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1.
PLoS One ; 19(5): e0302386, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38713669

RESUMO

BACKGROUND: The purpose of this study was to evaluate the relationship between hyperuricemia and the risks of all-cause mortality and cardiovascular disease (CVD) mortality in patients with osteoarthritis (OA). METHODS: A retrospective cohort study was performed on 3,971 patients using data from the National Health and Nutrition Examination Survey database between 1999 and 2018. OA was diagnosed through specific questions and responses. The weighted COX regression models were used to explore the factors associated with all-cause mortality/CVD mortality in OA patients. Subgroup analyses were conducted based on age, gender, hypertension, dyslipidemia, CVD, and chronic kidney disease (CKD). Hazard ratio (HR) and 95% confidence interval (95% CI) were measured as the evaluation indexes. RESULTS: During the duration of follow-up time (116.38 ± 2.19 months), 33.69% (1,338 patients) experienced all-cause mortality, and 11.36% (451 patients) died from CVD. Hyperuricemia was associated with higher risks of all-cause mortality (HR: 1.22, 95% CI: 1.06-1.41, P = 0.008) and CVD mortality (HR: 1.32, 95% CI: 1.02-1.72, P = 0.036) in OA patients. Subgroup analyses showed that hyperuricemia was related to the risk of all-cause mortality in OA patients aged >65 years (HR: 1.17, 95% CI: 1.01-1.36, P = 0.042), in all male patients (HR: 1.41, 95% CI: 1.10-1.80, P = 0.006), those diagnosed with hypertension (HR: 1.17, 95% CI: 1.01-1.37, P = 0.049), dyslipidemia (HR: 1.18, 95% CI: 1.01-1.39, P = 0.041), CVD (HR: 1.30, 95% CI: 1.09-1.55, P = 0.004), and CKD (HR: 1.31, 95% CI: 1.01-1.70, P = 0.046). The association between hyperuricemia and a higher risk of CVD mortality was found in OA patients aged ≤ 65 years (HR: 1.90, 95% CI: 1.06-3.41, P = 0.032), who did not suffer from diabetes (HR: 1.36, 95% CI: 1.01-1.86, P = 0.048), who did not suffer from hypertension (HR: 2.56, 95% CI: 1.12-5.86, P = 0.026), and who did not suffer from dyslipidemia (HR: 2.39, 95% CI: 1.15-4.97, P = 0.020). CONCLUSION: These findings emphasize the importance of monitoring serum uric acid levels in OA patients for potentially reducing mortality associated with the disease.


Assuntos
Doenças Cardiovasculares , Hiperuricemia , Inquéritos Nutricionais , Osteoartrite , Humanos , Hiperuricemia/complicações , Hiperuricemia/mortalidade , Hiperuricemia/epidemiologia , Masculino , Feminino , Osteoartrite/mortalidade , Osteoartrite/complicações , Osteoartrite/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/complicações , Fatores de Risco , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Bases de Dados Factuais , Modelos de Riscos Proporcionais , Hipertensão/complicações , Hipertensão/mortalidade , Hipertensão/epidemiologia , Adulto , Dislipidemias/mortalidade , Dislipidemias/complicações , Dislipidemias/epidemiologia
2.
Inflammation ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739342

RESUMO

In this study, we used data-independent acquisition-mass spectrometry (DIA-MS) to analyze the serum proteome in psoriasis vulgaris (PsO). The serum proteomes of seven healthy controls and eight patients with PsO were analyzed using DIA-MS. Weighted gene co-expression network analysis was used to identify differentially expressed proteins (DEPs) that were closely related to PsO. Hub proteins of PsO were also identified. The Proteomics Drug Atlas 2023 was used to predict candidate hub protein drugs. To confirm the expression of the candidate factor, protein tyrosine phosphatase receptor S (PTPRS), in psoriatic lesions and the psoriatic keratinocyte model, immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blotting were performed. A total of 129 DEPs were found to be closely related to PsO. The hub proteins for PsO were PVRL1, FGFR1, PTPRS, CDH2, CDH1, MCAM, and THY1. Five candidate hub protein drugs were identified: encorafenib, leupeptin, fedratinib, UNC 0631, and SCH 530348. PTPRS was identified as a common pharmacological target for these five drugs. PTPRS knockdown in keratinocytes promoted the proliferation and expression of IL-1α, IL-1ß, IL-23A, TNF-α, MMP9, CXCL8, and S100A9. PTPRS expression was decreased in PsO, and PTPRS negatively regulated PsO. PTPRS may be involved in PsO pathogenesis through the inhibition of keratinocyte proliferation and inflammatory responses and is a potential treatment target for PsO.

