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1.
Int J Microbiol ; 2024: 7172386, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590774

RESUMO

Atopic dermatitis is one of the most common dermatologic problems, especially in children. Given the ability of symbiotic microorganisms in modulating the immune system, probiotics administration has been studied in previous research in the management of atopic dermatitis. However, there are conflicting results between studies. In this study, we aimed to assess the effectiveness of mixed probiotics as a treatment option for atopic dermatitis induced by ovalbumin. BALB/c juvenile mice were classified and divided into the ovalbumin group, mixed probiotic group (ovalbumin + LK), and control group. Except for the control group, all mice were sensitized with ovalbumin to establish a model of atopic dermatitis. The mixed probiotics were given by gavage for 14 days. Mice body weight, skin lesions, skin inflammation, ovalbumin-specific Ig, the number of Treg and CD103+DC, and the expression level of PD-1/PD-L1 were examined. The results showed that mixed probiotics can improve body weight and alleviate skin symptoms. Mixed probiotics reduced serum Th2 inflammatory factors, eosinophils, mast cell degranulation, mast cell count, and the expression of ovalbumin-specific immunoglobulin E/G1 and increased the anti-inflammatory cytokine interleukin-10, Treg cells, CD103+DC cells, and the expression level of PD-1/PD-L1. These findings suggest that mixed probiotics could be a viable treatment option for atopic dermatitis and provide insight into the underlying mechanisms involved.

2.
Natl Sci Rev ; 11(5): nwae055, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38577668

RESUMO

Enhancing the quality of junctions is crucial for optimizing carrier extraction and suppressing recombination in semiconductor devices. In recent years, metal halide perovskite has emerged as the most promising next-generation material for optoelectronic devices. However, the construction of high-quality perovskite junctions, as well as characterization and understanding of their carrier polarity and density, remains a challenge. In this study, using combined electrical and spectroscopic characterization techniques, we investigate the doping characteristics of perovskite films by remote molecules, which is corroborated by our theoretical simulations indicating Schottky defects consisting of double ions as effective charge dopants. Through a post-treatment process involving a combination of biammonium and monoammonium molecules, we create a surface layer of n-type low-dimensional perovskite. This surface layer forms a heterojunction with the underlying 3D perovskite film, resulting in a favorable doping profile that enhances carrier extraction. The fabricated device exhibits an outstanding open-circuit voltage (VOC) up to 1.34 V and achieves a certified efficiency of 19.31% for single-junction wide-bandgap (1.77 eV) perovskite solar cells, together with significantly enhanced operational stability, thanks to the improved separation of carriers. Furthermore, we demonstrate the potential of this wide-bandgap device by achieving a certified efficiency of 27.04% and a VOC of 2.12 V in a perovskite/perovskite tandem solar cell configuration.

3.
CNS Neurosci Ther ; 30(4): e14685, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634270

RESUMO

OBJECTIVE: Neuronal precursor cells expressed developmentally down-regulated 4 (Nedd4) are believed to play a critical role in promoting the degradation of substrate proteins and are involved in numerous biological processes. However, the role of Nedd4 in intracerebral hemorrhage (ICH) remains unknown. This study aims to investigate the regulatory role of Nedd4 in the ICH model. METHODS: Male C57BL/6J mice were induced with ICH. Subsequently, the levels of glutathione peroxidase 4 (GPX4), malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, as well as the expression of divalent metal transporter 1 (DMT1) and Nedd4 were assessed after ICH. Furthermore, the impact of Nedd4 overexpression was evaluated through analyses of hematoma area, ferroptosis, and neurobehavioral function. The mechanism underlying Nedd4-mediated degradation of DMT1 was elecidated using immunoprecipitation (IP) after ICH. RESULTS: Upon ICH, the level of DMT1 in the brain increased, but decreased when Nedd4 was overexpressed using Lentivirus, suggesting a negative correlation between Nedd4 and DMT1. Additionally, the degradation of DMT1 was inhibited after ICH. Furthermore, it was found that Nedd4 can interact with and ubiquitinate DMT1 at lysine residues 6, 69, and 277, facilitating the degradation of DMT1. Functional analysis indicated that overexpression of Nedd4 can alleviate ferroptosis and promote recovery following ICH. CONCLUSION: The results demonstrated that ferroptosis occurs via the Nedd4/DMT1 pathway during ICH, suggesting it potential as a valuable target to inhibit ferroptosis for the treatment of ICH.


