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1.
J Am Chem Soc ; 146(25): 17023-17031, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38753972

RESUMO

The development of low-temperature lithium metal batteries (LMBs) encounters significant challenges because of severe dendritic lithium growth during the charging/discharging processes. To date, the precise origin of lithium dendrite formation still remains elusive due to the intricate interplay between the highly reactive lithium metal anode and organic electrolytes. Herein, we unveil the critical role of interfacial defluorination kinetics of localized high-concentration electrolytes (LHCEs) in regulating lithium dendrite formation, thereby determining the performance of low-temperature LMBs. We investigate the impact of solvation structures of LHCEs on low-temperature LMBs by employing tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF) as comparative solvents. The combination of comprehensive characterizations and theoretical simulations reveals that the THF-based LHCE featured with a strong solvation strength exhibits fast interfacial defluorination reaction kinetics, thus leading to the formation of an amorphous and inorganic-rich solid-electrolyte interphase (SEI) that can effectively suppress the growth of lithium dendrites. As a result, the highly reversible Li metal anode achieves an exceptional Coulombic efficiency (CE) of up to ∼99.63% at a low temperature of -30 °C, thereby enabling stable cycling of low-temperature LMB full cells. These findings underscore the crucial role of electrolyte interfacial reaction kinetics in shaping SEI formation and provide valuable insights into the fundamental understanding of electrolyte chemistry in LMBs.

2.
Small ; : e2405139, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39129665

RESUMO

In spite of extensive research and appreciable progress, in aqueous zinc-ion batteries, Zn metal anode is struggling with low Zn utility and poor cycling stability. In this study, a 3D "electrochemical welding" composite electrode is designed by introduction of ZnO/C nanofibers film to copper foils as an anode according to pre-electrodeposition active Zn (Zn@ZnO/C-Cu). The flow of Zn2+ through carbon fiber layer is regulated by zincophilic ZnO, promoting homogeneous diffusion of Zn2+ to Cu foil. In subsequent Zn deposition/stripping processes, the hydrophobicity of ZnO/C fiber layer reduces water at the interface of Zn@ZnO/C-Cu and results in uniform electric field significant suppressing growth of Zn dendritic and side reactions. Thus, pre-electrodeposition active Zn electrochemical welds ZnO/C nanofibers and Cu foil collectively provide stable charge/electron transfer and stripping/plating of Zn with low polarization and excellent cycling performance. The assembled symmetrical batteries exhibit stable cycling performance for over 470 h under 20% utilization of Zn at 5 mA cm-2, and an average coulombic efficiency of 99.9% at low negative/positive capacity ratio (N/P = 1) after 1000 cycles in the Zn@ZnO/C-Cu||Na2V6O16·1.5H2O full cell.

