprehensive characterization of the high-risk ST11_KL64 lineage in Taiwan not only sheds light on its epidemic success but also provides essential data for ongoing surveillance efforts aimed at tracking the spread and evolution of ST11_KL64 across different geographical regions. Understanding the molecular underpinnings of CRKP evolution is crucial for developing effective strategies to combat its emergence and dissemination.

3.
Curr Microbiol ; 80(12): 393, 2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37897506

RESUMEN

A novel endophytic actinobacterial strain, designated MQZ13P-5T, was isolated from a piece of bark of Sonneratia apetala, collected from Guangxi Zhuang Autonomous Region, China. This strain was Gram-stain positive, aerobic, non-spore-forming, non-motile and rod-shaped. Comparative 16S rRNA gene sequence analysis showed that strain MQZ13P-5T was related to the genus Phycicoccus with exhibiting the highest similarity (98.0%) to Phycicoccus endophyticus IP6SC6T. The phylogenetic trees based on 16S rRNA gene sequences and core genes indicated that strain MQZ13P-5T belonged to the genus Phycicoccus and could not be assigned to any described species. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain MQZ13P-5T and type strains of Phycicoccus species were less than 84% and 27%, respectively, below the thresholds for species delineation. This strain showed chemotaxonomic and phenotypic properties consistent with its classification in the genus Phycicoccus. Based on the taxonomic data, strain MQZ13P-5T should represent a novel species of the genus Phycicoccus, for which the name Phycicoccus sonneraticus sp. nov. is proposed, with the type strain MQZ13P-5T (= CGMCC 1.18744T = JCM 34337T).


Asunto(s)
Actinomycetales , Ácidos Grasos , Ácidos Grasos/análisis , Fosfolípidos/análisis , Filogenia , ARN Ribosómico 16S/genética , Corteza de la Planta/química , Corteza de la Planta/microbiología , Análisis de Secuencia de ADN , Técnicas de Tipificación Bacteriana , China , ADN Bacteriano/genética , Composición de Base
4.
Neurosci Biobehav Rev ; 153: 105403, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37742989

RESUMEN

The role of gut dysbiosis in depression is well established. However, recent studies have shown that gut microbiota is regulated by intestinal epithelial cell (IEC) mitochondria, which has yet to receive much attention. This review summarizes the recent developments about the critical role of IEC mitochondria in actively maintaining gut microbiota, intestinal metabolism, and immune homeostasis. We propose that IEC mitochondrial dysfunction alters gut microbiota composition, participates in cell fate, mediates oxidative stress, activates the peripheral immune system, causes peripheral inflammation, and transmits peripheral signals through the vagus and enteric nervous systems. These pathological alterations lead to brain inflammation, disruption of the blood-brain barrier, activation of the hypothalamic-pituitary-adrenal axis, activation of microglia and astrocytes, induction of neuronal loss, and ultimately depression. Furthermore, we highlight the prospect of treating depression through the mitochondria of IECs. These new findings suggest that the mitochondria of IECs may be a newly found important factor in the pathogenesis of depression and represent a potential new strategy for treating depression.

5.
Int J Biol Macromol ; 248: 125951, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37499724

RESUMEN

Coriolus versicolor, a popular traditional Chinese medicinal herb, is widely used in China to treat spleen and liver diseases; however, the beneficial effects of C. versicolor polysaccharides (CVPs) on nonalcoholic fatty liver disease (NAFLD) remain elusive. Herein we isolated and purified a novel CVP (molecular weight, 17,478 Da) from fermented mycelium powder. This CVP was composed of mannose, galacturonic acid, glucose, galactose, xylose, and fucose at a molar ratio of 22:1:8:15:10:3. Methylation, gas chromatography-mass spectrometry, and nuclear magnetic resonance analyses indicated that the CVP backbone consisted of →1)-ß-D-Man-(6,4→1)-α-D-Gal-(3→1)-α-D-Man-(4→1)-α-D-Gal-(6→, with branches of →1)-α-D-Glc-(6→1)-α-D-Man-(4,3→1)-ß-D-Xyl-(2→1)-ß-D-Glc on the O-6 position of →1)-ß-D-Man-(6,4→ of the main chain. The secondary branches linked to the O-4 position of →1)-α-D-Man-(4,3→ with the chain of →1)-α-D-Fuc-(4→1)-α-D-Man. Further, CVP treatment alleviated the symptoms of NAFLD in an HFD-induced mice model. CVP altered gut microbiota, predominantly suppressing microbes associated with bile acids both in the serum and cecal contents. In vitro data showed that CVP reduced HFD-induced hyperlipidemia via farnesoid X receptor. Our results improve our understanding of the mechanisms underlying the cholesterol- and lipid-lowering effects of CVP and indicate that CVP is a promising candidate for NAFLD therapy.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Polyporaceae , Humanos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/química , Micelio/química
6.
Front Neurosci ; 17: 1206491, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37476835