3.
Front Oncol ; 14: 1412682, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711852
4.
J Agric Food Chem ; 72(19): 11221-11229, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703356

RESUMO

Liposcelis bostrychophila, commonly known as booklouse, is an important stored-product pest worldwide. Studies have demonstrated that booklices have developed resistance to several insecticides. In this study, an integument esterase gene, LbEST-inte4, with upregulated expression, was characterized in L. bostrychophila. Knockdown of LbEST-inte4 resulted in a substantial increase in the booklice susceptibility to malathion. Overexpression of LbEST-inte4 in Drosophila melanogaster significantly enhanced its malathion tolerance. Molecular modeling and docking analysis suggested potential interactions between LbEST-inte4 and malathion. When overexpressed LbEST-inte4 in Sf9 cells, a notable elevation in esterase activity and malathion tolerance was observed. HPLC analysis indicated that the LbEST-inte4 enzyme could effectively degrade malathion. Taken together, the upregulated LbEST-inte4 appears to contribute to malathion tolerance in L. bostrychophila by facilitating the depletion of malathion. This study elucidates the molecular mechanism underlying malathion detoxification and provides the foundations for the development of effective prevention and control measures against psocids.


Assuntos
Esterases , Proteínas de Insetos , Insetos , Inseticidas , Malation , Animais , Malation/metabolismo , Malation/química , Malation/toxicidade , Malation/farmacologia , Inseticidas/metabolismo , Inseticidas/química , Inseticidas/farmacologia , Esterases/metabolismo , Esterases/genética , Esterases/química , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Insetos/efeitos dos fármacos , Resistência a Inseticidas/genética , Inativação Metabólica , Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/metabolismo
5.
J Agric Food Chem ; 72(20): 11493-11502, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38738816

RESUMO

Cacumen platycladi (CP) is a frequently used traditional Chinese medicine to treat hair loss. In this study, CP fermented by Lactiplantibacillus plantarum CCFM1348 increased the proliferation of human dermal papilla cells. In an in vivo assay, compared to nonfermented CP, postbiotics (fermented CP) and synbiotics (live bacteria with nonfermented CP) promoted hair growth in mice. The Wnt/ß-catenin signaling pathway plays crucial roles in the development of hair follicles, including growth cycle restart and maintenance. Both postbiotics and synbiotics upregulated ß-catenin, a major factor of the Wnt/ß-catenin signaling pathway. Postbiotics and synbiotics also increased the vascular endothelial growth factor expression and decreased the BAX/Bcl2 ratio in the dorsal skin of mice. These results suggest that fermented CP by L. plantarum CCFM1348 may promote hair growth through regulating the Wnt/ß-catenin signaling pathway, promoting the expression of growth factors and reducing apoptosis.


Assuntos
Cabelo , Via de Sinalização Wnt , Animais , Camundongos , Cabelo/metabolismo , Cabelo/crescimento & desenvolvimento , Cabelo/química , Humanos , Via de Sinalização Wnt/efeitos dos fármacos , Biotransformação , Fermentação , beta Catenina/metabolismo , beta Catenina/genética , Masculino , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folículo Piloso/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/crescimento & desenvolvimento
6.
Mol Ecol ; : e17386, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751195