3.
Eur Radiol ; 34(1): 662-672, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37535155

RESUMO

OBJECTIVES: To construct a machine learning model for differentiating Parkinson's disease (PD) and multiple system atrophy (MSA) by using multimodal PET/MRI radiomics and clinical characteristics. METHODS: One hundred and nineteen patients (81 with PD and 38 with MSA) underwent brain PET/CT and MRI to obtain metabolic images ([18F]FDG, [11C]CFT PET) and structural MRI (T1WI, T2WI, and T2-FLAIR). Image analysis included automatic segmentation on MRI, co-registration of PET images onto the corresponding MRI. Radiomics features were then extracted from the putamina and caudate nuclei and selected to construct predictive models. Moreover, based on PET/MRI radiomics and clinical characteristics, we developed a nomogram. Receiver operating characteristic (ROC) curves were performed to evaluate the performance of the models. Decision curve analysis (DCA) was employed to access the clinical usefulness of the models. RESULTS: The combined PET/MRI radiomics model of five sequences outperformed monomodal radiomics models alone. Further, PET/MRI radiomics-clinical combined model could perfectly distinguish PD from MSA (AUC = 0.993), which outperformed the clinical model (AUC = 0.923, p = 0.028) in training set, with no significant difference in test set (AUC = 0.860 vs 0.917, p = 0.390). However, no significant difference was found between PET/MRI radiomics-clinical model and PET/MRI radiomics model in training (AUC = 0.988, p = 0.276) and test sets (AUC = 0.860 vs 0.845, p = 0.632). DCA demonstrated the highest clinical benefit of PET/MRI radiomics-clinical model. CONCLUSIONS: Our study indicates that multimodal PET/MRI radiomics could achieve promising performance to differentiate between PD and MSA in clinics. CLINICAL RELEVANCE STATEMENT: This study developed an optimal radiomics signature and construct model to distinguish PD from MSA by multimodal PET/MRI imaging methods in clinics for parkinsonian syndromes, which achieved an excellent performance. KEY POINTS: •Multimodal PET/MRI radiomics from putamina and caudate nuclei increase the diagnostic efficiency for distinguishing PD from MSA. •The radiomics-based nomogram was developed to differentiate between PD and MSA. •Combining PET/MRI radiomics-clinical model achieved promising performance to identify PD and MSA.


Assuntos
Atrofia de Múltiplos Sistemas , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radiômica , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Estudos Retrospectivos
4.
BMC Public Health ; 24(1): 266, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38262984

RESUMO

BACKGROUND: Heavy metal pollution has emerged as a significant concern for human health, prompting increased awareness of its potential adverse effects. While previous research has established a connection between heavy metals and liver function biomarkers, the specific relationship between heavy metals and HBV infection remains unexplored. This cross-sectional study aims to investigate the potential correlations between five blood heavy metals - lead, cadmium, mercury, manganese, and selenium - and the presence of HBsAg, HBsAb, and HBcAb in adults. METHODS: The study utilized data from NHANES 2007-2018. Participants were classified into four groups based on their infectious status, and the association between heavy metals and HBV infection was analyzed using multiple logistic regression and stratification analysis. RESULTS: A total of 8431 participants were included, with 5 436 classified as Susceptible, 1 765 as Vaccinated, 865 as Natural Infection, and 103 as Acute/Chronic HBV Infection. The Vaccinated group exhibited a lower mean age (34.52 ± 14.16 years) compared to the other groups. Statistically significant differences in heavy metal concentrations (except selenium) were observed among the groups (P < 0.001). After adjusting for covariates, lead was significantly associated with HBV infection (Q2: OR 2.37, 95%CI 1.04-5.39; Q3: OR 2.34, 95%CI 1.01-5.40), and positive trends were observed for high blood concentrations of mercury (Q4: OR 3.03, 95%CI 1.31-7.04) and manganese (Q4: OR 2.52, 95%CI 1.20-5.28). Furtherly, the presence of lead reduced the protection of HBsAb (Q2: OR 0.84, 95%CI 0.73-0.97; Q3: OR 0.77, 95%CI 0.66-0.90; Q4: OR 0.83, 95%CI 0.70-0.98). Subgroup analysis indicated that cadmium was associated with an increased risk of HBV infection in Asians (OR 1.36, 95%CI 1.03-1.78) and individuals with a BMI range of 25 to 30 (OR 1.60, 95%CI 1.17-2.18). CONCLUSIONS: The study's findings suggest a correlation between elevated blood Pb concentrations and reduced immunization rates against hepatitis B. Individuals with a positive HBsAg exhibit lower blood Se concentrations and higher blood Hg and Mn concentrations.