RESUMEN

Objective: Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment (MCI). In light of this, our study aims to examine the efficacy and safety of this treatment approach for patients with MCI. Methods: We conducted a comprehensive search of various databases, including Medline (via PubMed), Cochrane, Embase, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wanfang Database from their inception to November 16, 2022. The selection of studies, risk of bias assessment, and data extraction were carried out independently by two authors. The statistical analysis was performed using STATA. Results: Our meta-analysis included a total of 35 studies with 2,833 patients, published between 2008 and 2022, with intervention durations ranging from 4 weeks to 12 months. However, most of the studies had a high risk of detection bias. Our findings indicated that the combination of donepezil and TCM significantly improved the Montreal Cognitive Assessment (MoCA) score (weighted mean difference [WMD] = 2.79, 95% confidence interval [CI]: 1.82 to 3.75) and the Barthel Index score (WMD = 9.20, 95% CI: 5.39 to 13.00) compared to donepezil alone. However, subgroup analyses showed that the MoCA score did not increase significantly in patients with MCI resulting from cerebrovascular disease (WMD = 1.47, 95% CI: -0.02 to 2.96). Conclusion: The combination of donepezil and TCM may have a more positive effect on cognitive function and activities of daily living in patients with MCI compared to the use of donepezil alone. However, due to the limited quality of the studies included in our analysis, these findings should be interpreted with caution.

7.
Chemosphere ; 331: 138765, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37094721

RESUMEN

In the last few years, coupling heterogeneous photocatalysis with persulfate (PDS) activation process is an efficient approach to generate abundant reactive oxidative species towards organic contaminant removal in water, however, the key role of PDS in photocatalytic process remains ambiguous. Herein, a novel g-C3N4-CeO2 (CN-CeO2) step-scheme (S-scheme) composite was constructed to photo-degrade bisphenol A (BPA) with the presence of PDS under visible irradiation. At 2.0 mM PDS, 0.7 g/L CN-CeO2 and natural pH 6.2, 94.2% of BPA could be eliminated in 60 min under visible light (Vis) illumination. Aside from the previous view of free radical generation, it tends to assume that most of PDS molecules acted as electron sacrificial agents for capturing photo-induced e- to form sulfate ions, greatly improving the charge carrier separation and thus enhancing the oxidation capacity of nonradical hole (h+) for the removal of BPA. Good correlations are further found between the rate constant and descriptor variables (i.e., Hammett constant σ-/σ+ and half-wave potential E1/2), exhibiting selective oxidation for organic pollutants in the Vis/CN-CeO2/PDS system. The study brings more insights into mechanistic understanding of persulfate-enhanced photocatalytic process for addressing water decontamination.


Asunto(s)
Contaminantes Químicos del Agua , Catálisis , Contaminantes Químicos del Agua/química , Luz , Agua
8.
BMC Public Health ; 23(1): 734, 2023 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-37085861