Assuntos
Ferroptose , Camundongos , Animais , Masculino , Camundongos Endogâmicos C57BL , Hemorragia Cerebral/metabolismo , Ubiquitinação , Encéfalo/metabolismo
4.
Ren Fail ; 46(1): 2327495, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38465879

RESUMO

Diabetic kidney disease (DKD) is a leading factor in end-stage renal disease. The complexity of its pathogenesis, combined with the limited treatment efficacy, necessitates deeper insights into potential causes. Studies suggest that ferroptosis-driven renal tubular damage contributes to DKD's progression, making its counteraction a potential therapeutic strategy. Quercetin, a flavonoid found in numerous fruits and vegetables, has demonstrated DKD mitigation in mouse models, though its protective mechanism remains ambiguous. In this study, we delved into quercetin's potential anti-ferroptotic properties, employing a DKD rat model and high glucose (HG)-treated renal tubular epithelial cell models. Our findings revealed that HG prompted unusual ferroptosis activation in renal tubular epithelial cells. However, quercetin counteracted this by inhibiting ferroptosis and activating NFE2-related factor 2 (Nrf2) expression in both DKD rats and HG-treated HK-2 cells, indicating its renal protective role. Further experiments, both in vivo and in vitro, validated that quercetin stimulates Nrf2. Thus, our research underscores quercetin's potential in DKD treatment by modulating the ferroptosis process via activating Nrf2 in a distinct DKD rat model, offering a fresh perspective on quercetin's protective mechanisms.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Ferroptose , Camundongos , Ratos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Estreptozocina , Fator 2 Relacionado a NF-E2/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo
5.
Rapid Commun Mass Spectrom ; 38(10): e9736, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533576

RESUMO

RATIONALE: Pesticide isomers are widely available in agricultural production and may vary widely in biological activity, potency, and toxicity. Chromatographic and mass spectrometric analysis of pesticide isomers is challenging due to structural similarities. METHODS: Based on liquid chromatography time-of-flight mass spectrometry, identification of cis-trans isomeric pesticides was achieved through retention time, characteristic fragment ions, and relative abundance ratio. Furthermore, theoretical and basic research has been conducted on the differences in characteristic fragment ions and their relative abundance ratios of cis-trans isomers. On the one hand, the cleavage pathways of six cis-trans isomers were elucidated through collision-induced dissociation to explain different fragment ions of the isomers. On the other hand, for those with the same fragment ions but different abundance ratios, energy-resolved mass spectrometry combined with computational chemical density functional theory in terms of kinetics, thermodynamics, and bond lengths was employed to explain the reasons for the differences in characteristic fragment ions and their abundance ratios. RESULTS: A high-resolution mass spectrometry method was developed for the separation and analysis of cis-trans isomers of pesticides in traditional Chinese medicine Radix Codonopsis, and six pesticide isomers were distinguished by retention time, product ions, and relative abundance ratios. The limits of quantification of the six pesticides were up to 10 µg/kg, and the linear ranges of them were 10-200 µg/kg, with coefficients of determination (R2) > 0.99, which demonstrated the good linearity of the six pesticides. The recoveries of the pesticides at spiked concentrations of 10, 20, and 100 µg/kg reached 70-120% with relative standard deviations ≤20%. CONCLUSIONS: It was demonstrated that the application of the method was well suited for accurate qualitative and quantitative analysis for isomers with different structures, which could avoid false-negative results caused by ignoring other isomers effectively.