Assuntos
Hepatite B , Mercúrio , Metais Pesados , Selênio , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Vírus da Hepatite B , Estudos Transversais , Cádmio , Manganês , Antígenos de Superfície da Hepatite B , Inquéritos Nutricionais , Anticorpos Anti-Hepatite B
5.
COPD ; 21(1): 2363630, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38973373

RESUMO

Chronic obstructive pulmonary disease (COPD) is preventable and requires early screening. The study aimed to examine the clinical values of long non-coding RNA (lncRNA) SNHG5 in COPD diagnosis and prognosis. Out of 160 COPD patients, 80 were in the stable stage and 80 were in the acute exacerbation of COPD stage (AECOPD). SNHG5 expression was detected via qRT-PCR. The survival analysis was conducted using Cox regression analysis and K-M curve. SNHG5 levels significantly reduced in both stable COPD and AECOPD groups compared with the control group, with AECOPD group recording the lowest values. SNHG5 levels were negatively correlated with GOLD stage. Serum SNHG5 can differentiate stable COPD patients from healthy individuals (AUC = 0.805), and can screen AECOPD from stable ones (AUC = 0.910). SNHG5 negatively influenced the release of inflammatory cytokines. For AECOPD patients, those with severe cough and wheezing dyspnea symptoms exhibited the lowest values of SNUG5. Among the 80 AECOPD patients, 16 cases died in the one-year follow-up, all of whom had low levels of SNHG5. SNHG5 levels independently influenced survival outcomes, patients with low SNHG5 levels had a poor prognosis. Thus, lncRNA SNHG5, which is downregulated in patients with COPD (especially AECOPD), can potentially protect against AECOPD and serve as a novel prognostic biomarker for AECOPD.


Assuntos
Progressão da Doença , Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , RNA Longo não Codificante/genética , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos de Casos e Controles , Citocinas/sangue , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Tosse/etiologia , Dispneia/etiologia , Biomarcadores/sangue , Relevância Clínica
6.
BMC Genomics ; 24(1): 81, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810020

RESUMO

Trichosanthes kirilowii Maxim. (TK) is a dioecious plant in the Cucurbitaceae family of which different sexes have separate medicinal uses. We used Illumina high-throughput sequencing technology to sequence miRNAs from male and female flower buds of TK. We performed bioinformatics analysis, miRNA identification, and target gene prediction on the data obtained from sequencing, and association analysis was performed in combination with the results of a previous transcriptome sequencing study. As a result, there were 80 differentially expressed miRNAs (DESs) between the female and male plants (48 upregulated and 32 downregulated in female plants). Moreover, 27 novel miRNAs in DESs were predicted to have 282 target genes, and 51 known miRNAs were predicted to have 3418 target genes. By establishing a regulatory network between miRNAs and target genes, 12 core genes were screened, including 7 miRNAs and 5 target genes. Among them, tkmiR157a-5p, tkmiR156c, tkmiR156_2, and tkmiR156k_2 jointly target the regulation of tkSPL18 and tkSPL13B. These two target genes are specifically expressed in male and female plants, respectively, and are involved in the biosynthesis process of BR, which is closely related to the sex differentiation process of TK. The identification of these miRNAs will provide a reference for the analysis of the sex differentiation mechanism of TK.


Assuntos
Cucurbitaceae , MicroRNAs , Trichosanthes , Trichosanthes/genética , MicroRNAs/genética , Regulação da Expressão Gênica de Plantas , Cucurbitaceae/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos
7.
Chemistry ; 29(3): e202202380, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36210331

RESUMO

Sodium metal batteries (SMBs) have been widely studied owing to their relatively high energy density and abundant resources. However, they still need systematic improvement to fulfill the harsh operating conditions for their commercialization. In this review, we summarize the recent progress in SMBs in terms of sodium anode modification, electrolyte exploration, and cathode design. Firstly, we give an overview of the current challenges facing Na metal anodes and the corresponding solutions. Then, the traditional liquid electrolytes and the prospective solid electrolytes for SMBs are summarized. In addition, insertion- and conversion-type cathode materials are introduced. Finally, an outlook for the future of practical SMBs is provided.

