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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 662-670, 2024 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-38948267

RESUMO

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Modelos Logísticos , Feminino , Masculino , China/epidemiologia , Estudos de Coortes , Saúde Pública , Incidência
2.
Pest Manag Sci ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943354

RESUMO

BACKGROUND: Root-knot nematodes (RKNs), Meloidogyne spp., are one of the most destructive polyphagous plant-parasitic nematodes. They pose a serious threat to global food security and are difficult to control. Entomopathogenic nematodes (EPNs) show promise in controlling RKNs. However, it remains unclear whether the volatile organic compounds (VOCs) emitted from EPN-infected cadavers can control RKNs. RESULTS: We investigated the fumigation activity of VOCs released from cadavers infected by five different species of EPNs on RKNs in Petri dishes, and found that VOCs released from Steinernema feltiae (SN strain) and S. carpocapsae (All strain) infected cadavers had a significant lethal effect on second-stage juveniles (J2s) of Meloidogyne incognita. The VOCs released from the cadavers infected with S. feltiae were analyzed using SPME-GC/MS. Dimethyl disulfide (DMDS), tetradecane, pentadecane, and butylated hydroxytoluene (BHT), were selected for a validation experiment with pure compounds. The DMDS compound had significant nematicidal activity and repelled J2s. DMDS also inhibited egg hatching and the invasion of tomato roots by J2s. In a pot experiment, the addition of S. feltiae-infected cadavers and cadavers wrapped with a 400-mesh nylon net also significantly reduced the population of RKNs in tomato roots after 7 days. The number of root knots and eggs was reduced by 58% and 74.34%, respectively, compared to the control. CONCLUSION: These results suggested that the VOCs emitted by the EPN-infected cadavers affected various developmental stages of M. incognita and thus have the potential to be used in controlling RKNs through multiple methods. © 2024 Society of Chemical Industry.

3.
Talanta ; 278: 126452, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38943766

RESUMO

Septic cardiomyopathy (SCM) is the main cause of death in critically ill patients with sepsis. However, its definitive pathogenic mechanisms remain to be elucidated. Lipid droplets (LDs) are important sub-organelles that store lipids and participate in intracellular lipid metabolism. Abnormal aggregation and altered polarity of LDs are associated with the development of several cardiac diseases. To date, visualization of abnormal polarity in models of SCM has not been achieved. Herein, we designed and synthesized the probe BDP-551, a polarity-sensitive probe possessing a donor-π-acceptor (D-π-A) structure. BDP-551 exhibits excellent photostability, high LDs targeting, near-infrared (NIR) emission (up to 678 nm) and strong polarity sensitivity. With the help of confocal imaging microscopy, the BDP-551 was able to detect the polarity changes induced in the SCM model cells and visualize the yolk sac region in hypoxic as well as inflamed living zebrafish. In addition, the BDP-551 has been successfully applied to visualize the polarity changes of mice hearts with SCM, proving a decrease of microenvironmental polarity in the development of SCM. Therefore, BDP-551 in this study can be used as a reliable tool to investigate polarity fluctuations and provide new insights into the associated pathogenic and therapeutic mechanisms on SCM.

4.
Foods ; 13(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38890942

RESUMO

Polycyclic aromatic hydrocarbons are considered to be potentially genotoxic and carcinogenic to humans. For non-smoking populations, food is the main source of polycyclic aromatic hydrocarbons exposure. Due to their lipophilic nature, oils and fats rank among the food items with the highest polycyclic aromatic hydrocarbon content. Consequently, the detection of polycyclic aromatic hydrocarbons in edible oils is critical for the promotion of human health. This paper reviews sample pretreatment methods, such as liquid-phase-based extraction methods, adsorbent-based extraction methods, and the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, combined with detection techniques like mass spectrometry and chromatography-based techniques for accurate quantification of polycyclic aromatic hydrocarbons in edible oils since 2010. An overview on the advances of the methods discussed herein, along with a commentary addition of current challenges and prospects, will guide researchers to focus on developing more effective detection methods and control measures to reduce the potential risks and hazards posed by polycyclic aromatic hydrocarbons.

5.
Nat Commun ; 15(1): 4535, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806516

RESUMO

Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 Å using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.