RESUMEN

BACKGROUND: Men who have sex with men and women (MSMW) are the most important bridge population for HIV transmission. Condom use plays an important role for HIV infection. However the predictors for condom ues with females are not well characterized. METHODS: This was a cross-sectional study. Participants were enrolled by four community-based organizations (CBOs) by offline (bathrooms, bars), and online (gay applications, chat room) from April to December 2019. Electronic questionnare was fulfilled after a face-to-face training led by CBOs. We identified predictors of inconsistent condom use with females by creating a risk score based on regression coefficients. We externally validated this score via an independent cross-sectional survey conducted in Zhejiang Province in 2021. A total of 917, 615 MSMW were included in analysis in 2019 and 2021, seperately. RESULTS: Among 917 MSMW, 73.2% reported heterosexual behavior in the prior 6 months and 38.3% reported inconsistent condom use with females (ICUF) over that time. Compared with heterosexual/unsure MSMW, bisexual MSMW reported more male and female sex partners, higher proportion of inconsistent condom use with males, less commercial sex with males (p < 0.05). Four risky predictors of ICUF were identified: Duration of local residence ≦6 months; more than one male partner in the prior 6 months; inconsistent condom use with males in the prior 6 months; and never heard post-exposure prophylaxis (PEP). The proportions of respondents indicating ICUF in the low- (0), medium- (2-4) and high-risk (6-20) groups (according to our risk scoring system) were 11.7% (14/120), 26.9% (96/357), and 78.1% (125/160), respectively (Ptrend < 0.001). In the validation survey, the respective proportions of those reporting ICUF were 13.4% (15/112), 17.8% (24/185) and 87.3% (96/110) (Ptrend < 0.001). CONCLUSIONS: We developed and validated a predictive risk score for ICUF among MSMW; four factors were identified, of which inconsistent condom use with men was the most important. Risk reduction intervention programs should focus on MSM who report inconsistent condom use with males, never heard PEP, having multiple partners and living in local less than 6 months.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Femenino , Humanos , Homosexualidad Masculina , Infecciones por VIH/epidemiología , Estudios Transversales , Trabajo Sexual , Condones , Conducta Sexual , Factores de Riesgo , Parejas Sexuales , Asunción de Riesgos
9.
J Phys Chem Lett ; 14(11): 2750-2757, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36897319

RESUMEN

Biomass ethanol is regarded as a renewable resource but it is not economically viable to transform it to high-value industrial chemicals at present. Herein, a simple, green, and low-cost CuCl2-ethanol complex is reported for ethanol dehydration to produce ethylene and acetal simultaneously with high selectivity under sunlight irradiation. Under N2 atmosphere, the generation rates of ethylene and acetal were 165 and 3672 µmol g-1 h-1, accounting for 100% in gas products and 97% in liquid products, respectively. An outstanding apparent quantum yield of 13.2% (365 nm) and the maximum conversion rate of 32% were achieved. The dehydration reactions start from the photoexcited CuCl2-ethanol complex, and then go through the energy transfer (EnT) and ligand to metal charge transfer (LMCT) mechanisms to produce ethylene and acetal, respectively. The formation energies of the CuCl2-ethanol complex and the key intermediate radicals (e.g., ·OH, CH3CH2·, and CH3CH2O·) were validated to clarify the mechanisms. Different from previous CuCl2-based oxidation and addition reactions, this work is anticipated to supply new insights into the dehydration reaction of ethanol to produce useful chemical feedstocks.

10.
Chem Biodivers ; 20(1): e202200822, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36527339

RESUMEN

The traditional Chinese medicine of fermented medicine may be under the involvement of multiple strains and the interaction between these microorganisms. Liu Shenqu (Massa Medicata Fermentata, MMF) is one of the most widely used fermented medicines, whose potential processing mechanism is still unclear. In this work, UPLC/MS and GNPS methods were employed to rapidly predict chemical compositions in MMF. Moreover, the dynamic changes of strains, chemical compositions and anti-inflammatory activity of MMF during fermentation process were investigated, and subsequently strains-chemical compositions-efficacy interactions were revealed by Pearson correlation analysis and partial least squares regression (PLSR) analysis. As a result, 24 components were identified, and the potential strains including Bacillus, Burkholderia_Caballeronia_Paraburkholderia, Enterobacter, Aspergillus heterocaryoticus, Rhizopus arrhizus, Kazachstania bulderi, which related to the production of anti-inflammatory active ingredients were exposed. These results demonstrated chemical compositions-strains-efficacy interactions during fermentation of MMF, and provide reference for the exploration of the processing mechanism of MMF.