8.
Foodborne Pathog Dis ; 20(4): 158-168, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37062811

RESUMO

Invasive listeriosis is a rare but serious foodborne disease that causes maternal-neonatal, central nervous system, and bloodstream infections. The aim of this study was to assess the whole-genome sequencing (WGS)-based genetic diversity of clinical Listeria monocytogenes isolates over a 7-year period and prove the effect of WGS application in food vehicle investigation. A total of 360 isolates were recovered during 2013 and 2019 through the national listeriosis special surveillance program. Two hundred twenty-six isolates (62.8%) were associated with pregnancy. All isolates belonged to lineage I (214 isolates) or lineage II (146 isolates), with 4 serogroups (46.9% IIb, 39.7% IIa, 12.5% IVb, and 0.8% IIc). All isolates were in 25 clonal complexes (CCs) and 3 singletons, with CC87, CC8, and CC5 being the most common causes of human listeriosis. All clinical isolates were positive for Listeria pathogenicity island 1 (LIPI-1), LIPI-3 was present in 21.4% of isolates and LIPI-4 was detected in 29.2% of isolates. LIPI-4-positive isolates, including CC87, sequence type (ST)619, ST382, CC4, and CC2, have been shown to confer hypervirulence. Fifteen isolates harbored at least one antimicrobial encoding gene, including tet (M), mef (A), msr (D), and dfr (G). The sublineage designations were consistent with CC designations, and 215 distinct cgMLST types (CTs) were classified, the most abundant being CT58 and CT750. In summary, there is a high level of genetic diversity among the clinical isolates. WGS has strengthened listeriosis surveillance and will be implemented for other foodborne bacteria in the National Molecular Tracing Network for Foodborne Disease.


Assuntos
Doenças Transmitidas por Alimentos , Listeria monocytogenes , Listeriose , Recém-Nascido , Humanos , Listeria monocytogenes/genética , Microbiologia de Alimentos , Listeriose/epidemiologia , Listeriose/microbiologia , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , China/epidemiologia
9.
Int J Mol Sci ; 24(8)2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37108503

RESUMO

Actinomycetes are essential sources of numerous bioactive secondary metabolites with diverse chemical and bioactive properties. Lichen ecosystems have piqued the interest of the research community due to their distinct characteristics. Lichen is a symbiont of fungi and algae or cyanobacteria. This review focuses on the novel taxa and diverse bioactive secondary metabolites identified between 1995 and 2022 from cultivable actinomycetota associated with lichens. A total of 25 novel actinomycetota species were reported following studies of lichens. The chemical structures and biological activities of 114 compounds derived from the lichen-associated actinomycetota are also summarized. These secondary metabolites were classified into aromatic amides and amines, diketopiperazines, furanones, indole, isoflavonoids, linear esters and macrolides, peptides, phenolic derivatives, pyridine derivatives, pyrrole derivatives, quinones, and sterols. Their biological activities included anti-inflammatory, antimicrobial, anticancer, cytotoxic, and enzyme-inhibitory actions. In addition, the biosynthetic pathways of several potent bioactive compounds are summarized. Thus, lichen actinomycetes demonstrate exceptional abilities in the discovery of new drug candidates.


Assuntos
Anti-Infecciosos , Líquens , Líquens/química , Ecossistema , Fungos , Antibacterianos/metabolismo , Anti-Infecciosos/farmacologia
10.
Angew Chem Int Ed Engl ; 62(31): e202304411, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37269185

RESUMO

The stable cycling of Mg-metal anodes is limited by several problems, including sluggish electrochemical kinetics and passivation at the Mg surface. In this study, we present a high-entropy electrolyte composed of lithium triflate (LiOTf) and trimethyl phosphate (TMP) co-added to magnesium bis(trifluoromethane sulfonyl)imide (Mg(TFSI)2 /1,2-dimethoxyethane (DME) to significantly improve the electrochemical performance of Mg-metal anodes. The as-formed high-entropy Mg2+ -2DME-OTf- -Li+ -DME-TMP solvation structure effectively reduced the Mg2+ -DME interaction in comparison with that observed in traditional Mg(TFSI)2 /DME electrolytes, thereby preventing the formation of insulating components on the Mg-metal anode and promoting its electrochemical kinetics and cycling stability. Comprehensive characterization revealed that the high-entropy solvation structure brought OTf- and TMP to the surface of the Mg-metal anode and promoted the formation of a Mg3 (PO4 )2 -rich interfacial layer, which is beneficial for enhancing Mg2+ conductivity. Consequently, the Mg-metal anode achieved excellent reversibility with a high Coulombic efficiency of 98 % and low voltage hysteresis. This study provides new insights into the design of electrolytes for Mg-metal batteries.