RESUMO

One of the key goals of ecology is to understand how communities are assembled. The species co-existence theory suggests that community ß-diversity is influenced by species pool and community assembly processes, such as environmental filtering, dispersal events, ecological drift and biotic interactions. However, it remains unclear whether there are similar ß-diversity patterns among different soil microbial groups and whether all these mechanisms play significant roles in mediating ß-diversity patterns. By conducting a broad survey across Chinese deserts, we aimed to address these questions by investing biological soil crusts (biocrusts). Through amplicon-sequencing, we acquired ß-diversity data for multiple microbial groups, that is, soil total bacteria, diazotrophs, phoD-harbouring taxa, and fungi. Our results have shown varying distance decay rates of ß-diversity across microbial groups, with soil total bacteria showing a weaker distance-decay relationship than other groups. The impact of the species pool on community ß-diversity varied across microbial groups, with soil total bacteria and diazotrophs being significantly influenced. While the contributions of specific assembly processes to community ß-diversity patterns varied among different microbial groups, significant effects of local community assembly processes on ß-diversity patterns were consistently observed across all groups. Homogenous selection and dispersal limitation emerged as crucial processes for all groups. Precipitation and soil C:P were the key factors mediating ß-diversity for all groups. This study has substantially advanced our understanding of how the communities of multiple microbial groups are structured in desert biocrust systems.

7.
Mater Horiz ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563639

RESUMO

Neuromorphic computing, which mimics biological neural networks, is widely regarded as the optimal solution for addressing the limitations of traditional von Neumann computing architecture. In this work, an adjustable multistage resistance switching ferroelectric Bi2FeCrO6 diode artificial synaptic device was fabricated using a sol-gel method with a simple process. The device exhibits nonlinearity in its electrical characteristics, demonstrating tunable multistage resistance switching behavior and a strong ferroelectric diode effect through the manipulation of ferroelectric polarization. One of its salient advantages resides in its capacity to dynamically regulate its polarization state in response to an external electric field, thereby facilitating the fine-tuning of synaptic connection strength while maintaining synaptic stability. The device is capable of accurately simulating the fundamental properties of biological synapses, including long/short-term plasticity, paired-pulse facilitation, and spike-timing-dependent plasticity. Additionally, the device exhibits a distinctive photoelectric response and is capable of inducing synaptic plasticity by light signal activation. The utilization of a femtosecond laser for the scrutiny of carrier transport mechanisms imparts profound insights into the intricate dynamics governing the optical memory effect. Furthermore, utilizing a convolutional neural network (CNN) architecture, the recognition accuracy of the MNIST and fashion MNIST datasets was improved to 95.6% and 78%, respectively, through the implementation of improved random adaptive algorithms. These findings present a new opportunity for utilizing Bi2FeCrO6 materials in the development of artificial synapses for neuromorphic computation.

8.
Heliyon ; 10(7): e28885, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596021

RESUMO

Purpose: This study aimed to investigate the performance of deep learning algorithms in the opportunistic screening for primary angle-closure disease (PACD) using combined anterior segment parameters. Methods: This was an observational, cross-sectional hospital-based study. Patients with PACD and healthy controls who underwent comprehensive eye examinations, including gonioscopy and anterior segment optical coherence tomography (ASOCT) examinations under both light and dark conditions, were consecutively enrolled from the Department of Ophthalmology at the Beijing Tongren Hospital between November 2020 and June 2022. The anterior chamber, anterior chamber angle, iris, and lens parameters were assessed using ASOCT. To build the prediction models, backward logistic regression was utilized to select the variables to discriminate patients with PACD from normal participants, and the area under the receiver operating characteristic curve was used to evaluate the efficacy of the opportunistic screening. Results: The data from 199 patients (199 eyes) were included in the final analysis and divided into two groups: PACD (109 eyes) and controls (90 eyes). Angle opening distance at 500 µm, anterior chamber area, and iris curvature measured in the light condition were included in the final prediction models. The area under the receiver operating characteristic curve was 0.968, with a sensitivity of 91.74 % and a specificity of 91.11 %. Conclusion: ASOCT-based algorithms showed excellent diagnostic performance in the opportunistic screening for PACD. These results provide a promising basis for future research on the development of an angle-closure probability scoring system for PACD screening.