Assuntos
Resíduos de Praguicidas , Praguicidas , Praguicidas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos , Isomerismo , Íons/análise , Resíduos de Praguicidas/análise
6.
Math Biosci Eng ; 21(1): 1394-1412, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303470

RESUMO

In response to the limited capability of extracting semantic information in knowledge graph completion methods, we propose a model that combines spatial transformation and attention mechanisms (STAM) for knowledge graph embedding. Firstly, spatial transformation is applied to reorganize entity embeddings and relation embeddings, enabling increased interaction between entities and relations while preserving shallow information. Next, a two-dimensional convolutional neural network is utilized to extract complex latent information among entity relations. Simultaneously, a multi-scale channel attention mechanism is constructed to enhance the capture of local detailed features and global semantic features. Finally, the surface-level shallow information and latent information are fused to obtain feature embeddings with richer semantic expression. The link prediction results on the public datasets WN18RR, FB15K237 and Kinship demonstrate that STAM achieved improvements of 8.8%, 10.5% and 6.9% in the mean reciprocal rank (MRR) evaluation metric compared to ConvE, for the respective datasets. Furthermore, in the link prediction experiments on the hydraulic engineering dataset, STAM achieves better experimental results in terms of MRR, Hits@1, Hits@3 and Hits@10 evaluation metrics, demonstrating the effectiveness of the model in the task of hydraulic engineering knowledge graph completion.

7.
CNS Neurosci Ther ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37869777

RESUMO

OBJECTIVE: Microglial polarization plays a critical role in neuroinflammation and may be a potential therapeutic target for ischemic stroke. This study was to explore the role and underlying molecular mechanism of Circular RNA PTP4A2 (circPTP4A2) in microglial polarization after ischemic stroke. METHODS: C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO), while primary mouse microglia and BV2 microglial cells experienced oxygen glucose deprivation/reperfusion (OGD/R) to mimic ischemic conditions. CircPTP4A2 shRNA lentivirus and Colivelin were used to knock down circPTP4A2 and upregulate signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. Microglial polarization was assessed using immunofluorescence staining and Western blot. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were applied to detect the binding between circPTP4A2 and STAT3. RESULTS: The levels of circPTP4A2 were significantly increased in plasma and peri-infarct cortex in tMCAO mice. CircPTP4A2 knockdown reduced infarct volume, increased cortical cerebral blood flow (CBF), and attenuated neurological deficits. It also decreased pro-inflammatory factors levels in peri-infarct cortex and plasma, and increased anti-inflammatory factors concentrations 24 h post-stroke. In addition, circPTP4A2 knockdown suppressed M1 microglial polarization and promoted M2 microglial polarization in both tMCAO mice and OGD/R-induced BV2 microglial cells. Moreover, circPTP4A2 knockdown inhibited the phosphorylation of STAT3 induced by oxygen-glucose deprivation. In contrast, increased phosphorylation of STAT3 partly counteracted the effects of circPTP4A2 knockdown. RNA pull-down and RIP assays further certified the binding between circPTP4A2 and STAT3. CONCLUSION: These results revealed regulatory mechanisms of circPTP4A2 that stimulated neuroinflammation by driving STAT3-dependent microglial polarization in ischemic brain injury. CircPTP4A2 knockdown reduced cerebral ischemic injury and promoted microglial M2 polarization, which could be a novel therapeutic target for ischemic stroke.

8.
J Am Chem Soc ; 145(42): 23076-23087, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37847242

RESUMO

We apply a scientific machine learning (ML) framework to aid the prediction and understanding of nanomaterial formation processes via a joint spectral-kinetic model. We apply this framework to study the nucleation and growth of two-dimensional (2D) perovskite nanosheets. Colloidal nanomaterials have size-dependent optical properties and can be observed in situ, all of which make them a good model for understanding the complex processes of nucleation, growth, and phase transformation of 2D perovskites. Our results demonstrate that this model nanomaterial can form through two processes at the nanoscale: either via a layer-by-layer chemical exfoliation process from lead bromide nanocrystals or via direct nucleation from precursors. We utilize a phenomenological kinetic analysis to study the exfoliation process and scientific machine learning to study the direct nucleation and growth and discuss the circumstances under which it is more appropriate to use phenomenological or more complex machine learning models. Data for both analysis techniques are collected through in situ spectroscopy in a stopped flow chamber, incorporating over 500,000 spectra taken under more than 100 different conditions. More broadly, our research shows that the ability to utilize and integrate traditional kinetics and machine learning methods will greatly assist in the understanding of complex chemical systems.

