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1.
J Environ Sci (China) ; 149: 628-637, 2025 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39181673

RESUMEN

Phthalate esters (PAEs), recognized as endocrine disruptors, are released into the environment during usage, thereby exerting adverse ecological effects. This study investigates the occurrence, sources, and risk assessment of PAEs in surface water obtained from 36 sampling points within the Yellow River and Yangtze River basins. The total concentration of PAEs in the Yellow River spans from 124.5 to 836.5 ng/L, with Dimethyl phthalate (DMP) (75.4 ± 102.7 ng/L) and Diisobutyl phthalate (DiBP) (263.4 ± 103.1 ng/L) emerging as the predominant types. Concentrations exhibit a pattern of upstream (512.9 ± 202.1 ng/L) > midstream (344.5 ± 135.3 ng/L) > downstream (177.8 ± 46.7 ng/L). In the Yangtze River, the total concentration ranges from 81.9 to 441.6 ng/L, with DMP (46.1 ± 23.4 ng/L), Diethyl phthalate (DEP) (93.3 ± 45.2 ng/L), and DiBP (174.2 ± 67.6 ng/L) as the primary components. Concentration levels follow a midstream (324.8 ± 107.3 ng/L) > upstream (200.8 ± 51.8 ng/L) > downstream (165.8 ± 71.6 ng/L) pattern. Attention should be directed towards the moderate ecological risks of DiBP in the upstream of HH, and both the upstream and midstream of CJ need consideration for the moderate ecological risks associated with Di-n-octyl phthalate (DNOP). Conversely, in other regions, the associated risk with PAEs is either low or negligible. The main source of PAEs in Yellow River is attributed to the release of construction land, while in the Yangtze River Basin, it stems from the accumulation of pollutants in lakes and forests discharged into the river. These findings are instrumental for pinpointing sources of PAEs pollution and formulating control strategies in the Yellow and Yangtze Rivers, providing valuable insights for global PAEs research in other major rivers.


Asunto(s)
Monitoreo del Ambiente , Ésteres , Ácidos Ftálicos , Ríos , Contaminantes Químicos del Agua , Ácidos Ftálicos/análisis , Ríos/química , China , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Ésteres/análisis , Disruptores Endocrinos/análisis , Dibutil Ftalato/análisis , Dibutil Ftalato/análogos & derivados
2.
Biomaterials ; 313: 122775, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39241549

RESUMEN

Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.


Asunto(s)
Células Madre Mesenquimatosas , MicroARNs , Infarto del Miocardio , Nanopartículas , Infarto del Miocardio/terapia , Animales , Nanopartículas/química , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Recuperación de la Función , Trasplante de Células Madre Mesenquimatosas/métodos , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones , Microburbujas , Ondas Ultrasónicas
3.
Sci Total Environ ; : 176434, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307363

RESUMEN

With the regulation and phase-out of conventional per- and polyfluoroalkyl substances (PFAS), there is a growing trend towards seeking alternatives that are less toxic and less persistent. Hexafluoropropylene oxide trimer acid (HFPO-TA) is one of the alternatives to perfluorooctanoic acid (PFOA), the latter being widely present in the environment globally. However, there is limited information regarding the biological toxicity of HFPO-TA to aquatic organisms. In this study, the freshwater benthic amphipod, Hyalella azteca, was used to assess the acute and chronic toxicity of HFPO-TA in both water and sediment. HFPO-TA was found to be more toxic to H. azteca than PFOA, as indicated by greater production of reactive oxygen species (p < 0.05) and increasing catalase activity (p < 0.05). In addition, exposure to HFPO-TA affected the swimming behavior and the acetylcholinesterase (AChE) activity of the amphipod. Molecular docking models revealed that HFPO-TA can bind to AChE with a stronger binding affinity than PFOA. Furthermore, an integrated biomarker response index indicated that environmentally relevant concentration (1-100 µg/L) of HFPO-TA may cause toxicity to H. azteca, encompassing oxidative stress and neurotoxicity. This study provides new insights into the toxicity mechanisms of HFPO-TA and is valuable for assessing the ecological safety of this compound.