Assuntos
Microscopia Crioeletrônica , Criptófitas , Complexo de Proteína do Fotossistema II , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/química , Criptófitas/metabolismo , Clorofila/metabolismo , Proteínas de Ligação à Clorofila/metabolismo , Proteínas de Ligação à Clorofila/química , Multimerização Proteica , Clorofila A/metabolismo , Clorofila A/química , Modelos Moleculares , Complexos de Proteínas Captadores de Luz/metabolismo , Complexos de Proteínas Captadores de Luz/química
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124351, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38692109

RESUMO

Epidermal growth factor receptor (EGFR) plays a pivotal role in the initiation and progression of gliomas. In particular, in glioblastoma, EGFR amplification emerges as a catalyst for invasion, proliferation, and resistance to radiotherapy and chemotherapy. Current approaches are not capable of providing rapid diagnostic results of molecular pathology. In this study, we propose a terahertz spectroscopic approach for predicting the EGFR amplification status of gliomas for the first time. A machine learning model was constructed using the terahertz response of the measured glioma tissues, including the absorption coefficient, refractive index, and dielectric loss tangent. The novelty of our model is the integration of three classical base classifiers, i.e., support vector machine, random forest, and extreme gradient boosting. The ensemble learning method combines the advantages of various base classifiers, this model has more generalization ability. The effectiveness of the proposed method was validated by applying an individual test set. The optimal performance of the integrated algorithm was verified with an area under the curve (AUC) maximum of 85.8 %. This signifies a significant stride toward more effective and rapid diagnostic tools for guiding postoperative therapy in gliomas.


Assuntos
Receptores ErbB , Glioma , Espectroscopia Terahertz , Humanos , Glioma/genética , Glioma/patologia , Glioma/diagnóstico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Espectroscopia Terahertz/métodos , Aprendizado de Máquina , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Amplificação de Genes , Algoritmos , Máquina de Vetores de Suporte
7.
Artigo em Inglês | MEDLINE | ID: mdl-38676497

RESUMO

BACKGROUND: Atherosclerosis (AS) is the leading cause of mortality in elderly individuals worldwide. Anmeidan (AMD) is a Traditional Chinese Medicine (TCM) formula composed of many herbs, many of which have been accepted for treating AS. This study aimed to explore whether AMD can inhibit the progress of AS and its possible mechanism. METHODS: ApoE-/- mice were used to establish the AS model and evaluate the therapeutic effect of AMD on AS. Based on network pharmacology technology, the potential mechanism of AMD for treating AS was explored, and lipid metabolism pathways related to AS were mainly studied. Next, the effects of AMD on liver lipid levels, antioxidant capacity, liver tissue morphology, and gene expression related to lipid metabolism in ApoE-/- mice were investigated. Cellular experiments were performed to confirm the lipid-lowering effect of AMD. Finally, the AMD composition was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: In ApoE-/- mice, AMD effectively alleviated AS by reducing serum total cholesterol, triglyceride, low-density lipoprotein levels, and plaque area, and increasing high-density lipoprotein levels. Network pharmacology indicated that AMD may suppress AS by regulating lipid metabolism pathways with multiple TCM components, which is consistent with the results of in vivo experiments and LC-MS/MS component identification. AMD significantly reduced liver lipid aggregation, intensified antioxidant enzyme activity, and upregulated the mRNA levels of ABCA1, ABCG1, and LDLR with increased cholesterol efflux. In addition, AMD decreased cholesterol levels in foam cells. CONCLUSIONS: This study confirmed that AMD could treat AS by regulating lipid metabolism and preliminarily explored the related mechanism. These findings provide new ideas for the treatment of AS with TCM.

8.
Front Plant Sci ; 15: 1381040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576791

RESUMO

In our earlier works, we have shown that the rate-limiting steps, associated with the dark-to-light transition of Photosystem II (PSII), reflecting the photochemical activity and structural dynamics of the reaction center complex, depend largely on the lipidic environment of the protein matrix. Using chlorophyll-a fluorescence transients (ChlF) elicited by single-turnover saturating flashes, it was shown that the half-waiting time (Δτ 1/2) between consecutive excitations, at which 50% of the fluorescence increment was reached, was considerably larger in isolated PSII complexes of Thermostichus (T.) vulcanus than in the native thylakoid membrane (TM). Further, it was shown that the addition of a TM lipid extract shortened Δτ 1/2 of isolated PSII, indicating that at least a fraction of the 'missing' lipid molecules, replaced by detergent molecules, caused the elongation of Δτ 1/2. Here, we performed systematic experiments to obtain information on the nature of TM lipids that are capable of decreasing Δτ 1/2. Our data show that while all lipid species shorten Δτ 1/2, the negatively charged lipid phosphatidylglycerol appears to be the most efficient species - suggesting its prominent role in determining the structural dynamics of PSII reaction center.