9.
Sci Rep ; 13(1): 13128, 2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37573447

RESUMO

Middle Permian Qixia Formation in the southwestern region of Sichuan (SW China) has experienced multiphase fluidisation, resulting in an unclear understanding of the reservoir reconstruction effect. In this study, a systematic analysis of the Qi2 member in Wulong Town was carried out by combining field outcrop petrology and geochemistry. The results demonstrated that multiple sets of crystalline dolomite-bioclastic limestone cycles were stacked vertically in the Qi2 member, accompanied by the development of fractures and karst channels. The dolomite was mainly composed of silty-fine dolomite (D1) and recrystallised dolomite (D2). Furthermore, obvious multiphase dolomitic cements (Cd1-Cd2) were present in the fractures and pores. Early karst is known to have lithologic mutation surface development and karst channel development at the top of several secondary cycles. The vadose silt dolomites (Cd1) having karst channels developed dull luminescence under cathode luminescence (CL). Both the geochemical indicators of elements and rare earth element (REE) content indicated dysoxic-oxic environmental conditions. The hydrothermal solution displayed tectonic carniole characteristics in the strata burial stage. Fractures and pores were filled with hydrothermal minerals such as coarse dolomites-saddle dolomites (Cd2, with some caused by recrystallisation of the Cd1 hydrothermal solution) and fluorites. Coarse dolomites-saddle dolomites developed dull-red luminescence with a bright-red rim under CL and their δ18OVPDB values were more negative than those of middle Permian limestone samples. Both the geochemical indicators of elements and REE content indicated the suboxic-anoxic environmental conditions. Karstification had minor constructive impact on the reservoir of the Qi2 member in Baoxing in southwestern Sichuan. Most products of karstification were distributed as fillings in channels. Aside from creating certain networked fractures, the hydrothermal solution was mainly filled with hydrothermal minerals along the fractures, pores and early karst channels. Karst and the hydrothermal solution mainly damaged the middle and upper parts of the middle Permian Qixia Formation in Southwest Sichuan. The impact of episodic fluid on the restoration of the carbonate reservoir was mainly restricted by channels for fluid migration and thickness differences among the reservoir. However, certain thick-layered and massive crystalline dolomite may hold promise for exploration.

10.
Adv Mater ; 35(41): e2304712, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37435622

RESUMO

Incorporating plasticizers is an effective way to facilitate conduction of ions in solid polymer electrolytes (SPEs). However, this conductivity enhancement often comes at the cost of reduced mechanical properties, which can make the electrolyte membrane more difficult to process and increase safety hazards. Here, a novel crosslinking strategy, wherein metal-alkoxy-terminated polymers can be crosslinked by precisely controlling the content of H2 O as an initiator, is proposed. As a proof-of-concept, trimethylaluminum (TMA)-functionalized poly(ethylene oxide) (PEO) is used to demonstrate that ultrafine Al-O nanoclusters can serve as nodes to crosslink PEO chains with a wide range of molecular weights from 10 000 to 8 000 000 g mol-1 . The crosslinked polymer network can incorporate a high concentration of plasticizers, with a total weight percentage over 75%, while still maintaining excellent stretchability (4640%) and toughness (3.87 × 104  kJ m-3 ). The resulting electrolyte demonstrates high ionic conductivity (1.41 mS cm-1 ), low interfacial resistance toward Li metal (48.1 Ω cm2 ), and a wide electrochemical window (>4.8 V vs Li+ /Li) at 30 °C. Furthermore, the LiFePO4 /Li battery shows stable cycle performance with a capacity retention of 98.6% (146.3 mAh g-1 ) over 1000 cycles at 1C (1C = 170 mAh g-1 ) at 30 °C.