4.
Neurobiol Dis ; : 106673, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307401

RESUMEN

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited and lethal neurodegenerative disease caused by the abnormal expansion of CAG repeats in the ATAXIN-1 (ATXN1) gene. Pathological studies identified dysfunction and loss of motor neurons (MNs) in the brain stem and spinal cord, which are thought to contribute to premature lethality by affecting the swallowing and breathing of SCA1 patients. However, the molecular and cellular mechanisms of MN pathogenesis remain unknown. To study SCA1 pathogenesis in human MNs, we differentiated induced pluripotent stem cells (iPSCs) derived from SCA1 patients and their unaffected siblings into MNs. We examined proliferation of progenitor cells, neurite outgrowth, spontaneous and glutamate-induced calcium activity of SCA1 MNs to investigate cellular mechanisms of pathogenesis. RNA sequencing was then used to identify transcriptional alterations in iPSC-derived MN progenitors (pMNs) and MNs which could underlie functional changes in SCA1 MNs. We found significantly decreased spontaneous and evoked calcium activity and identified dysregulation of genes regulating calcium signaling in SCA1 MNs. These results indicate that expanded ATXN1 causes dysfunctional calcium signaling in human MNs.

5.
Sci Total Environ ; 953: 176174, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39260514

RESUMEN

While large-scale vegetation greening in China has substantially influenced global vegetation dynamics, the specific impact of this restoration on water use efficiency (WUE) remained inadequately understood. This study employed both the Geodetector and structural equation modeling (SEM) methods, utilizing the Lund-Potsdam-Jena (LPJ) Global Dynamic Vegetation Model, to explore the contributions of various driving factors to China's potential vegetation WUE from 1982 to 2019. The results indicated: (1) there existed considerable further potential for vegetation recovery nationwide. Among them, the Loess Plateau, Inner Mongolia Plateau, and northern Xinjiang had relatively high potential for vegetation recovery. This potential was further amplified by the significant prospects for enhancing WUE in these areas; (2) The application of the Geodetector method revealed that the normalized difference vegetation index (NDVI) explained over 40 % of the variation in potential vegetation WUE in China, exerting a greater influence than climatic factors. In arid/semi-arid regions, precipitation (PRE), NDVI, and vapor pressure deficit (VPD) significantly influenced WUE. Temperature (TEM) was the dominant factor affecting WUE in humid and humid/semi-humid regions; (3) Utilizing the SEM analysis method, it was evident that NDVI exerted the most substantial direct positive influence on potential vegetation WUE in China, whereas VPD and PRE had notable negative impacts. In arid/semi-arid regions, PRE emerged as the primary determinant of WUE. Conversely, in regions where water resources were not limiting, TEM and VPD exerted a more pronounced influence on potential vegetation WUE. This indicated that while vegetation restoration generally enhanced potential vegetation WUE, other factors such as PRE, TEM, and VPD played critical roles in different climatic zones, shaping the regional variations in WUE.

6.
Nat Commun ; 15(1): 8015, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271695

RESUMEN

Realizing an efficient turnover frequency in the acidic oxygen evolution reaction by modifying the reaction configuration is crucial in designing high-performance single-atom catalysts. Here, we report a "single atom-double site" concept, which involves an activatable inert manganese atom redox chemistry in a single-atom Ru-Mn dual-site platform with tunnel Ni ions as the trigger. In contrast to conventional single-atom catalysts, the proposed configuration allows direct intramolecular oxygen coupling driven by the Ni ions intercalation effect, bypassing the secondary deprotonation step instead of the kinetically sluggish adsorbate evolution mechanism. The strong bonding of Ni ions activates the inert manganese terminal groups and inhibits the cross-site disproportionation process inherent in the Mn scaffolding, which is crucial to ensure the dual-site platform. As a result, the single-atom Ru-Ni-Mn octahedral molecular sieves catalyst delivers a low overpotential, adequate mass activity and good stability.