Asunto(s)
Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicina Tradicional China/métodos , Antiinflamatorios/farmacología
11.
Microbiol Spectr ; 10(5): e0207722, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36129301

RESUMEN

CG23-I lineage constitutes the majority of hypervirulent Klebsiella pneumoniae. A diabetic patient suffered six episodes of infections caused by CG23-I K. pneumoniae. A total of nine isolates were collected in 2020. We performed whole-genome sequencing to elucidate the within-patient evolution of CG23-I K. pneumoniae. The maximum pairwise difference among the nine longitudinally collected isolates was five single nucleotide polymorphisms. One of the mutations was at the Asp87 position of GyrA. Four indels were identified, including an initiator tRNAfMet duplication, a tRNAArg deletion, a 7-bp insertion, and a 22-bp deletion. All 9 isolates had the genomic features of CG23-I K. pneumoniae, a chromosome-borne ICEKp10, and a large virulence plasmid. The carriage of a complete set of genes for the biosynthesis of colibactin by ICEKp10 gave the nine isolates an ability to cause DNA damage to RAW264.7 cells. Compared with the initial isolate, the last isolate with an additional copy of initiator tRNAfMet grew faster in a nutrient-limiting condition and exhibited enhanced virulence in BALB/c mice. Collectively, we characterized the within-patient microevolution of CG23-I K. pneumoniae through an in-depth comparison of genome sequences. Using the in vitro experiments and mouse models, we also demonstrated that these genomic alterations endowed the isolates with advantages to pass through in vivo selection. IMPORTANCE CG23-I is a significant lineage of hypervirulent Klebsiella pneumoniae. This study characterizes the within-patient microevolution of CG23-I K. pneumoniae. Selective pressures from continuous use of antibiotics favored point mutations contributing to bacterial resistance to antibiotics. The duplication of an initiator tRNAfMet gene helped CG23-I K. pneumoniae proliferate to reach a maximal population size during infections. For longer persistence inside a human host, the large virulence plasmid evolved with more flexible control of replication through duplication of the iteron-1 region. With the genomic alterations, the last isolate had a growth advantage over the initial isolate and exhibited enhanced virulence in BALB/c mice. This study gives us a deeper understanding of the genome evolution during the within-patient pathoadaptation of CG23-I K. pneumoniae.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Ratones , Animales , Humanos , Klebsiella pneumoniae/genética , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/genética , Infecciones por Klebsiella/microbiología , ARN de Transferencia de Metionina , Reinfección , ARN de Transferencia de Arginina , Genoma Bacteriano/genética , Plásmidos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
12.
Int J Biol Macromol ; 219: 31-43, 2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-35926671

RESUMEN

Zinc(II) phthalocyanine (ZnPc) is a promising photosensitizer in photodynamic therapy (PDT) for melanoma treatment. However, the poor solubility of ZnPc limits its application. To overcome this limitation, heparosan (HP)-based nanoparticles were prepared by anchoring the l-lysine-linked α-linolenic acid branch to the carboxylic acid group to produce amphiphilic conjugates named heparosan with an l-lysine-linked α-linolenic acid branch (HLA). HLA conjugates could self-assemble into spherical nanoparticles in aqueous media and encapsulate ZnPc to form HLA-ZnPc nanoparticles. The cellular uptake of ZnPc could be improved by HLA carriers. These nanoparticles presented excellent photodynamic-mediated toxicity against mouse melanoma cells (B16) by markedly upregulating the intracellular reactive oxygen species (ROS) levels while showing no cytotoxicity to either B16 or normal cells (L02 and HK-2 cells) in the dark. Furthermore, HLA-ZnPc displayed excellent stability in both powder and Roswell Park Memorial Institute (RPMI) 1640 medium, indicating its promise for application in drug delivery and PDT. These results revealed a strategy for HP-based enhancement of ZnPc in PDT efficacy.