11.
ACS Appl Mater Interfaces ; 15(27): 33132-33139, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37379244

RESUMO

High-voltage lithium cobalt oxide (LiCoO2) has the highest volumetric energy density among commercial cathode materials in lithium-ion batteries due to its high working voltage and compacted density. However, under high voltage (4.6 V), the capacity of LiCoO2 fades rapidly due to parasitic reactions of high-valent cobalt with the electrolyte and the loss of lattice oxygen at the interface. In this study, we report a temperature-driven anisotropic doping phenomenon of Mg2+ that results in surface-populated Mg2+ doping to the side of the (003) plane of LiCoO2. Mg2+ dopants enter the Li+ sites, lower the valence state of Co ions with less hybridization between the O 2p and Co 3d orbitals, promote the formation of surface Li+/Co2+ anti-sites, and suppress lattice oxygen loss on the surface. As a result, the modified LiCoO2 demonstrates excellent cycling performance under 4.6 V, reaching an energy density of 911.2 Wh/kg at 0.1C and retaining 92.7% (184.3 mAh g-1) of its capacity after 100 cycles at 1C. Our results highlight a promising avenue for enhancing the electrochemical performance of LiCoO2 by anisotropic surface doping with Mg2+.

12.
Ann Clin Transl Neurol ; 10(8): 1481-1492, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37350305

RESUMO

OBJECTIVE: Accumulating studies have shown that circulating circular RNAs (circRNAs) represent novel biomarkers for many human diseases. We investigated whether plasma circPTP4A2 and circTLK2 levels are associated with stroke severity, infarct volume, stroke etiology, and functional outcome in acute ischemic stroke (AIS) patients. METHODS: We applied quantitative real-time PCR (qPCR) to measure plasma circPTP4A2 and circTLK2 levels of 236 AIS patients within 72 h of symptoms onset and 136 healthy controls. We further assessed the National Institutes of Health Stroke Scale (NIHSS), infarct size, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and the 90-day modified Rankin scale (mRS) for each patient. RESULTS: At admission, plasma circPTP4A2 and circTLK2 levels in patients with moderate to severe stroke were significantly higher compared to those with mild stroke. Logistic regression and receiver-operating characteristic (ROC) curve analyses indicated that they might function as predictive biomarkers for moderate to severe stroke. We also observed a medium positive correlation between these two circRNAs and NIHSS. Plasma circPTP4A2 and circTLK2 levels were slight positively correlated with cerebral infarct volume only in anterior circulation infarction (ACI) patients. Levels of both circPTP4A2 and circTLK2 were closely related with large artery atherosclerosis (LAA) stroke. Moreover, changes within 7 days after admission in circPTP4A2 and circTLK2 were able to predict unfavorable clinical outcome 90 days after AIS. INTERPRETATION: These results demonstrate that plasma circPTP4A2 and circTLK2 strongly correlated with severity, subtypes and prognosis of AIS, and they could serve as promising biomarkers.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Estados Unidos , Humanos , AVC Isquêmico/complicações , RNA Circular/genética , Acidente Vascular Cerebral/diagnóstico , Biomarcadores , Infarto/complicações
13.
Anal Methods ; 15(17): 2121-2131, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37144343

RESUMO

The safety of traditional Chinese medicine (TCM) has garnered considerable interest worldwide. In this study, a high-throughput method for the determination of 255 pesticide residues in decoctions of Radix Codonopsis and Angelica sinensis was developed using liquid chromatography-time-of-flight/mass spectrometry. The methodological verification demonstrated the accuracy and reliability of this method. The frequently detected pesticides in Radix Codonopsis and Angelica sinensis were determined to build a correlation between pesticide properties and the transfer rate of pesticide residues in their decoctions. Water solubility (WS) with a higher correlation coefficient (R) made a significant contribution to the accuracy of the transfer rate prediction model. The regression equations for Radix Codonopsis and Angelica sinensis were T = 13.64 log WS + 10.56 with a correlation coefficient (R) of 0.8617 and T = 10.66 log WS + 25.48 with a correlation coefficient (R) of 0.8072, respectively. This study provides preliminary data on the potential risk of exposure to pesticide residues in Radix Codonopsis and Angelica sinensis decoctions. Furthermore, as a case study on root TCM, this approach may serve as a model for other TCMs.


