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1.
Nat Commun ; 15(1): 3901, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724505

RESUMO

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.


Assuntos
Citoplasma , Inibidor de NF-kappaB alfa , NF-kappa B , Proteínas Tirosina Quinases , Fator de Transcrição RelA , Animais , Fosforilação , Inibidor de NF-kappaB alfa/metabolismo , Inibidor de NF-kappaB alfa/genética , Camundongos , Fator de Transcrição RelA/metabolismo , Humanos , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/genética , NF-kappa B/metabolismo , Citoplasma/metabolismo , Proteólise , Núcleo Celular/metabolismo , Replicação Viral , Células HEK293 , Transdução de Sinais , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Transporte Ativo do Núcleo Celular , Proteínas Serina-Treonina Quinases
2.
Drug Des Devel Ther ; 18: 1439-1457, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707616

RESUMO

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Glucosídeos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fenóis , Polifenóis , Estreptozocina , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Animais , Ratos , Glucosídeos/farmacologia , Glucosídeos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Fenóis/farmacologia , Fenóis/química , Ratos Sprague-Dawley
3.
Eur J Med Res ; 29(1): 261, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698427

RESUMO

BACKGROUND: Prior observational research has investigated the association between dietary patterns and Alzheimer's disease (AD) risk. Nevertheless, due to constraints in past observational studies, establishing a causal link between dietary habits and AD remains challenging. METHODS: Methodology involved the utilization of extensive cohorts sourced from publicly accessible genome-wide association study (GWAS) datasets of European descent for conducting Mendelian randomization (MR) analyses. The principal analytical technique utilized was the inverse-variance weighted (IVW) method. RESULTS: The MR analysis conducted in this study found no statistically significant causal association between 20 dietary habits and the risk of AD (All p > 0.05). These results were consistent across various MR methods employed, including MR-Egger, weighted median, simple mode, and weighted mode approaches. Moreover, there was no evidence of horizontal pleiotropy detected (All p > 0.05). CONCLUSION: In this MR analysis, our finding did not provide evidence to support the causal genetic relationships between dietary habits and AD risk.


Assuntos
Doença de Alzheimer , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doença de Alzheimer/genética , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etiologia , Humanos , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla/métodos , Fatores de Risco , Comportamento Alimentar/fisiologia , Dieta/efeitos adversos , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença
4.
Chem Biodivers ; : e202400494, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744674

RESUMO

BACKGROUND: Genus Buxus plants, commonly known as "boxwood", are widely distributed in China. The stems, branches, and leaves of the plant are traditionally used for rheumatism, toothache, chest pain, abdominal gas, and other diseases. However, an overview of the genus Buxus remains to be provided. PURPOSE: To provide a scientific basis for the appropriate use and further research the recent advancements in the traditional usage, phytochemistry, and, pharmacology of Buxus. STUDY DESIGN: Chemical composition and pharmacological correlation studies through a literature review. METHODS: Between 1970 and 2023, the available data concerning Buxus was compiled from online scientific sources, such as Sci-Finder, PubMed, CNKI, Google Scholar, and the Chinese Pharmacopoeia. Plant names were verified from "The Plant List'. Results: To date, 266 structurally diverse chemicals have been extracted and identified from the genus Buxus. Alkaloids constitute one of its primary bioactive phytochemicals. A summary of the channels of action of Cyclovirobuxine D on the cytotoxicity of a variety of cancers has been provided. CONCLUSION: Numerous findings from contemporary phytochemical and pharmacological studies support the traditional use, facilitating its application. Further research is necessary to address various shortcomings, including the identification of the active ingredients and quality control of the genus Buxus.