9.
Front Neurosci ; 18: 1344235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560045

RESUMO

Introduction: Migraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI). Methods and analysis: In this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited. The 96 female MWoA participants will be randomized into three groups: Group A (CAT group), Group B [ipsilateral acupuncture (IAT) group], and Group C (sham CAT group) in a 1:1:1 allocation ratio. Each group will receive 30 min of treatment every other day, three times a week, for 8 weeks, followed by an 8-week follow-up period. The primary outcome is the intensity of the migraine attack. Data will be collected at baseline (week 0), at the end of the 8-week treatment period (weeks 1-8), and during the 8-week follow-up (weeks 9-16). Adverse events will be recorded. Multimodal MRI scans will be conducted at baseline and after 8-week treatment. Discussion: This study hypothesized that CAT may treat MWoA by restoring pathological alterations in brain neural activity, particularly by restoring cross-integrated functional connectivity with periaqueductal gray (PAG) as the core pathological brain region. The findings will provide scientific evidence for CAT in the treatment of MWoA. Ethics and dissemination: The Medical Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine has given study approval (approval no. 2022-006). This trial has been registered with the Chinese Clinical Trials Registry (registration no. ChiCTR2300069456). Peer-reviewed papers will be used to publicize the trial's findings. Clinical trial registration: https://clinicaltrials.gov/, identifier ChiCTR2300069456.

10.
Nanomaterials (Basel) ; 14(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38607116

RESUMO

Compared with purely electrical neuromorphic devices, those stimulated by optical signals have gained increasing attention due to their realistic sensory simulation. In this work, an optoelectronic neuromorphic device based on a photoelectric memristor with a Bi2FeCrO6/Al-doped ZnO (BFCO/AZO) heterostructure is fabricated that can respond to both electrical and optical signals and successfully simulate a variety of synaptic behaviors, such as STP, LTP, and PPF. In addition, the photomemory mechanism was identified by analyzing the energy band structures of AZO and BFCO. A convolutional neural network (CNN) architecture for pattern classification at the Mixed National Institute of Standards and Technology (MNIST) was used and improved the recognition accuracy of the MNIST and Fashion-MNIST datasets to 95.21% and 74.19%, respectively, by implementing an improved stochastic adaptive algorithm. These results provide a feasible approach for future implementation of optoelectronic synapses.

11.
Nat Commun ; 15(1): 3115, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600102

RESUMO

Nickel is the most widely used inexpensive active metal center of the heterogeneous catalysts for CO2 hydrogenation to methane. However, Ni-based catalysts suffer from severe deactivation in CO2 methanation reaction due to the irreversible sintering and coke deposition caused by the inevitable localized hotspots generated during the vigorously exothermic reaction. Herein, we demonstrate the inverse CeAlOx/Ni composite constructed on the Ni-foam structure support realizes remarkable CO2 methanation catalytic activity and stability in a wide operation temperature range from 240 to 600 °C. Significantly, CeAlOx/Ni/Ni-foam catalyst maintains its initial activity after seven drastic heating-cooling cycles from RT to 240 to 600 °C. Meanwhile, the structure catalyst also shows water resistance and long-term stability under reaction condition. The promising thermal stability and water-resistance of CeAlOx/Ni/Ni-foam originate from the excellent heat and mass transport efficiency which eliminates local hotspots and the formation of Ni-foam stabilized CeAlOx/Ni inverse composites which effectively anchored the active species and prevents carbon deposition from CH4 decomposition.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38662912

RESUMO

The conventional von Neumann architecture has proven to be inadequate in keeping up with the rapid progress in artificial intelligence. Memristors have become the favored devices for simulating synaptic behavior and enabling neuromorphic computations to address challenges. An artificial synapse utilizing the perovskite structure PbHfO3 (PHO) has been created to tackle these concerns. By employing the sol-gel technique, a ferroelectric film composed of Au/PHO/FTO was created on FTO/glass for the purpose of this endeavor. The artificial synapse is composed of Au/PHO/FTO and exhibits learning and memory characteristics that are similar to those observed in biological neurons. The recognition accuracy for both MNIST and Fashion-MNIST data sets saw an increase, reaching 92.93% and 76.75%, respectively. This enhancement resulted from employing a convolutional neural network architecture and implementing an improved stochastic adaptive algorithm. The presented findings showcase a viable approach to achieve neuromorphic computation by employing artificial synapses fabricated with PHO.