7.
BMC Oral Health ; 24(1): 1079, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272063

RESUMEN

OBJECTIVE: To investigate the current state of oral frailty in oldely patients with require dental implants, analyze influencing factors in the characteristics of oral frailty across different patient categories, and provide a reference for clinical staff to identify high-risk groups and develop proactive management strategies. METHODS: Between January 2024 and March 2024, 654 patients with dental implants were selected using convenience sampling from six secondary and tertiary stomatological hospitals in Jiangsu and Zhejiang provinces. Data were collected via a general information questionnaire and the Oral Frailty Index-8. The latent profiles of oral frailty were examined, and univariate and Logistic regression analyses were conducted to determine the impact of various factors on these profiles. RESULTS: In this cross-sectional study, 605 valid questionnaires were returned, yielding an effective rate of 92.58%. The mean oral frailty score was 6.64 ± 1.21, with the sample comprising 223 males and 382 females, averaging 72.54 ± 6.33 years old. Oral frailty was categorized into three latent profiles: high (20.50%), moderate (53.72%), and low (25.78%) frailty groups. Factor analysis indicated that age, gender, education level, family income, number of implants, and dyslipidemia significantly predicted the classification of these profiles (P < 0.05). CONCLUSION: Oral frailty in oldely patients with dental implants exhibits heterogeneity and is influenced by age, sex, education level, family income, number of implants, and dyslipidemia. Clinical staff should recognize the characteristics of different patient categories and implement proactive measures for those at high risk of oral frailty to enhance their quality of life.


Asunto(s)
Implantes Dentales , Fragilidad , Humanos , Masculino , Femenino , Estudios Transversales , Anciano , Fragilidad/complicaciones , Encuestas y Cuestionarios , Factores de Riesgo , Anciano de 80 o más Años , China , Persona de Mediana Edad , Anciano Frágil , Factores de Edad
8.
Materials (Basel) ; 17(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39274613

RESUMEN

High-entropy alloys (HEA) as a kind of new binder for cemented carbide have garnered significant attention. In this work, WC/(17~25 wt.%)Al0.5CoCrFeNiTi0.5 cemented carbides were prepared by hot pressing sintering (HPS), and the reactions between WC powder and Al0.5CoCrFeNiTi0.5 powder during hot pressing sintering were elucidated. It found that different from traditional Co binder, the Al0.5CoCrFeNiTi0.5 binder effectively inhibited WC grain growth. During HPS, the decomposed W and C atoms from WC diffused into the Al0.5CoCrFeNiTi0.5 binder, reacted with the elements in the binder, and then formed the M(Co, Fe, Ni)3W3C phase. The back-diffusion of W and C atoms to WC grains was restricted by the Al0.5CoCrFeNiTi0.5 alloy and inhibited them from re-precipitating onto the large undissolved WC grains. As a result, the average size of WC grains in the cemented carbides was less than 200 nm. This work bright new insight into the grain refinement mechanisms of WC cemented carbide with HEA binder and provide a guidance for designing performance-stable WC/HEA cemented carbide and promoting their application.

9.
Inorg Chem ; 63(37): 17116-17126, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39231020

RESUMEN

Precisely tuning how and where a reaction occurs in a one-step selective system is important but challenging owing to the similar electronic environments in multiple active sites. In this work, highly selective and effective reaction sites were obtained by generating copper coordination polymers (Cu-CP) of a range of sizes and morphologies, from bulk solid crystals (1) to uniform nanosphere structures (1a), by controlling the amount of surfactant hexadecyl trimethylammonium bromide (CTAB). The results indicated that the morphology and size of the uniform nanosphere structures were affected by the proportion of CTAB; uniform distribution of nanosphere structures was achieved with a premade building carrier when the content of CTAB was 0.005 mmol, generating a well-established platform. Photocatalytic cadmium sulfide (CdS) was then immobilized on the surface of the premade platform unit 1a through an in situ process to generate CdS@1a composites with well-dispersed catalytic CdS active sites. Furthermore, the well-defined CdS@1a composite platform was utilized as photocatalysts to explore the selective one-step depolymerization reaction under blue-light irradiation. Notably, the CdS0.149@1a composite, which featured a unique structure with evenly dispersed, closely spaced catalytic sites, exhibiting remarkable photoelectrochemical behaviors for selective one-step depolymerization of lignin model substances to aromatic monomer phenol and acetophenone framework products. This work demonstrates the use of an inherently morphological process to construct outstanding photocatalysts that could enable a wide range of photocatalytic reactions.