5.
J Nutr ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38718924

RESUMO

BACKGROUND: In lactating women, iodine metabolism is regulated and maintained by the kidneys and mammary glands. Limited research exists on how iodine absorbed by lactating women is distributed between the kidneys and breasts. OBJECTIVE: This study aimed to accurately evaluate the total iodine intake (TII), urinary iodine excretion (UIE), and breast milk iodine excretion (BMIE) in lactating women and explore the relationship between TII and total iodine excretion (TIE). METHODS: The 7-day iodine metabolism study was conducted on 41 lactating women with a mean age of 30 years in Yuncheng and Gaoqing, China, from December 2021 to August 2023. TII and TIE were calculated by measuring the iodine content in food, water, 24-h urine, feces, and breast milk. The urinary iodine excretion rate (UIER), breast milk iodine excretion rate (BMIER), and partitioning of iodine excretion between urine and breast milk were determined. RESULTS: Iodine metabolism studies were performed for 285 days. The median TII and TIE values were 255 and 263 µg/d, respectively. With an increase in TII, UIER, and BMIER, the UIE and BMIE to TII ratio exhibited a downward trend. The median UIER, BMIER, and proportion of iodine excreted in urine and breast milk were 51.5%, 38.5%, 52%, and 37%, respectively. When the TII was <120 µg/d, the BMIER decreased with the increase of the TII (ß, -0.90, 95% CI: -1.08, -0.72). CONCLUSIONS: When maternal iodine intake is low, the proportion in breast milk increases, ensuring sufficient iodine nutrition for infants. In addition, the UIE of lactating women with adequate iodine levels was higher than their BMIE.

6.
Front Neurosci ; 18: 1366294, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721049

RESUMO

Introduction: Transformer network is widely emphasized and studied relying on its excellent performance. The self-attention mechanism finds a good solution for feature coding among multiple channels of electroencephalography (EEG) signals. However, using the self-attention mechanism to construct models on EEG data suffers from the problem of the large amount of data required and the complexity of the algorithm. Methods: We propose a Transformer neural network combined with the addition of Mixture of Experts (MoE) layer and ProbSparse Self-attention mechanism for decoding the time-frequency-spatial domain features from motor imagery (MI) EEG of spinal cord injury patients. The model is named as EEG MoE-Prob-Transformer (EMPT). The common spatial pattern and the modified s-transform method are employed for achieving the time-frequency-spatial features, which are used as feature embeddings to input the improved transformer neural network for feature reconstruction, and then rely on the expert model in the MoE layer for sparsity mapping, and finally output the results through the fully connected layer. Results: EMPT achieves an accuracy of 95.24% on the MI EEG dataset for patients with spinal cord injury. EMPT has also achieved excellent results in comparative experiments with other state-of-the-art methods. Discussion: The MoE layer and ProbSparse Self-attention inside the EMPT are subjected to visualisation experiments. The experiments prove that sparsity can be introduced to the Transformer neural network by introducing MoE and kullback-leibler divergence attention pooling mechanism, thereby enhancing its applicability on EEG datasets. A novel deep learning approach is presented for decoding EEG data based on MI.

7.
Plant Cell ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38735686

RESUMO

Increasing grain yield is a major goal of breeders due to the rising global demand for food. We previously reported that the miR397-LACCASE (OsLAC) module regulates brassinosteroid (BR) signaling and grain yield in rice (Oryza sativa). However, the precise roles of laccase enzymes in the BR pathway remain unclear. Here, we report that OsLAC controls grain yield by preventing the turnover of TRANSTHYRETIN-LIKE (OsTTL), a negative regulator of BR signaling. Overexpressing OsTTL decreased BR sensitivity in rice, while loss-of-function of OsTTL led to enhanced BR signaling and increased grain yield. OsLAC directly binds to OsTTL and regulates its phosphorylation-mediated turnover. The phosphorylation site Ser226 of OsTTL is essential for its ubiquitination and degradation. Overexpressing the dephosphorylation-mimic form of OsTTL (OsTTLS226A) resulted in more severe defects than did overexpressing OsTTL. These findings provide insight into the role of an ancient laccase in BR signaling and suggest that the OsLAC-OsTTL module could serve as a target for improving grain yield.