13.
J Geriatr Cardiol ; 21(3): 359-368, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38665282

RESUMO

OBJECTIVES: Misdiagnosis of acute aortic syndrome (AAS) significantly increases mortality. Tenascin-C (TN-C) is an extracellular matrix glycoprotein related to cardiovascular injury. The elevation of TN-C in AAS and whether it can discriminate sudden-onset of acute chest pain in Chinese remains unclear. METHODS: We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back pain. Measures to discriminate AAS from acute coronary syndrome (ACS) were compared and calculated. RESULTS: From October 2016 to September 2021, 376 undiagnosed patients with chest or back pain were enrolled. 166 of them were finally diagnosed as AAS, 100 were ACS and 110 without cardiovascular diseases (NCV). TN-C was significantly elevated in AAS at 18.18 ng/mL (IQR: 13.10-27.68) compared with 7.51 ng/mL (IQR: 5.67-11.38) in ACS (P < 0.001) and 3.68 ng/mL (IQR: 2.50-5.29) in NCV (P < 0.001). There was no significant difference in TN-C level among the subtypes of AAS. Of the 166 AAS patients, the peaked level of TN-C was at acute stage (P = 0.012), then a slight of decrease was observed at subacute stage. The area under receiver operating characteristic curve for AAS patients versus NCV was 0.979 (95% CI: 0.964-0.994) for TN-C. At a cutoff level of 11.474 ng/mL, TN-C has a sensitivity of 76.0%, specificity of 85.5%, accuracy of 82.0%, positive predictive value (PPV) of 76.0%, negative predictive value (NPV) of 85.5%. Diagnostic performance of TN-C was superior to D-dimer and hs-cTnT. CONCLUSIONS: The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and NCV. TN-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

14.
Plant Physiol ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669308

RESUMO

Circular RNAs (CircRNAs) play an important role in diverse biological processes; however, their origin and functions, especially in plants, remain largely unclear. Here, we used two maize (Zea mays) inbred lines, as well as 14 of their derivative RILs with different drought sensitivity, to systematically characterize 8,790 circRNAs in maize roots under well-watered (WW) and water-stress (WS) conditions. We found that a diverse set of circRNAs expressed at significantly higher levels under WS. Enhanced expression of circRNAs was associated with longer flanking introns and an enrichment of long interspersed nuclear element (LINE) retrotransposable elements. The epigenetic marks found at the back-splicing junctions of circRNA-producing genes were markedly different from canonical splicing, characterized by increased levels of H3K36me3/H3K4me1, as well as decreased levels of H3K9Ac/H3K27Ac. We found that genes expressing circRNAs are subject to relaxed selection. The significant enrichment of trait-associated sites along their genic regions suggested that genes giving rise to circRNAs were associated with plant survival rate under drought stress, implying that circRNAs play roles in plant drought responses. Furthermore, we found that overexpression of circMED16, one of the drought-responsive circRNAs, enhances drought tolerance in Arabidopsis (Arabidopsis thaliana). Our results provide a framework for understanding the intricate interplay of epigenetic modifications and how they contribute to the fine-tuning of circRNA expression under drought stress.