Assuntos
Angelica sinensis , Codonopsis , Medicamentos de Ervas Chinesas , Resíduos de Praguicidas , Praguicidas , Angelica sinensis/química , Reprodutibilidade dos Testes , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida , Espectrometria de Massas em Tandem
14.
Front Pediatr ; 11: 1074429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846162

RESUMO

Background and objectives: The benefits of physical activity (PA) for asthmatic children were increasingly recognized, and as the design of studies on PA and asthma has become more refined in recent years, the latest evidence needed to be updated. We performed this meta-analysis to synthesize the evidence available from the last 10 years to update the effects of PA in asthmatic children. Methods: A systematic search was conducted in three databases, PubMed, Web of Science, and Cochrane Library. Randomized controlled trials were included, and two reviewers independently conducted the inclusion screening, data extraction, and bias assessment. Results: A total of 9 studies were included in this review after 3,919 articles screened. PA significantly improved the forced vital capacity (FVC) (MD 7.62; 95% CI: 3.46 to 11.78; p < 0.001), and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) (MD 10.39; 95% CI: 2.96 to 17.82; p = 0.006) in lung function. There was no significant difference in forced expiratory volume in the first second (FEV1) (MD 3.17; 95% CI: -2.82 to 9.15; p = 0.30) and fractional exhaled nitric oxide (FeNO) (MD -1.74; 95% CI: -11.36 to 7.88; p = 0.72). Also, PA significantly improved the quality of life as assessed by the Pediatric Asthma Quality of Life Questionnaire (all items p < 0.05). Conclusions: This review suggested that PA could improve FVC, FEF25-75, and quality of life in asthmatic children, but there was insufficient evidence of improvement in FEV1 and airway inflammation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022338984.

15.
Pharmaceutics ; 16(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38258056

RESUMO

Local chemotherapy is an alternative therapeutic strategy that involves direct delivery of drugs to the tumor site. This approach avoids adverse reactions caused by the systemic distribution of drugs and enhances the tumor-suppressing effect by concentrating the drugs at the tumor site. Drug-loaded microspheres are injectable sustained-release drug carriers that are highly suitable for local chemotherapy. However, a complex preparation process is one of the main technical difficulties limiting the development of microsphere formulations. In this study, core-shell structured microspheres loaded with paclitaxel (PTX; with a core-shell structure, calcium alginate outer layer, and a poly (lactic acid-co-glycolic acid) copolymer inner layer, denoted as PTX-CA/PLGA-MS) were prepared using coaxial electrostatic spray technology and evaluated in vitro and in vivo. PTX-CA/PLGA-MS exhibited a two-stage drug release profile and enhanced anti-tumor effect in animal tumor models. Importantly, the preparation method reported in this study is simple and reduces the amount of organic solvent(s) used substantially.