Asunto(s)
Melanoma , Nanopartículas , Compuestos Organometálicos , Fotoquimioterapia , Animales , Ácidos Carboxílicos , Línea Celular Tumoral , Disacáridos , Indoles , Isoindoles , Lisina , Melanoma/tratamiento farmacológico , Ratones , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Polvos , Especies Reactivas de Oxígeno , Zinc , Compuestos de Zinc , Ácido alfa-Linolénico
13.
J Glob Antimicrob Resist ; 29: 331-338, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35413451

RESUMEN

OBJECTIVES: A nosocomial salmonellosis outbreak caused by Salmonella enterica serovar Goldcoast occurred in a respiratory care ward (RCW) of a hospital in central Taiwan between December 24, 2020, and January 21, 2021. Ten isolates recovered from 10 RCW residents were resistant to extended-spectrum cephalosporins. The resistance mechanism needs to be investigated. METHODS: Whole-genome sequencing and antimicrobial susceptibility testing were conducted to determine the genetic resistance determinants and the phenotypic resistance in the isolates. RESULTS: Each of the 10 outbreak isolates harbored an IncHI2 plasmid that carried 15 antimicrobial resistance genes aac(3)-IId, aadA22, aph(3')-Ia, aph(6)-Id, arr-2, blaCTX-M-55, blaLAP-2, blaTEM-1, dfrA14, floR, lnu(F), qnrS13, sul2, sul3, tet(A), an efflux pump regulatory gene ramAp and an IncL plasmid carried a blaOXA-48. The outbreak strains were expected to be resistant to numerous antimicrobials, including aminoglycosides, b-lactams /inhibitors, tetracycline, rifamycin, lincosamide, sulfonamides, trimethoprim, phenicols, fluoroquinolones, and carbapenems. Two outbreak isolates displayed higher minimum inhibitory concentrations than the other eight isolates to cefmetazole and carbapenems, which was linked to a deficiency of a major facilitator superfamily transporter in the two isolates. CONCLUSION: The carbapenem-resistant outbreak strains could have been derived from extensively drug-resistant S. enterica Goldcoast strains, which have been a major pathogen in Taiwan since 2018, through the acquisition of a blaOXA-48-carrying plasmid. Special efforts are needed in Taiwan to monitor the spread of extremely resistant strains.


Asunto(s)
Infección Hospitalaria , Infecciones por Salmonella , Salmonella enterica , Antibacterianos/farmacología , Carbapenémicos/farmacología , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Farmacorresistencia Bacteriana Múltiple/genética , Hospitales , Humanos , Salmonella , Infecciones por Salmonella/epidemiología , Serogrupo , Taiwán/epidemiología
14.
Oxid Med Cell Longev ; 2022: 2792348, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35028004

RESUMEN

Identification of innovative therapeutic targets for the treatment of cognitive impairment in Parkinson's disease (PD) is urgently needed. Hydrogen sulfide (H2S) plays an important role in cognitive function. Therefore, this work is aimed at investigating whether H2S attenuates the cognitive impairment in PD and the underlying mechanisms. In the rotenone- (ROT-) established PD rat model, NaHS (a donor of H2S) attenuated the cognitive impairment and promoted microglia polarization from M1 towards M2 in the hippocampus of PD rats. NaHS also dramatically upregulated the Warburg effect in the hippocampus of PD rats. 2-Deoxyglucose (2-DG, an inhibitor of the Warburg effect) abolished NaHS-upregulated Warburg effect in the hippocampus of PD rats. Moreover, the inhibited hippocampal Warburg effect by 2-DG abrogated H2S-excited the enhancement of hippocampal microglia M2 polarization and the improvement of cognitive function in ROT-exposed rats. Our data demonstrated that H2S inhibits the cognitive dysfunction in PD via promoting microglia M2 polarization by enhancement of hippocampal Warburg effect.