16.
Langmuir ; 40(17): 9289-9298, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38646870

RESUMO

Copper (Cu) emerges as a highly efficient and cheap catalytic agent for the electrochemical reduction of carbon dioxide (CO2RR), promising a sustainable route toward carbon neutrality. Despite its utility, the Cu catalyst exhibits limitations in terms of product selectivity, highlighting the need for the development of a superior catalyst design. Herein, we present a density functional theory (DFT) investigation into the selectivities of Cu-M (M = Pt, Ni, Pd, Zn, Ag, Au) bimetallic catalysts (BMCs) for the carbon dioxide reduction reaction (CO2RR). The interaction between the metals of Cu-M makes the surface electrons reconstruct so that the d-band center shifts to the Fermi level. In terms of CO2 activation, the Cu-Ni catalyst exhibits superior performance. Additionally, the Cu-Pd catalyst favors the formation of *COH along the reaction pathway, favoring the generation of CH4. Conversely, the Cu-Ni catalyst preferentially produces *CHO, thereby favoring the production of CH3OH. For the Cu-Ag catalyst, the reaction intermediates along the C2 pathway are *CO-*CHO and *COH-*CHO. The Cu-Ni catalyst follows a reaction path that proceeds via *CO-*CO → *CO-*COH → *COH-CHO. On the other hand, the Cu-Pt catalyst exhibits a reaction sequence of *CO-*CO → *CO-*CHO → *OCH-*OCH. This study provides guiding significance for the design of Cu-based bimetallic catalysts aimed at improving the selectivities and efficiency of the CO2RR process.

17.
Biomed Pharmacother ; 174: 116542, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574620

RESUMO

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14-3-3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14-3-3η-shRNA or Compound C11 (a 14-3-3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14-3-3η and protected cardiomyocytes against MIRI.


Assuntos
Proteínas 14-3-3 , Apoptose , Autofagia , Catequina , Catequina/análogos & derivados , Ferroptose , Traumatismo por Reperfusão Miocárdica , Catequina/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Proteínas 14-3-3/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Cardiotônicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ratos Sprague-Dawley
18.
Drug Des Devel Ther ; 18: 1247-1262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645988

RESUMO

Purpose: Sinomenine hydrochloride (SH) is used to treat chronic inflammatory diseases such as rheumatoid arthritis and may also be efficacious against Immunoglobulin A nephropathy (IgAN). However, no trial has investigated the molecular mechanism of SH on IgAN. Therefore, this study aims to investigate the effect and mechanism of SH on IgAN. Methods: The pathological changes and IgA and C3 depositions in the kidney of an IgAN rat model were detected by periodic acid-Schiff (PAS) and direct immunofluorescence staining. After extracting T and B cells using immunomagnetic beads, we assessed their purity, cell cycle phase, and apoptosis stage through flow cytometry. Furthermore, we quantified cell cycle-related and apoptosis-associated proteins by Western blotting. Results: SH reduced IgA and C3 depositions in stage 4 IgAN, thereby decreasing inflammatory cellular infiltration and mesangial injury in an IgAN model induced using heteroproteins. Furthermore, SH arrested the cell cycle of lymphocytes T and B from the spleen of IgAN rats. Regarding the mechanism, our results demonstrated that SH regulated the Cyclin D1 and Cyclin E1 protein levels for arresting the cell cycle and it also regulated Bax and Bcl-2 protein levels, thus increasing Cleaved caspase-3 protein levels in Jurkat T and Ramos B cells. Conclusion: SH exerts a dual regulation on the cell cycle and apoptosis of T and B cells by controlling cell cycle-related and apoptosis-associated proteins; it also reduces inflammatory cellular infiltration and mesangial proliferation. These are the major mechanisms of SH in IgAN.