10.
Expert Opin Drug Saf ; : 1-7, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39242080

RESUMEN

BACKGROUND: Migraine, a prevalent neurovascular disorder, can significantly disrupt an individual's daily life. Atogepant (AGN-241689), an orally administered small-molecule drug classified as a calcitonin gene-related peptide receptor antagonist, is utilized for prophylactic migraine treatment. The objective of this study was to investigate adverse events (AEs) associated with atogepant through data mining in the FDA Adverse Event Reporting System (FAERS) to enhance clinical safety. METHODS: Data for atogepant were obtained from the FAERS database covering Q3 2021 through Q4 2023. Disproportionality analysis was employed to quantify relevant AEs associated with atogepant. Reported Ratio of Ratios (ROR) was utilized for identifying risk signals within the FAERS data. This methodology relies on the System Organ Class (SOC) and Preferred Terminology (PT) of the Medical Dictionary for Regulatory Activities (MedDRA). RESULTS: From the FAERS database, a collection of 7,991,243 reports was obtained. Among these reports, a subset of 3015 was identified as 'primary suspected (PS)' AEs specifically related to atogepant. AEs induced by atogepant were observed across 27 organ systems. A total of 48 significantly disproportionate Preferred Terminologies (PTs) meeting all four algorithms were identified. CONCLUSION: Our study has identified adverse events (AEs) associated with atogepant, potentially providing crucial support for the clinical monitoring and risk identification of atogepant.

11.
Nat Struct Mol Biol ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304765

RESUMEN

Human silencers have been shown to regulate developmental gene expression. However, the functional importance of human silencers needs to be elucidated, such as whether they can form 'super-silencers' and whether they are linked to cancer progression. Here, we show two silencer components of the FGF18 gene can cooperate through compensatory chromatin interactions to form a super-silencer. Double knockout of two silencers exhibited synergistic upregulation of FGF18 expression and changes in cell identity. To perturb the super-silencers, we applied combinational treatment of an enhancer of zeste homolog 2 inhibitor GSK343, and a repressor element 1-silencing transcription factor inhibitor, X5050 ('GR'). Interestingly, GR led to severe loss of topologically associated domains and loops, which were associated with reduced CTCF and TOP2A mRNA levels. Moreover, GR synergistically upregulated super-silencer-controlled genes related to cell cycle, apoptosis and DNA damage, leading to anticancer effects in vivo. Overall, our data demonstrated a super-silencer example and showed that GR can disrupt super-silencers, potentially leading to cancer ablation.

12.
Phytomedicine ; 135: 156008, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39305746

RESUMEN

BACKGROUND: Sarcandra is one of the five genera of Chloranthaceae, which has a long history of medicinal use and high medicinal value, with excellent therapeutic effects on liver cancer, pneumonia, colitis, bone fractures, and dysentery. Among its species, Sarcandra glabra (Thunb.) Nakai has been extensively utilized in diverse compound formulations, toothpaste, tea, daily commodities, as well as health supplements. Therefore, in terms of its medicinal properties and effectiveness, the genus has considerable potential for development and utilization. PURPOSE: This paper presents a systematic review of the botany, ethnomedicine, phytochemistry, pharmacology, and toxicology of Sarcandra plants, aiming to deepen our understanding of Sarcandra properties further, to provide a reference for the rational utilization of Sarcandra plant resources, and at the same time laying a foundation for the development of new medicines and the study of natural products. METHODS: In this paper, we collected information about Sarcandra species through PubMed, Science Direct, Web of Science, Baidu Scholar, Google Scholar, CNKI, and other databases using the keywords Sarcandra, botany, traditional uses, chemical compounds, pharmacology and toxicology. Its botanical-related information was obtained through the Flora of China (www.iplant.cn). RESULTS: Three species of Sarcandra plants worldwide are distributed from eastern Asia to India. This genus has a long history of medicinal uses, high medicinal value, and a wide range of applications. At present, 462 compounds have been isolated and identified from Sarcandra plants, and their diversity contributes to the diversity of the pharmacological effects of Sarcandra plants. Numerous studies have shown that Sarcandra plants exhibit significant antitumor, antibacterial, anti-inflammatory, antimalarial, antiviral, antithrombocytopenia, immunomodulatory, antioxidant, hepatoprotective, hypoglycemic and hypolipidemic effects, with low toxicity and side effects. However, most studies have focused on Sarcandra glabra (Thunb.) Nakai and studies on other plants of the genus have yet to be explored. CONCLUSIONS: Sarcandra plants have a wide range of clinical uses and diverse chemical compounds. However, the main research has been concentrated on Sarcandra glabra (Thunb.) Nakai, and future research should explore the medicinal properties of other Sarcandra plants to expand their potential clinical applications. Meanwhile, the pharmacological activities of compounds from Sarcandra species need to be studied in greater depth and detail to provide an appropriate scientific basis for developing new drugs and natural product research.