9.
Sci Rep ; 14(1): 7253, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538666

RESUMO

Due to the highly conserved structure, animal mitochondrial genome (mtDNA) is widely used in classification, evolution, phylogeny, population genetic structure and other fields. We reported on the five circle multipartite mtDNAs of a newly described species of Globodera, Globodera vulgaris (Gv) from potatoes in China. The results showed that the mtDNA of Gv was obtained through second- and third-generation sequencing, with a total length of 42,995 bp. It contained 12 protein-coding genes, two rRNA genes and 17 tRNA genes, which were distributed in different subgenomic circles. Comparison of the differences in mtDNA among Gv, G. rostochiensis, G. pallida and G. ellingtonae showed that the size and arrangement of the genes in the mtDNA of the genus Globodera were variable and not conserved. The codon usage bias of the mitochondrial protein-coding gene of Gv showed that Gv might have originated from locally and more primitive group of existing Globodera. Based on the cytochrome c oxidase subunits I genes (COX1) and the nicotinamide adenine dinucleotide dehydrogenase subunits I genes (ND1), and the results showed that Gv was clustered with Globodera spp. according to the COX1 and ND1 in scmtDNA-V, while Gv was clustered with Meloidogyne spp. according to ND1 in scmtDNA-III. The results of this study provided a new basis for understanding the multipartite structure of mtDNA as a phylogenetic and taxonomic feature of the genus Globodera. The number of subgenomic circles is a diagnostic feature of species and the arrangement order and size of mitochondrial protein-coding genes also have important application value in species identification within the genus.


Assuntos
Genoma Mitocondrial , Tylenchoidea , Animais , Genoma Mitocondrial/genética , Filogenia , Tylenchoidea/genética , DNA Mitocondrial/genética , Proteínas Mitocondriais/genética
10.
Environ Geochem Health ; 46(4): 116, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478189

RESUMO

Ecological pollution caused by heavy metals released from sediments is a worldwide concern. However, the effect of changes in sediment speciation on their release of heavy metals has not been adequately reported. In this study, the research focused on Pb and Cr in the ice period of Wuliangsuhai. This study analyzed changes in the sediment speciation of Pb and Cr before and after a release experiment using four risk assessment methods while varying the temperature, pH, and salinity of the water column. The results indicated that the total concentration of Pb ranged from 11.17 to 24.25 mg/kg, while for Cr it ranged from 42.26 to 69.68 mg/kg. Both elements exhibited mild contamination. The release of Pb and Cr from sediments increases with increasing water temperature, mainly due to the conversion of the residual fraction of Pb to the Fe-Mn oxide fraction and Cr converting more residual fraction to the organic matter and sulfide fraction. The release of sediment Pb and Cr decreased with increasing pH, with Pb converting more acid extractable fraction to the residual fraction and Cr converting more organic matter and sulfide fraction to the residual fraction. In contrast, the release of Pb and Cr increased and then decreased with increasing salinity. For Pb, the acid extractable fraction was more susceptible to conversion to the residual fraction by environmental influences, whereas for Cr, the organic matter and sulfide fraction were susceptible to conversion to the residual fraction.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Lagos , Gelo , Chumbo , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Água , Medição de Risco , Sulfetos , China
11.
Sci Total Environ ; 919: 170849, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38350570