11.
Angew Chem Int Ed Engl ; 62(50): e202313447, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37885102

RESUMO

Ether-based electrolytes are considered as an ideal electrolyte system for sodium metal batteries (SMBs) due to their superior compatibility with the sodium metal anode (SMA). However, the selection principle of ether solvents and the impact on solid electrolyte interphase formation are still unclear. Herein, we systematically compare the chain ether-based electrolyte and understand the relationship between the solvation structure and the interphasial properties. The linear ether solvent molecules with different terminal group lengths demonstrate remarkably distinct solvation effects, thus leading to different electrochemical performance as well as deposition morphologies for SMBs. Computational calculations and comprehensive characterizations indicate that the terminal group length significantly regulates the electrolyte solvation structure and consequently influences the interfacial reaction mechanism of electrolytes on SMA. Cryogenic electron microscopy clearly reveals the difference in solid electrolyte interphase in various ether-based electrolytes. As a result, the 1,2-diethoxyethane-based electrolyte enables a high Coulombic efficiency of 99.9 %, which also realizes the stable cycling of Na||Na3 V2 (PO4 )3 full cell with a mass loading of ≈9 mg cm-2 over 500 cycles.

12.
J Enzyme Inhib Med Chem ; 37(1): 728-742, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35176963

RESUMO

The linking of ethacrynic acid with ethylenediamine and 1,4-butanediamine gave EDEA and BDEA, respectively, as membrane-permeable divalent pro-inhibitors of glutathione S-transferase (GST). Their divalent glutathione conjugates showed subnanomolar inhibition and divalence-binding to GSTmu (GSTM) (PDB: 5HWL) at ∼0.35 min-1. In cisplatin-resistant SK-OV-3, COC1, SGC7901 and A549 cells, GSTM activities probed by 15 nM BDEA or EDEA revealed 5-fold and 1.0-fold increases in cisplatin-resistant SK-OV-3 and COC1 cells, respectively, in comparison with the susceptible parental cells. Being tolerable by HEK293 and LO2 cells, BDEA at 0.2 µM sensitised resistant SK-OV-3 and COC1 cells by ∼3- and ∼5-folds, respectively, released cytochrome c and increased apoptosis; EDEA at 1.0 µM sensitised resistant SK-OV-3 and A549 cells by ∼5- and ∼7-fold, respectively. EDEA at 1.7 µg/g sensitised resistant SK-OV-3 cells to cisplatin at 3.3 µg/g in nude mouse xenograft model. BDEA and EDEA are promising leads for probing cellular GSTM and sensitising cisplatin-resistant ovarian cancers.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Ácido Etacrínico/farmacologia , Etilenodiaminas/farmacologia , Glutationa Transferase/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Putrescina/farmacologia , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Etacrínico/química , Etilenodiaminas/química , Feminino , Glutationa Transferase/metabolismo , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Putrescina/química , Relação Estrutura-Atividade
13.
Sensors (Basel) ; 22(13)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35808542

RESUMO

Soft sensing technologies offer promising prospects in the fields of soft robots, wearable devices, and biomedical instruments. However, the structural design, fabrication process, and sensing algorithm design of the soft devices confront great difficulties. In this paper, a soft tactile actuator (STA) with both the actuation function and sensing function is presented. The tactile physiotherapy finger of the STA was fabricated by a fluid silica gel material. Before pulse detection, the tactile physiotherapy finger was actuated to the detection position by injecting compressed air into its chamber. The pulse detecting algorithm, which realized the pulse detection function of the STA, is presented. Finally, in actual pulse detection experiments, the pulse values of the volunteers detected by using the STA and by employing a professional pulse meter were close, which illustrates the effectiveness of the pulse detecting algorithm of the STA.