Assuntos
Apoptose , Linfócitos B , Proliferação de Células , Glomerulonefrite por IGA , Morfinanos , Linfócitos T , Morfinanos/farmacologia , Morfinanos/química , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Animais , Apoptose/efeitos dos fármacos , Ratos , Proliferação de Células/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Masculino , Relação Dose-Resposta a Droga , Modelos Animais de Doenças , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Humanos , Células Cultivadas
19.
Magn Reson Imaging ; 110: 138-148, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641211

RESUMO

PURPOSE: Multi-Shot (MS) Echo-Planar Imaging (EPI) may improve the in-plane resolution of multi-b-value DWI, yet it also considerably increases the scan time. Here we explored the combination of EPI with Keyhole (EPIK) and a calibrationless reconstruction algorithm for acceleration of multi-b-value MS-DWI. METHODS: We firstly analyzed the impact of nonuniform phase accrual in EPIK on the reconstructed image. Based on insights gained from the analysis, we developed a calibrationless reconstruction algorithm based on a Space-Contrast-Coil Locally Low-Rank Tensor (SCC-LLRT) constraint for reconstruction of EPIK-acquired data. We compared the algorithm with a modified SPatial-Angular Locally Low-Rank (SPA-LLR) algorithm through simulations, phantoms, and in vivo study. We then compared EPIK with uniformly undersampled EPI for accelerating multi-b-value DWI in 6 healthy subjects. RESULTS: Through theoretical derivations, we found that the reconstruction of EPIK with a SENSE-encoding-based algorithm, such as SPA-LLR, may cause additional aliasing artifacts due to the frequency-dependent distortion of the coil sensitivity. Results from simulations, phantoms, and in vivo study verified the theoretical finding by showing that the calibrationless SCC-LLRT algorithm reduced aliasing artifacts compared with SPA-LLR. Finally, EPIK with SCC-LLRT substantially reduced the ghosting artifacts compared with uniform undersampled multi-b-value DWI, decreasing the fitting errors in ADC (0.05 ± 0.01 vs 0.10 ± 0.01, P < 0.001) and IVIM mapping (0.026 ± 0.004 vs 0.06 ± 0.006, P < 0.001). CONCLUSION: The SCC-LLRT algorithm reduced the aliasing artifacts of EPIK by using a calibrationless modeling of the multi-coil data. The dense sampling of k-space center offers EPIK a potential to improve image quality for acceleration of multi-b-value MS-DWI.


Assuntos
Algoritmos , Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas , Humanos , Imagem Ecoplanar/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Adulto , Masculino , Artefatos , Simulação por Computador , Feminino , Reprodutibilidade dos Testes , Aumento da Imagem/métodos
20.
Curr Res Food Sci ; 8: 100736, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681527

RESUMO

In this study, an in vitro co-culture model using an electric cell-substrate impedance sensing system (ECIS) for testing the impact of real-time fermentation of non-digestible carbohydrates (NDCs) by the intestinal microbiota on gut barrier function was established. We applied Lactobacillus plantarum WCFS1 as a model intestinal bacterium and alginate-pectin as immobilization polymers as well as a source of NDCs to determine the impact of pectin fermentation on the barrier function of T84 gut epithelial cells. In the first design, L. plantarum WCFS1 was encapsulated in an alginate capsule followed by embedding in an agar layer to mimic a firm mucus layer that might be present in the colon. In this experimental design, the presence of the agar layer interfered with the transepithelial electrical resistance (TEER) measurement of T84 cells. Subsequently, we removed the agar layer and used encapsulated bacteria in an alginate gel and found that the TEER measurement was adequate. The encapsulation of the L. plantarum WCFS1 does avoid direct contact with cells. Also, the encapsulation system allows higher amounts of packing densities of L. plantarum WCFS1 in a limited space which can limit the oxygen concentration within the capsule and therefore create anaerobic conditions. To test this design, T84 cells were co-incubated with L. plantarum alginate-capsules supplemented with graded loads of fermentable pectin (0, 4, and 8 mg/ml per capsule) to investigate the effect of pectin fermentation on gut barrier function. We observed that as the pectin content in the L. plantarum capsules increased, pectin showed a gradually stronger protective effect on the TEER of the gut epithelium. This could partly be explained by enhanced SCFA production as both lactate and acetate were enhanced in L. plantarum containing alginate capsules with 8 mg/ml pectin. Overall, this newly designed in vitro co-culture model allows for studying the impact of bacteria-derived fermentation products but also for studying the direct effects of NDCs on gut barrier function in a relatively high-throughput way.

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