RESUMO

BACKGROUND: Emerging evidence suggests that exposure to outdoor artificial light at night (ALAN) may be associated with diabetes. However, limited research explores the relationship between outdoor ALAN and gestational diabetes mellitus (GDM). METHODS: We utilized data from a multilevel infant and early life cohort study conducted in Sichuan Province, China, between February 2018 and April 2021. A total of 9,120 participants were included in the final analysis. Outdoor ALAN exposure at participants' residential locations was estimated using time-varying satellite data, focusing on persistent night-time illumination at a scale of approximately 500x500m. The information about GDM was obtained from medical records. After adjusting for potential confounders, multivariable logistic regression models and restricted cubic splines were employed to estimate the association between ALAN exposure during pregnancy and GDM. RESULTS: Among the total recruitments, 1,484 (16.27%) women were diagnosed with GDM. Compared to women without GDM, those with GDM had a significantly higher mean outdoor ALAN exposure during pregnancy (18.98 nW/cm2/sr1 vs 24.28 nW/cm2/sr1, P < 0.001). Results from multivariable logistic models showed that higher outdoor ALAN exposure during pregnancy could increase the risk of GDM (OR (95% CI) 1st+2nd trimesters ALAN = 1.253 (1.157-1.356)). Meanwhile, results from the restricted cubic spline further indicated a non-linear association between outdoor ALAN exposure during pregnancy and GDM. Generally, with the radiance of the first two trimesters of ALAN increasing to about 17.9 nW/cm2/sr1, outdoor ALAN exposure became a risk factor for GDM. However, when the radiance of ALAN reached about 40.7 nW/cm2/sr1, the continued increasing OR estimation (OR (95% CI) = 1.489 (1.223-1.814)) of outdoor ALAN changed to steady. CONCLUSION: Our findings suggested that high levels of outdoor ALAN exposure during pregnancy can be associated with an increased risk of GDM, and a non-linear relationship pattern might exist. These findings substantially augment existing evidence, positing outdoor ALAN as an emergent, modifiable risk factor for GDM.


Assuntos
Diabetes Gestacional , Gravidez , Humanos , Feminino , Masculino , Diabetes Gestacional/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Poluição Luminosa , China/epidemiologia
12.
Eur J Pharmacol ; 968: 176354, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316248

RESUMO

Sepsis is a life-threatening condition involving dysfunctional organ responses stemming from dysregulated host immune reactions to various infections. The lungs are most prone to failure during sepsis, resulting in acute lung injury (ALI). ALI is associated with oxidative stress and inflammation, and current therapeutic strategies are limited. To develop a more specific treatment, this study aimed to synthesise Prussian blue nanozyme (PBzyme), which can reduce oxidative stress and inflammation, to alleviate ALI. PBzyme with good biosafety was synthesised using a modified hydrothermal method. PBzyme was revealed to be an activator of haem oxygenase-1 (HO-1), improving survival rate and ameliorating lung injury in mice. Zinc protoporphyrin, an inhibitor of HO-1, inhibited the prophylactic therapeutic efficacy of PBzyme on ALI, and affected the nuclear factor-κB signaling pathway and activity of HO-1. This study demonstrates that PBzyme can alleviate oxidative stress and inflammation through HO-1 and has a prophylactic therapeutic effect on ALI. This provides a new strategy and direction for the clinical treatment of sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Ferrocianetos , Sepse , Camundongos , Animais , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Heme Oxigenase-1/metabolismo , Pulmão , Inflamação/complicações , Inflamação/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo
13.
Front Microbiol ; 15: 1319895, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343715

RESUMO

In recent years, the problems associated with continuous cropping (CC) that cause soil degradation have become increasingly serious. As a key soil quality property, dissolved organic matter (DOM) affects the circulation of carbon and nutrients and the composition of bacterial communities in soil. However, research on the changes in the molecular composition of DOM after CC is limited. In this study, the soil chemical properties, DOM chemical diversity, bacterial community structure, and their interactions are explored in the soil samples from different CC years (CC1Y, CC3Y, CC5Y, and CC7Y) of tobacco. With increasing CC year of tobacco, most of the soil chemical properties, such as total carbon, total nitrogen and organic matter, decreased significantly, while dissolved organic carbon first decreased and then increased. Likewise, the trends of DOM composition differed with changing duration of CC, such as the tannin compounds decreased from 18.13 to 13.95%, aliphatic/proteins increased from 2.73 to 8.85%. After 7 years of CC, the soil preferentially produced compounds with either high H/C ratios (H/C > 1.5), including carbohydrates, lipids, and aliphatic/proteins, or low O/C ratios (O/C < 0.1), such as unsaturated hydrocarbons. Furthermore, core microorganisms, including Nocardioides, wb1-P19, Aquabacterium, Methylobacter, and Thiobacillus, were identified. Network analysis further indicated that in response to CC, Methylobacter and Thiobacillus were correlated with the microbial degradation and transformation of DOM. These findings will improve our understanding of the interactions between microbial community and DOM in continuous cropping soil.