Assuntos
Robótica , Dispositivos Eletrônicos Vestíveis , Dedos , Humanos , Tato
14.
Zhongguo Zhong Yao Za Zhi ; 47(23): 6264-6270, 2022 Dec.
Artigo em Zh | MEDLINE | ID: mdl-36604870

RESUMO

The quality of Chinese medicine is the foundation of the clinical effects and industrial development. Component analysis ensures the consistency and stability of medicinals, but fails to evaluate the clinical efficacy. Bioassay is an analytical method to evaluate the effect of a substance on living organisms, tissues, or cells, which is an optimal option for assessing the quality of Chinese medicine. Bioassay of Chinese medicine starts early but progresses slowly. At the moment, it has attracted the interest of scholars. However, no systematic research is available. This study aims to summarize the research on the application of bioassay in quality evaluation of Chinese medicine, focusing on the application of key techniques and experimental systems in bioassay in heat-clearing and blood-activating and stasis-eliminating Chinese medicine and the common problems. Meanwhile, suggestions were proposed in terms of the association with clinical efficacy and chemical analysis and the status quo of biological assay. This study is expected to promote the study and application of bioassay.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Controle de Qualidade , Bioensaio , Temperatura Alta
15.
Mar Drugs ; 19(8)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34436242

RESUMO

Diketopiperazines are potential structures with extensive biological functions, which have attracted much attention of natural product researchers for a long time. These compounds possess a stable six-membered ring, which is an important pharmacophore. The marine organisms have especially been proven to be a wide source for discovering diketopiperazine derivatives. In recent years, more and more interesting bioactive diketopiperazines had been found from various marine habitats. This review article is focused on the new 2,5-diketopiperazines derived from marine organisms (sponges and microorganisms) reported from the secondary half-year of 2014 to the first half of the year of 2021. We will comment their chemical structures, biological activities and sources. The objective is to assess the merit of these compounds for further study in the field of drug discovery.


Assuntos
Organismos Aquáticos/química , Dicetopiperazinas/química , Humanos , Relação Estrutura-Atividade
16.
Phytother Res ; 35(4): 2133-2144, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33264813

RESUMO

The persistence of hyperglycemia and oxidative stress in diabetic patients ultimately leads to diabetic nephropathy (DN). In this study, we investigated the effect of sulfated polysaccharides (SPS) extracted from Laminaria japonica in relieving DN symptoms. To induce the diabetic model, normal rats were kept on a high-sugar, high-fat diet, then they were injected with streptozocin. Groups of these rats were later treated with SPS and/or protein kinase C (PKC) inhibitor. The analyses performed herein demonstrate that although diabetes significantly decreases the body weights of rats, SPS and inhibitor treatments increase these weights, as well as the ratios of renal to total body weight. Serum biochemical analyses indicate that blood urea nitrogen and serum creatinine levels gradually decrease in the SPS group. In addition, DN symptoms are substantially relieved by SPS and/or inhibitor treatments, as evidenced by histopathological analyses. Changes in the expressions of PKC-α, PKC-ß, P-selectin, nuclear factor kappa B (NF-κB), and p65, detected by immunohistochemistry and western blot assessments, show that SPS regulates diabetic nephropathy via the PKC/NF-κB pathway.