8.
Anal Bioanal Chem ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739158

RESUMO

Nanozymes are nanomaterials with mimetic enzyme properties and the related research has attracted much attention. It is of great value to develop methods to construct nanozymes and to study their application in bioanalysis. Herein, the metal-ligand cross-linking strategy was developed to fabricate superstructure nanozymes. This strategy takes advantage of being easy to operate, adjustable, cheap, and universal. The fabricated superstructure nanozymes possess efficient peroxidase-like catalytic activity. The enzyme reaction kinetic tests demonstrated that for TMB and H2O2, the Km is 0.229 and 1.308 mM, respectively. Furthermore, these superstructure nanozymes are applied to highly efficient and sensitive detection of glucose. The linear range for detecting glucose is 20-2000 µM, and the limit of detection is 17.5 µM. Furthermore, mechanistic research illustrated that this integrated system oxidizes glucose to produce hydrogen peroxide and further catalyzes the production of ·OH and O2·-, which results in a chromogenic reaction of oxidized TMB for the detection of glucose. This work could not only contribute to the development of efficient nanozymes but also inspire research in the highly sensitive detection of other biomarkers.

9.
Arch Insect Biochem Physiol ; 115(4): e22114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38659314

RESUMO

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene.


Assuntos
Blattellidae , Proteínas de Insetos , Oviposição , Pigmentação , Interferência de RNA , Animais , Blattellidae/genética , Blattellidae/fisiologia , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Masculino , Pigmentação/genética , Corte , Melaninas/metabolismo , Comportamento Sexual Animal
10.
Int J Biol Sci ; 20(6): 2219-2235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617542

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Metabolismo dos Lipídeos/genética , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Receptores de Quimiocinas , Inflamação
11.
ACS Omega ; 9(14): 15818-15832, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617642

RESUMO

How to realize efficient treatment of coal slime generated by a coal washing operation is an urgent problem to be solved in this industry. The presence of clay minerals, especially highly hydrophilic montmorillonite (MMT), is the key to the poor treatment effect of coal slime. Polyacrylamide (PAM) is very popular as a polymer agent to improve the treatment of coal slime. However, when it is used to treat coal slime with a high content of MMT, the selection of PAM type and the mechanism of action are still lacking. In this study, the effects of different types of PAM on the treatment of coal slime water containing MMT are considered by sedimentation and press filtration tests. The interaction mechanism of PAM on the MMT surface is studied by using ζ-potential, Brunauer-Emmett-Teller (BET) analysis, low-field nuclear magnetic resonance, density functional theory (DFT), and molecular dynamics (MD) simulations. The results show that the three PAM can improve the sedimentation and filtration effect of coal slime water, and the performance is CPAM > NPAM > APAM. The ζ-potential of the MMT (001) surface increases under the action of three PAM, and the effect of CPAM is the most significant. The adsorption of PAM on the MMT (001) surface has the ability to neutralize the surface charge of MMT. The flocculation of MMT particles under PAM results in an increase of particle size and a decrease of specific surface area. Meanwhile, the pore volume of MMT decreases, and the average pore size increases. In addition, PAM mainly removes vicinal water on the MMT surface. The active sites of the MMT surface and PAM are calculated by DFT. The adsorption of three PAM structural units on the MMT Na-001 surface and non-001 surface is nonbonding interaction, and the adsorption energy of CPAM is the largest. And the left shift of εp of the O atom on the MMT surface is conducive to the stable adsorption of CPAM. The MD results show that the concentration of water molecules on the surface of MMT Na-001 decreases after PAM is adsorbed on the MMT Na-001 surface, indicating that PAM can keep water molecules away from the surface of MMT, which means that the hydrophobicity of the MMT surface is enhanced. This study has guiding significance for the selection of PAM and the development of new flocculants in the treatment of coal slime with a high content of MMT.