14.
J Cell Mol Med ; 28(3): e18099, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38164021

RESUMO

Our previous study found that miR-26a alleviates aldosterone-induced tubulointerstitial fibrosis (TIF). However, the effect of miR-26a on TIF in diabetic kidney disease (DKD) remains unclear. This study clarifies the role and possible mechanism of exogenous miR-26a in controlling the progression of TIF in DKD models. Firstly, we showed that miR-26a was markedly decreased in type 2 diabetic db/db mice and mouse tubular epithelial cells (mTECs) treated with high glucose (HG, 30 mM) using RT-qPCR. We then used adeno-associated virus carrying miR-26a and adenovirus miR-26a to enhance the expression of miR-26a in vivo and in vitro. Overexpressing miR-26a alleviated the TIF in db/db mice and the extracellular matrix (ECM) deposition in HG-stimulated mTECs. These protective effects were caused by reducing expression of protease-activated receptor 4 (PAR4), which involved in multiple pro-fibrotic pathways. The rescue of PAR4 expression reversed the anti-fibrosis activity of miR-26a. We conclude that miR-26a alleviates TIF in DKD models by directly targeting PAR4, which may provide a novel molecular strategy for DKD therapy.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , Animais , Camundongos , Nefropatias Diabéticas/metabolismo , Fibrose , MicroRNAs/metabolismo , Receptores de Trombina
15.
J Adv Res ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38219870

RESUMO

INTRODUCTION: Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention in OA and related drug development due to their unique RNA sequence characteristics.Therefore,exploring the role of cirRNAs in the occurrence and development of OA is of paramount importance for the development of effective medications for OA. OBJECTIVES: To identify a novel circRNA, circUbqln1, for treating osteoarthritis and elucidate its pathophysiological role and mechanisms in the treatment of OA. METHODS: The circUbqln1 expression and distribution were determined by qRT-PCR and FISH. XBP1 gene knockout(XBP1 cKO) spontaneous OA and DMM model and WT mouse CIOA model were used to explore the role of XBP1 and circUbqln1 in OA.Overexpression or knockdown of circUbqln1 lentivirus was used to observe the impacts of circUbqln1 on primary chondrocytes,C28/I2 and mice in vitro and in vivo.Chromatin immunoprecipitation,luciferase reporter assay,RNA pulldown,mass spectrometry,RNA immunoprecipitation,fluorescence in situ hybridization,and flow cytometry to explore the molecular mechanisms of circUbqln1. RESULTS: It was found that cartilage-specific XBP1 cKO mice exhibited a faster OA progression compared to normal's.Importantly,transcript factor XBP1s has the capacity to impede the biogenesis of circUbqln1,derived from Ubqln1. The circUbqln1 promotes cartilage catabolism and inhibits anabolism, therefore accelerates the occurrence of OA.Mechanismly,circUbqln1 can translocate to the chondrocyte nucleus with the assistance of phosphorylated 14-3-3ζ, upregulate the transcriptional activity of the proline dehydrogenase(Prodh) promoter and PRODH enzyme activity. Consequently, this leads to the promotion of proline degradation and the inhibition of collagen synthesis,ultimately culminating in the impairment of cartilage and its structural integrity. CONCLUSION: CircUbqln1 plays a crucial role in the occurrence and development of OA, indicating that the inhibition of circUbqln1 holds promise as a significant approach for treating OA in the future.

16.
Sci Rep ; 14(1): 2067, 2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267496

RESUMO

Novel biologics in MG therapy research is on the rise. This research aimed to investigate the characteristics of registered trials on novel therapies for myasthenia gravis on ClinicalTrials.gov. This cross-sectional study used a descriptive approach to assess the features of the included trials on ClinicalTrials.gov. We found 62 registered trials from 2007 to 2023 on ClinicalTrials.gov. The results showed a yearly rise in the number of registered trials (r = 0.76, p < 0.001). Following 2017, more industry-sponsored trials were conducted (91.5% [43] vs. 60% [9], p = 0.009), fewer results were released (10.6% [5] vs. 60% [9], p = 0.001), and more trials entered phase 3 (67.4% [31] vs. 20% [2], p = 0.001). The most researched novel medications were neonatal Fc receptor inhibitors (51.2% [21]), complement inhibitors (39.0% [16]), and B cell depletors (14.6% [6]). According to the website's data, the neonatal Fc receptor inhibitors and complement inhibitors were effective in treating myasthenia gravis patients in three trials (NCT03315130, NCT03669588, and NCT00727194). This study provides valuable insights into the profile of registered trials on novel therapies for myasthenia gravis. More clinical studies are needed in the future to prove the value of its application.