Asunto(s)
Disfunción Cognitiva/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Sulfuro de Hidrógeno/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Humanos , Sulfuro de Hidrógeno/farmacología , Masculino , Microglía , Ratas , Ratas Sprague-Dawley
15.
Int J Biol Macromol ; 201: 47-58, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-34998873

RESUMEN

Heparosan, with a linear chain of disaccharide repeating units of â†’ 4) ß-D-glucuronic acid (GlcA) (1 â†’ 4)-α-D-N-acetylglucosamine (GlcNAc) (1→, is a potential starting chemical for heparin synthesis. However, the chemoenzymatic synthesis of single-site sulfated heparosan and its antitumor activity have not been studied. In this study, 2-deacetyl-3-O-sulfo-heparosan (DSH) was prepared successively by the N-deacetylation chemical reaction and enzymatic modification of human 3-O-sulfotransferase-1 (3-OST-1). Structural characterization of DSH was shown the success of the sulfation with the sulfation degree of 0.87. High performance gel permeation chromatography (HPGPC) analysis revealed that DSH had only one symmetrical sharp peak with a molecular weight of 9.6334 × 104 Da. Biological function studies showed that DSH could inhibit tumor cell (A549, HepG2 and HCT116) viability and induce the apoptosis of A549 cells. Further in vitro mechanistic studies showed that DSH may induce apoptosis via the JNK signaling pathway, and the upstream signal of this process may be fibroblast growth factor receptors. These results indicated that DSH could be developed as one of a potential chemical for tumor treatment.


Asunto(s)
Disacáridos , Receptores de Factores de Crecimiento de Fibroblastos , Células A549 , Disacáridos/química , Disacáridos/metabolismo , Humanos , Peso Molecular , Sulfotransferasas/química , Sulfotransferasas/metabolismo
16.
Cell Mol Neurobiol ; 42(3): 777-790, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33058074

RESUMEN

Arachidonic acid (AA), a polyunsaturated fatty acid, is involved in the modulation of neuronal excitability in the brain. Arachidonate lipoxygenase 3 (ALOXE3), a critical enzyme in the AA metabolic pathway, catalyzes the derivate of AA into hepoxilins. However, the expression pattern of ALOXE3 and its role in the brain has not been described until now. Here we showed that the levels of Aloxe3 mRNA and protein kept increasing since birth and reached the highest level at postnatal day 30 in the mouse hippocampus and temporal cortex. Histomorphological analyses indicated that ALOXE3 was enriched in adult hippocampus, somatosensory cortex and striatum. The distribution was restricted to the neurites of function-specific subregions, such as mossy fibre connecting hilus and CA3 neurons, termini of Schaffer collateral projections, and the layers III and IV of somatosensory cortex. The spatiotemporal expression pattern of ALOXE3 suggests its potential role in the modulation of neural excitability and seizure susceptibility. In fact, decreased expression of ALOXE3 and elevated concentration of AA in the hippocampus was found after status epilepticus (SE) induced by pilocarpine. Local overexpression of ALOXE3 via adeno-associated virus gene transfer restored the elevated AA level induced by SE, alleviated seizure severities by increasing the latencies to myclonic switch, clonic convulsions and tonic hindlimb extensions, and decreased the mortality rate in the pilocarpine-induced SE model. These results suggest that the expression of ALOXE3 is a crucial regulator of AA metabolism in brain, and potentially acts as a regulator of neural excitability, thereby controlling brain development and seizure susceptibility.


Asunto(s)
Convulsiones , Estado Epiléptico , Animales , Encéfalo/metabolismo , Hipocampo/metabolismo , Ratones , Pilocarpina , Convulsiones/inducido químicamente , Convulsiones/genética , Convulsiones/metabolismo , Estado Epiléptico/inducido químicamente
17.
Nanomaterials (Basel) ; 13(1)2022 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-36616016

RESUMEN

Due to its environmental cleanliness and high energy density, hydrogen has been deemed as a promising alternative to traditional fossil fuels. Photocatalytic water-splitting using semiconductor materials is a good prospect for hydrogen production in terms of renewable solar energy utilization. In recent years, halide perovskite nanocrystals (NCs) are emerging as a new class of fascinating nanomaterial for light harvesting and photocatalytic applications. This is due to their appealing optoelectronic properties, such as optimal band gaps, high absorption coefficient, high carrier mobility, long carrier diffusion length, etc. In this review, recent progress in halide perovskite NCs for photocatalytic hydrogen evolution is summarized. Emphasis is given to the current strategies that enhance the photocatalytic hydrogen production performance of halide perovskite NCs. Some scientific challenges and perspectives for halide perovskite photocatalysts are also proposed and discussed. It is anticipated that this review will provide valuable references for the future development of halide perovskite-based photocatalysts used in highly efficient hydrogen evolution.