13.
Metab Eng ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39305946

RESUMEN

The anaerobic bacterium Anaerocellum (f. Caldicellulosiruptor) bescii natively ferments the carbohydrate content of plant biomass (including microcrystalline cellulose) into predominantly acetate, H2, and CO2, and smaller amounts of lactate, alanine and valine. While this extreme thermophile (growth Topt 78°C) is not natively ethanologenic, it has been previously metabolically engineered with this property, albeit initially yielding low solvent titers (∼ 15 mM). Herein we report significant progress on improving ethanologenicity in A. bescii, such that titers above 130 mM have now been achieved, while concomitantly improving selectivity by minimizing acetate formation. Metabolic engineering progress has benefited from improved molecular genetic tools and better understanding of A. bescii growth physiology. Heterologous expression of a mutated thermophilic alcohol dehydrogenase (AdhE) modified for co-factor requirement, coupled with bioreactor operation strategies related to pH control, have been key to enhanced ethanol generation and fermentation product specificity. Insights gained from metabolic modeling of A. bescii set the stage for its further improvement as a metabolic engineering platform.

14.
Pharmacol Res ; : 107418, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39306022

RESUMEN

The ZDHHC13/ZDHHC17 subfamily belongs to the zinc finger DHHC-domain containing (ZDHHC) family, including ZDHHC13 and ZDHHC17. Recent studies have shown that the ZDHHC13/ZDHHC17 subfamily is involved in various pathological and physiological processes, including S-palmitoylation, Mg2+ transport, and CALCOCO1-mediated Golgiphagy. Moreover, the ZDHHC13/ZDHHC17 subfamily plays a crucial role in the occurrence and development of many diseases, including Huntington disease (HD), osteoporosis, atopic dermatitis, diabetes, and cancer. In the present review, we describe the distribution, structure, and post-translational modifications (PTMs) of the ZDHHC13/ZDHHC17 subfamily. Moreover, we effectively summarize the biological functions and associated diseases of this subfamily. Given the pleiotropy of the ZDHHC13/ZDHHC17 subfamily, it is imperative to conduct further research on its members to comprehend the pertinent pathophysiological mechanisms and to devise tactics for managing and controlling various diseases.

15.
Chemosphere ; 365: 143286, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265738

RESUMEN

Facing the increasingly prominent tetracycline pollution and the resulting environmental problems, how to find environmental and efficient treatment means is one of the current research hotspots. In this study, the laccase surface-display technology for tetracycline treatment was investigated. Via study, the type of anchoring protein had a minor influence on the laccase ability, while the type of laccase showed a major impact. Bacillus subtilis spore coat protein (CotA) exhibited higher laccase activity, stability, and efficiency in degrading tetracycline than Pleurotus ostreatus laccase 6 (Lacc6). The superiority of bacterial laccase over fungal laccase was elucidated from the perspective of crystal structure. Besides, a variety of technical means were used to verify the success of surface-display. pGSA-CotA surface-displayed bacteria exhibited good tolerance to high temperature, pH, and various heavy metals. Importantly, surface-displayed bacteria showed faster degradation efficiency and better treatment effects than the intracellular expression bacteria in tetracycline degradation. This implies that surface display technology has greater potential for laccase-mediated environmental remediation. Due to the adverse impacts of tetracycline on soil enzyme activity and microorganisms, our study found that pGSA-CotA surface-displayed bacteria can alleviate tetracycline stress in soil and partially activate the soil, thereby increasing soil enzyme activity and certain nitrogen cycling genes.

16.
J Neuroinflammation ; 21(1): 231, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300526

RESUMEN

Viral encephalitis is characterized by inflammation of the brain parenchyma caused by a variety of viruses, among which the Japanese encephalitis (JE) virus (JEV) is a typical representative arbovirus. Neuronal death, neuroinflammation, and breakdown of the blood brain barrier (BBB) constitute vicious circles of JE progression. Currently, there is no effective therapy to prevent this damage. Growth arrest specific gene 6 (GAS6) is a secreted growth factor that binds to the TYRO3, AXL, and MERTK (TAM) family of receptor tyrosine kinases and has been demonstrated to participate in neuroprotection and suppression of inflammation in many central nervous system (CNS) diseases which has great potential for JE intervention. In this study, we found that GAS6 expression in the brain was decreased and was reversely correlated with viral load and neuronal loss. Mice with GAS6/TAM signalling deficiency showed higher mortality and accelerated neuroinflammation during peripheral JEV infection, accompanied by BBB breakdown. GAS6 directly promoted the expression of tight junction proteins in bEnd.3 cells and strengthened BBB integrity, partly via AXL. Mice administered GAS6 were more resistant to JEV infection due to increased BBB integrity, as well as decreased viral load and neuroinflammation. Thus, targeted GAS6 delivery may represent a strategy for the prevention and treatment of JE especially in patients with impaired BBB.