Assuntos
Produtos Biológicos , Miastenia Gravis , Recém-Nascido , Humanos , Estudos Transversais , Linfócitos B , Inativadores do Complemento , Miastenia Gravis/tratamento farmacológico
17.
J Invertebr Pathol ; 203: 108067, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278342

RESUMO

Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs.


Assuntos
Monoterpenos Cicloexânicos , Insetos , Rabditídios , Animais , Rabditídios/fisiologia
18.
Acta Pharmacol Sin ; 45(5): 1032-1043, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38286833

RESUMO

It is well established that the synthesis of extracellular matrix (ECM) in mesangial cells is a major determinant of diabetic kidney disease (DKD). Elucidating the major players in ECM synthesis may be helpful to provide promising candidates for protecting against DKD progression. tRF3-IleAAT is a tRNA-derived fragment (tRF) produced by nucleases at tRNA-specific sites, which is differentially expressed in the sera of patients with diabetes mellitus and DKD. In this study we investigated the potential roles of tRFs in DKD. Db/db mice at 12 weeks were adapted as a DKD model. The mice displayed marked renal dysfunction accompanied by significantly reduced expression of tRF3-IleAAT and increased ferroptosis and ECM synthesis in the kidney tissues. The reduced expression of tRF3-IleAAT was also observed in high glucose-treated mouse glomerular mesangial cells. We administered ferrostatin-1 (1 mg/kg, once every two days, i.p.) to the mice from the age of 12 weeks for 8 weeks, and found that inhibition of the onset of ferroptosis significantly improved renal function, attenuated renal fibrosis and reduced collagen deposition. Overexpression of tRF3-IleAAT by a single injection of AAV carrying tRF3-IleAAT via caudal vein significantly inhibited ferroptosis and ECM synthesis in DKD model mice. Furthermore, we found that the expression of zinc finger protein 281 (ZNF281), a downstream target gene of tRF3-IleAAT, was significantly elevated in DKD models but negatively regulated by tRF3-IleAAT. In high glucose-treated mesangial cells, knockdown of ZNF281 exerted an inhibitory effect on ferroptosis and ECM synthesis. We demonstrated the targeted binding of tRF3-IleAAT to the 3'UTR of ZNF281. In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.


Assuntos
Nefropatias Diabéticas , Matriz Extracelular , Ferroptose , Animais , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Nefropatias Diabéticas/metabolismo , Matriz Extracelular/metabolismo , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Humanos , Células Mesangiais/metabolismo
19.
J Pharm Pharmacol ; 76(5): 559-566, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38215001

RESUMO

Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs' intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.


Assuntos
Angelica , Ácidos Cumáricos , Cumarínicos , Furocumarinas , Absorção Intestinal , Isoflavonas , Furocumarinas/farmacologia , Humanos , Células CACO-2 , Angelica/química , Absorção Intestinal/efeitos dos fármacos , Isoflavonas/farmacologia , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Transporte Biológico , Ocludina/metabolismo , Raízes de Plantas
20.
Plant Cell Physiol ; 65(1): 95-106, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-37874689

RESUMO

The spatial separation of photosystems I and II (PSI and PSII) is thought to be essential for efficient photosynthesis by maintaining a balanced flow of excitation energy between them. Unlike the thylakoid membranes of plant chloroplasts, cyanobacterial thylakoids do not form tightly appressed grana stacks that enforce strict lateral separation. The coexistence of the two photosystems provides a ground for spillover-excitation energy transfer from PSII to PSI. Spillover has been considered as a pathway of energy transfer from the phycobilisomes to PSI and may also play a role in state transitions as means to avoid overexcitation of PSII. Here, we demonstrate a significant degree of energy spillover from PSII to PSI in reconstituted membranes and isolated thylakoid membranes of Thermosynechococcus (Thermostichus) vulcanus and Synechocystis sp. PCC 6803 by steady-state and time-resolved fluorescence spectroscopy. The quantum yield of spillover in these systems was determined to be up to 40%. Spillover was also found in intact cells but to a considerably lower degree (20%) than in isolated thylakoid membranes. The findings support a model of coexistence of laterally separated microdomains of PSI and PSII in the cyanobacterial cells as well as domains where the two photosystems are energetically connected. The methodology presented here can be applied to probe spillover in other photosynthetic organisms.


Assuntos
Synechocystis , Tilacoides , Tilacoides/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Fotossíntese , Complexo de Proteína do Fotossistema I/metabolismo , Synechocystis/metabolismo
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