18.
Org Lett ; 23(21): 8477-8481, 2021 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-34661414

RESUMEN

Reported herein is a regioselective difluoromethane sulfonylation or triflylation of resorufin derivatives, which allows easy access to 2-difluoromethane sulfonylated or triflylated resorufin derivatives in good yields. The installation of a difluoromethane sulfonyl group significantly increases the solubility of the chromophore and expands its Stokes shift. A difluoromethane sulfonylated resorufin-based fluorogenic probe proved to be able to image enzyme activity in live cells with a stronger fluorescence signal compared with its resorufin counterpart.

19.
Gut Microbes ; 13(1): 1980348, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34606408

RESUMEN

Sequence type (ST) 11 is one of the major lineages of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although the gastrointestinal (GI) carriage of CRKP predisposes individuals to subsequent infections, little is known for its impact on gut homeostasis. In this study, we investigated the association between ST11 CRKP colonization and colorectal cancer (CRC). Two ST11 CRKP, KPC160111 (KL47) and KPC160132 (KL64), were selected as the representative strains. We used azoxymethane (AOM) and dextran sodium sulfate (DSS) to initiate a colitis-associated CRC model. Both strains established prolonged colonization in the GI tract of the AOM-DSS-treated BALB/c mice and aggravated gut dysbiosis. Under this AOM-DSS-induced setting, ST11 K. pneumoniae colonization significantly promoted the growth and progression of colorectal adenomas to high-grade dysplasia. Numerous crypts were formed inside the enlarged adenomas, in which CD163+ tumor-associated macrophages accumulated. Similarly, ST11 K. pneumoniae also increased the population size of the CD163+ macrophages with the M2 phenotype in the peritoneal cavity of LPS-primed BALB/c mice. When applied to RAW264.7 cells, ST11 K. pneumoniae polarized the macrophages toward an M2 phenotype through the inhibition of IKK-NFκB and the activation of STAT6-KLF4-IL-10. Through the M2-skewing ability, ST11 K. pneumoniae promoted the accumulation of CD163+ macrophages in the adenomatous crypts to create an immunosuppressive niche, which not only accommodated the extended stay for its own sake but also deteriorated colorectal tumorigenesis.


Asunto(s)
Colitis/complicaciones , Neoplasias Colorrectales/microbiología , Klebsiella pneumoniae/fisiología , Animales , Carcinogénesis , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Klebsiella pneumoniae/crecimiento & desarrollo , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Factor de Transcripción STAT6/genética , Factor de Transcripción STAT6/metabolismo
20.
Huan Jing Ke Xue ; 42(10): 4582-4592, 2021 Oct 08.
Artículo en Chino | MEDLINE | ID: mdl-34581100

RESUMEN

Topography not only has an effect on the spatial distribution of pollutants by restricting populations and industrial activities, but also affects the formation, transmission, accumulation, diffusion, and sedimentation of PM2.5. Topography is, therefore, an essential variable for understanding the spatial distribution of PM2.5, especially in basin areas. Based on gridded data and both natural and human indexes, this paper examines orographic effects on the distribution of PM2.5 on the Fen-Wei Plain based on the change point method, regression, the geographical detector method, and bivariate spatial autocorrelation. The results indicate that:① The relief amplitude of the plain is generally lower in its central part than at its edge, which is similar to the attitudinal distribution in this region; ② The distribution of PM2.5 is negatively related to relief amplitude, with high concentrations in central area and lower concentrations at the edge; ③ Based on the geographical detector analysis, PM2.5 patterns in this region are shaped by human factors including population, gross domestic product(GDP), and energy consumption, as well as natural factors including meteorological conditions and vegetation; and ④ Topography has a significant effect on both human and natural factors; an increase of relief amplitude is associated with a decrease in population, GDP, and energy consumption based on power function. Accordingly, temperature goes down linearly; precipitation, relative moisture, and wind speed increase linearly; and the vegetation index increases based on a logarithmic function.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China , Monitoreo del Ambiente , Humanos , Material Particulado/análisis , Análisis Espacial , Viento
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