16.
J Ethnopharmacol ; 298: 115632, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35964821

RESUMO

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Pushen capsule is a traditional Chinese medicine compound functioning as 'stimulating blood circulation to remove blood stasis', which widely used to treat hyperlipidemia. Recent clinical research showed that Pushen capsule ameliorated cognitive function in patients with vascular mild cognitive impairment. AIM OF THE STUDY: Explore the potential mechanism of Pushen capsule in vascular dementia (VaD) using network pharmacology analysis and experimental verification. MATERIALS AND METHODS: Active ingredients and their related targets of Pushen capsule, and VaD-related targets were searched in public databases. Core targets, potential functions and mechanisms of Pushen capsule on VaD were predicted by protein-protein interaction (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were conducted to demonstrate the potential mechanisms of Pushen capsule in the treatment of VaD. RESULTS: In total, 155 active ingredients, 273 related targets of Pushen capsule, and 1035 VaD-related targets were selected from the public databases. 147 common targets of Pushen capsule against VaD were obtained. The PPI network, GO and KEGG enrichment analyses revealed that some core targets and signaling pathways are related to inflammation. The experimental results showed that Pushen capsule treatment largely alleviated hippocampal glial activation, accelerated the polarization of activated microglia from the M1 to the M2 phenotype and reduced associated inflammatory factor expression to protect against VaD-induced neuronal loss, synaptic protein reduction and cognitive defects in a dose-dependent manner. Moreover, Pushen capsule reduced the mRNA expression of NF-κB p65; and STAT1. CONCLUSION: Our study demonstrates that Pushen capsule alleviates hippocampal neuroinflammation to protect against VaD-induced cognitive impairment in a dose-dependent manner. The neuroprotective effect of Pushen capsule on VaD might be regulated by the NF-κB; and JAK-STAT pathway.


Assuntos
Demência Vascular , Medicamentos de Ervas Chinesas , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Janus Quinases , Simulação de Acoplamento Molecular , NF-kappa B , Farmacologia em Rede , Fatores de Transcrição STAT , Transdução de Sinais
17.
Front Endocrinol (Lausanne) ; 13: 917356, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937793

RESUMO

Increasing evidence suggests that aldosterone (Aldo) plays an essential role in vascular calcification which is a serious threat to cardiovascular disease (CVD) developed from chronic kidney disease (CKD). However, the exact pathogenesis of vascular calcification is still unclear. First, we established CKD-associated vascular calcification mice model and knockout mice model to investigate the causal relationship between allograft inflammatory factor 1 (AIF-1) and vascular calcification. Then, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) co-culture experiments were performed to further explore the mechanisms of calcification. The results of the Aldo intervention mice model and transgenic mice model showed that Aldo could cause calcification by increasing the AIF-1 level. The results of in vitro co-culture model of ECs and VSMCs showed that AIF-1 silence in ECs may alleviate Aldo-induced calcification of VSMCs. In conclusion, our study indicated that Aldo may induce vascular calcification related to chronic renal failure via the AIF-1 pathway which may provide a potential therapeutic target.


Assuntos
Insuficiência Renal Crônica , Calcificação Vascular , Aldosterona/metabolismo , Animais , Técnicas de Cocultura , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Camundongos , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/induzido quimicamente
18.
J Inflamm Res ; 15: 4087-4104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873383

RESUMO

Background and Purpose: Accumulating evidence suggests that circular RNAs (circRNAs) are involved in immune and inflammatory processes after acute ischemic stroke (AIS). However, the roles of circRNA-mediated competing endogenous RNA (ceRNA) in modulating immune inflammation of AIS have not yet been determined. This study aimed to construct a circRNA-mediated immune-related ceRNA network and identify novel circRNAs in AIS. Methods: Microarray data were downloaded from the GEO database and further analysed by R software. Then, we constructed a circRNA-mediated ceRNA network based on interaction information from the bioinformatics database. A topological property analysis of the ceRNA network was conducted to screen novel circRNAs. Finally, we further applied quantitative real-time polymerase chain reaction (qRT-PCR) to two independent sets. Results: We constructed an AIS immune-related ceRNA (AISIRC) network containing immune-related genes (IRGs), miRNAs, and circRNAs. Additionally, we extracted the subnetwork from the AISIRC network and screened six immune-related circRNAs. After identification and validation, we finally confirmed that plasma levels of circPTP4A2 and circTLK2 were significantly increased in AIS patients compared with both healthy control subjects (HCs) and transient ischemic attack (TIA) patients. Logistic regression and receiver-operating characteristic (ROC) curve analyses demonstrated that these two circRNAs may function as predictive and discriminative biomarkers for AIS. We also confirmed that plasma levels of circPTP4A2 were elevated in TIA patients compared with HCs and might be an independent risk factor for predicting TIA. Longitudinal analysis of circRNA expression up to 90 days after AIS indicated that the ability of circPTP4A2 and circTLK2 to monitor AIS dynamics was highly desirable. Conclusion: In summary, the circRNA-mediated immune-related ceRNA network was successfully constructed, and two circulating circRNAs (circPTP4A2 and circTLK2) improved sensitivity for the diagnosis of AIS and could be considered diagnostic biomarkers.