12.
BMC Cancer ; 24(1): 474, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622609

RESUMO

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.


Assuntos
Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos C57BL , Linfócitos T CD8-Positivos , Quimiocinas , Carcinoma Pulmonar de Lewis/terapia , Carcinoma Pulmonar de Lewis/patologia , Microambiente Tumoral , Linhagem Celular Tumoral
13.
J Adv Res ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38609050

RESUMO

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

14.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1157-1169, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38658155

RESUMO

Cytokinin response factors (CRFs), as unique transcription factors in plants, play crucial roles in regulating development, phytohormone signaling pathway, and stress responses. In this study, we identified nine CRF genes from the rice genome by conducting a BLAST analysis using the protein sequences of twelve Arabidopsis AtCRFs. These genes are located on seven different rice chromosomes. We conducted a comprehensive analysis of the conserved domains, physicochemical properties, secondary structures, and phylogenetic relationships of rice CRF proteins using various online tools and local software. Additionally, we analyzed the exon-intron structures and cis-acting elements of OsCRFs, and found an abundance of elements relevant to phytohormone response and stress response on the promoters of rice CRF genes. Spatial-temporal expression pattern analysis revealed that four of the OsCRFs were barely expressed in all tested samples, while the other five were highly expressed in the leaf, panicle, or seed of rice. Microarray data showed that OsCRF genes are regulated to varying degrees by abscisic acid, auxin, cytokinin, and jasmonic acid. Furthermore, through analyzing the RNA-seq data, we found that OsCRFs are primarily involved in plant response to temperature stress (chilling and heat), with several OsCRFs also implicated in drought response, while hardly any respond to salt stress. This study provides an important basis for the functional characterization of rice CRF family genes.


Assuntos
Citocininas , Regulação da Expressão Gênica de Plantas , Oryza , Filogenia , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Citocininas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Família Multigênica , Estresse Fisiológico/genética , Perfilação da Expressão Gênica , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo
15.
Res Sq ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38562764

RESUMO

Background: Polycyclic aromatic hydrocarbons (PAHs) have been linked to adverse birth outcomes, but few epidemiological studies to date have evaluated associations between urinary PAH metabolites and oxidative stress biomarkers in pregnancy. Methods: We measured a total of 7 PAH metabolites and 2 oxidative stress biomarkers (malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG)) in urine samples collected up to three times during pregnancy in 159 women enrolled at antenatal clinics at the University of California Los Angeles during 2016-2019. Using multiple linear regression models, we estimated the percentage change (%) and 95% confidence interval (CI) in 8-OHdG and MDA measured at each sample collection time per doubling of PAH metabolite concentrations. Results: Most PAH metabolites were positively associated with both urinary oxidative stress biomarkers, MDA and 8-OHdG, with stronger associations in early and late pregnancy. Women pregnant with male fetuses exhibited slightly larger increases in both MDA and 8-OHdG in association with PAH exposures in early and late pregnancy. Conclusion: Urinary OH-PAH biomarkers are associated with increases in oxidative stress during pregnancy, especially in early and late pregnancy. Sex differences in associations between PAH exposures and oxidative stress need to be further explored in the future.

16.
Clin Neurol Neurosurg ; 241: 108285, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38636361

RESUMO

BACKGROUND: Stroke-induced heart syndrome is a feared complication of ischemic stroke, that is commonly encountered and has a strong association with unfavorable prognosis. More research is needed to explore underlying mechanisms and inform clinical decision making. This study aims to explore the relationship between the early systemic immune-inflammation (SII) index and the cardiac complications after acute ischemic stroke. METHODS: Consecutive patients with acute ischemic stroke were prospectively collected from January 2020 to August 2022 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections or cancer on admission. SII index [(neutrophils × platelets/ lymphocytes)/1000] was calculated from laboratory data at admission. RESULTS: A total of 121 patients were included in our study, of which 24 (19.8 %) developed cardiac complications within 14 days following acute ischemic stroke. The SII level was found higher in patients with stroke-heart syndrome (p<.001), which was an independent predictor of stroke-heart syndrome (adjusted odds ratio 5.089, p=.002). CONCLUSION: New-onset cardiovascular complications diagnosed following a stroke are very common and are associated with early SII index.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38639703