Assuntos
Anticoagulantes/uso terapêutico , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , NF-kappa B/metabolismo , Fragmentos de Peptídeos/metabolismo , Polissacarídeos/uso terapêutico , Proteína Quinase C/metabolismo , Animais , Anticoagulantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/patologia , Regulação para Baixo , Masculino , Polissacarídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
17.
Emerg Infect Dis ; 25(12): 2274-2277, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31742514

RESUMO

During 2013-2017, a total of 211 cases of listeriosis were reported by 64 sentinel hospitals in China to a national foodborne disease surveillance network. The average case-fatality rate was 31.2% for perinatal cases and 16.4% for nonperinatal cases. Sequence types 87 and 8 were the most prevalent types.


Assuntos
Infecção Hospitalar/epidemiologia , Listeriose/epidemiologia , Vigilância de Evento Sentinela , Adulto , China/epidemiologia , Infecção Hospitalar/história , Infecção Hospitalar/microbiologia , Geografia Médica , História do Século XXI , Humanos , Listeria/classificação , Listeria/genética , Listeriose/história , Listeriose/microbiologia , Vigilância da População , Prevalência , Adulto Jovem
18.
Biol Pharm Bull ; 40(12): 2175-2182, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29199240

RESUMO

In this study, the effects of N-acyl taurates (NATs) on the intestinal absorption of curcumin (CUR), a water-insoluble and poorly absorbed compound, were examined in rats. Sodium methyl lauroyl taurate (LMT) and sodium methyl cocoyl taurate (CMT) were the most effective in increasing the solubility and intestinal absorption of CUR. The intestinal membrane toxicity of the NATs was also evaluated by measuring the activity of lactate dehydrogenase (LDH), a toxicity marker. NATs did not increase the activity of LDH, suggesting that they may be safely administered orally. We further elucidated the absorption-enhancing mechanisms of NATs by using Caco-2 cells. In cellular transport studies, LMT and CMT reduced the transepithelial electrical resistance value of Caco-2 cells and increased the transport of 5(6)-carboxyfluorescein and CUR. Hence, the intestinal absorption enhancement by LMT and CMT was attributed to the synergistic effect of higher solubility and greater permeability of the cell layer towards CUR in the presence of the surfactants. In summary, co-administration of CUR with either LMT or CMT is a simple and effective method to enhance oral delivery of CUR.


Assuntos
Curcumina/farmacologia , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Tensoativos/farmacologia , Taurina/análogos & derivados , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Curcuma/química , Curcumina/química , Sinergismo Farmacológico , Impedância Elétrica , Humanos , Mucosa Intestinal/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Ratos , Ratos Wistar , Solubilidade , Taurina/farmacologia
19.
J Enzyme Inhib Med Chem ; 32(1): 968-977, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28718678

RESUMO

AChE and BuChE are druggable targets for the discovery of anti-Alzheimer's disease drugs, while dual-inhibition of these two targets seems to be more effective. In this study, we synthesised a series of novel isoflavone derivatives based on our hit compound G from in silico high-throughput screening and then tested their activities by in vitro AChE and BuChE bioassays. Most of the isoflavone derivatives displayed moderate inhibition against both AChE and BuChE. Among them, compound 16 was identified as a potent AChE/BuChE dual-targeted inhibitor (IC50: 4.60 µM for AChE; 5.92 µM for BuChE). Molecular modelling study indicated compound 16 may possess better pharmacokinetic properties, e.g. absorption, blood-brain barrier penetration and CYP2D6 binding. Taken together, our study has identified compound 16 as an excellent lead compound for the treatment of Alzheimer's disease.


Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Descoberta de Drogas , Isoflavonas/farmacologia , Doença de Alzheimer/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Isoflavonas/síntese química , Isoflavonas/química , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
20.
Mar Drugs ; 15(4)2017 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-28383489

RESUMO

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H2O2-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3ß, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD.


Assuntos
Apoptose/efeitos dos fármacos , Peróxido de Hidrogênio/efeitos adversos , Fosfatidilinositol 3-Quinases/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfatos/farmacologia , Caspases/metabolismo , Linhagem Celular , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
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