19.
J Infect Chemother ; 28(11): 1464-1470, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35850403

RESUMO

INTRODUCTION: Medication persistence has rarely been studied for integrase strand transfer inhibitor (INSTI)-based regimens among patients living HIV (PLWH) in Asia. This study investigated medication persistence for newly prescribed INSTI-based regimens in Japan by comparing single-tablet regimens (STRs) versus multiple-tablet regimens (MTRs), based on the Medical Data Vision database. METHODS: Adult PLWH with ≥2 claims for antiretroviral therapy (ART) of interest between 1 January 2017 and 30 June 2018 were included if they had a ≥3-month continuous enrolment prior to the index date and a ≥6-month follow-up after the index date. Medication persistence was measured as the duration from initiation to discontinuation of the prescribed INSTI-based regimen. RESULTS: Overall, 487 patients were included, with 220 in the STR cohort and 267 in the MTR cohort. Persistence was longer in the STR cohort than in the MTR cohort (mean days on the index regimens: 384.2 vs. 317.3, P < 0.001). MTRs were associated with a higher risk of discontinuation than STRs (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.18-2.52; P = 0.005). Other factors that were associated with discontinuation were backbone (emtricitabine/tenofovir disoproxil fumarate vs. emtricitabine/tenofovir alafenamide: HR, 5.64; 95% CI, 3.68-8.66; P < 0.001), third agent (raltegravir vs. elvitegravir/cobicistat: HR, 2.06; 95% CI, 1.10-3.86; P = 0.024), age (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and the number of non-ART index medications (HR, 1.16; 95% CI, 1.12-1.21; P < 0.001). CONCLUSIONS: Among PLWH newly prescribed an INSTI-based regimen in Japan, STRs were associated with longer persistence than MTRs.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , HIV-1 , Adulto , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Humanos , Japão , Adesão à Medicação , Comprimidos/uso terapêutico
20.
Biochem Biophys Res Commun ; 614: 63-69, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35569377

RESUMO

Inflammation and glomerular endothelial dysfunction promote diabetic kidney disease (DKD) progression, but the mechanisms are not fully understood. Allograft inflammatory factor-1 (AIF-1) is a protein that regulates inflammatory reactions and immune responses. This study aimed to explore the mechanism of AIF-1 in a DKD animal model and mouse renal glomerular endothelial cells (MRGECs). We injected AIF-1-shRNA into the tail vein to knockdown AIF-1 in db/db mice. Metabolic index, renal pathological changes and inflammatory factors were measured in each group. Lentiviral transfection was used to overexpress AIF-1 in MRGECs. Inflammatory factors, oxidative stress and nuclear factor-κB (NF-κB) pathway-related proteins were examined. AIF-1 expression was upregulated in glomerular endothelial cells in renal tissues of db/db mice. Knockdown of AIF-1 reversed kidney injury and renal inflammation in db/db mice. In a 30 mM high-glucose environment, overexpression of AIF-1 in MRGECs activated the NF-κB pathway and induced inflammation and oxidative stress. Moreover, this damage could be attenuated by the addition of an NF-κB inhibitor (BAY 11-7082). In conclusion, AIF-1 facilitates glomerular endothelial cell inflammation and oxidative stress in DKD via the NF-κB signaling pathway. Our results provide evidence for the molecular mechanism of DKD and may offer a potential target for DKD treatment.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Nefropatias Diabéticas , Inflamação/metabolismo , Proteínas dos Microfilamentos/metabolismo , Aloenxertos , Animais , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Células Endoteliais/metabolismo , Inflamação/patologia , Rim/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Estresse Oxidativo
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