RESUMO

INTRODUCTION: This study aimed to evaluate the effects of varying auxiliaries on tooth movement and stress distribution when maxillary central incisors were torqued 1° with a clear aligner through finite element analysis. METHODS: Three-dimensional finite element models, including maxillary alveolar bone, periodontal ligament, dentition, and clear aligner, were constructed. According to the auxiliaries designed on the maxillary central incisor, 5 models were created: (1) without auxiliaries (control model), (2) with the power ridge, (3) with the semi-ellipsoid attachment, (4) with the horizontal rectangular attachment, and (5) with the horizontal cylinder attachment. The tooth movement and periodontal ligament stress distribution after a palatal root torque of 1° were analyzed for each of the 5 models. RESULTS: With 1° torque predicted, the maxillary central incisor without auxiliaries showed a tendency of labial tipping, mesial tipping, and intrusion. The rotation center moved occlusally in the power ridge model. The labiolingual inclination variation increased in the semi-ellipsoid attachment model but decreased in the power ridge model. The maxillary central incisor is twisted in the distal direction in the power ridge model. The maxillary central incisor of the horizontal rectangular attachment and the horizontal cylinder attachment model behaved similarly to the control model. Periodontal stresses were concentrated in the cervical and apical areas. The maximum von Mises stresses were 11.6, 12.4, 3.81, 1.14, and 11.0 kPa in the 5 models. The semi-ellipsoid attachment model exhibited a more uniform stress distribution than the other models. CONCLUSIONS: Semi-ellipsoid attachment performed better efficacy on labiolingual inclination, and power ridge performed better efficacy on root control. However, a distal twist of maxillary incisors could be generated by the power ridge.

18.
Inorg Chem ; 63(15): 6787-6797, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38556762

RESUMO

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

19.
Psychiatry Res ; 335: 115886, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574699

RESUMO

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.


Assuntos
Alucinógenos , Transtornos Mentais , N-Metil-3,4-Metilenodioxianfetamina , Transtorno Obsessivo-Compulsivo , Humanos , Alucinógenos/efeitos adversos , Psilocibina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , Dietilamida do Ácido Lisérgico/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/induzido quimicamente , Transtorno Obsessivo-Compulsivo/tratamento farmacológico
20.
Am J Cancer Res ; 14(3): 1402-1418, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590397

RESUMO

The role of vesicular genes in the development of colorectal cancer (CRC) is crucial. Analyzing alterations in these genes at multi-omics can aid in understanding the molecular pathways behind colorectal carcinogenesis and identifying potential treatment targets. However, studies on the overall alteration of vesicular genes in CRC are still lacking. In this study, we aimed to investigate the relationship between vesicle genetic alterations and CRC progression. To achieve this, we analyzed molecular alterations in CRC vesicle genes at eight levels, including mRNA, protein, and epigenetic levels. Additionally, we examined CRC overall survival-related genes that were obtained from a public database. Our analysis of chromatin structural variants, DNA methylation, chromatin accessibility, and proteins (including phosphorylation, ubiquitination, and malonylation), along with RNA-seq data from the TCGA database, revealed multiple levels of alterations in CRC vesicle genes in the collected tissue samples. We progressively examined the alterations of vesicle genes in mRNA and protein levels in CRC and discovered the hub genes. Further investigation identified the probable essential transcription factors. This study contributes to a thorough knowledge of the connection between vesicle gene alterations at multiple levels and the development of CRC and offers a theoretical framework for the identification of novel treatment targets.

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