Asunto(s)
Modelos Animales de Enfermedad , Encefalitis Japonesa , Péptidos y Proteínas de Señalización Intercelular , Enfermedades Neuroinflamatorias , Animales , Ratones , Encefalitis Japonesa/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Enfermedades Neuroinflamatorias/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Ratones Endogámicos C57BL , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Ratones Noqueados , Tirosina Quinasa del Receptor Axl
17.
Arch Biochem Biophys ; : 110138, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39303929

RESUMEN

INTRODUCTION: Local exposure to ionizing radiation (IR) can induce changes in biological processes in distant tissues and organs. Exosomes are nanoscale vesicles that transport biomolecules, mediate communication between cells and tissues, and can affect the abscopal effects of radiotherapy. METHODS: Mice were treated with 8.0 Gy doses of chest and abdomen IR, after which serum samples were taken 24 h after exposure. Their serum exosomes were then isolated via ultracentrifugation and the small RNA portions were extracted for sequencing and bioinformatic analysis. Exosomes were injected intravenously into the mice to assess their ability to cross the blood-brain barrier (BBB). Glioma cells and gliomal stem cells (GSCs) were examined for malignant biological behaviors, stemness, and tumorigenic capacity after co-culturing with different types of exosomes. RESULTS: We found that serum exosomes crossed the BBB in mice after local IR exposure-which induced decreases in the expression of BBB tight-junction proteins and increased brain endothelial cell apoptosis. Exosomes from the exposed groups promoted malignant biological behaviors, stemness, and tumorigenic capacity in glioma cells and GSCs by upregulating the expression of SOS1. Phospho-MEK1/2 and Phospho-ERK1/2, of the MAPK signaling pathway, were found to be up-regulated in cells that were co-cultured with the exposing groups of the exosomes. Further analyses demonstrated that differentially expressed levels of miR-93-5p in mouse serum exosomes regulated the cellular expression of SOS1. CONCLUSION: Following local IR exposure, serum exosomes cross the BBB to promote the progression of distant gliomas. Exosomal microRNAs play an important role in this process.

18.
Pharmacol Res ; 208: 107392, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39233057

RESUMEN

AIMS: Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM) without curative interventions currently. Huperzine A (Hup A), a natural alkaloid, has demonstrated significant hypoglycemic and anti-inflammatory effects. We aim to investigate the protective effects of Hup A on DN and explore the underlying mechanisms METHODS: We applied STZ induced diabetic rats as DN model and leveraged combination analysis of the transcriptome, metabolome, microbiome, and network pharmacology (NP). The total effect of Hup A on DN was detected (i.e. urine protein, renal tissue structure) and the differential genes were further verified at the level of diabetic patients, db/db mice and cells. Clinical data and small interfering RNA (siRNA)-Apoe were adopted. RESULTS: Hup A alleviated kidney injury in DN rats. Transcriptomics data and Western blot indicated that the improvement in DN was primarily associated with Apoe and Apoc2. Additionally, metabolomics data demonstrated that DN-induced lipid metabolism disruption was regulated by Hup A, potentially involving sphingosine. Hup A also enriched microbial diversity and ameliorated DN-induced microbiota imbalance. Spearman's correlation analysis demonstrated significant associations among the transcriptome, metabolome, and microbiome. Apoe level was positively correlated with clinical biomarkers in DN patients. Si-Apoe also played protective role in podocytes. NP analysis also suggested that Hup A may treat DN by modulating lipid metabolism, microbial homeostasis, and apoptosis, further validating our findings. CONCLUSIONS: Collectively, we provide the first evidence of the therapeutic effect of Hup A on DN, indicating that Hup A is a potential drug for the prevention and treatment of DN.


Asunto(s)
Alcaloides , Apolipoproteínas E , Diabetes Mellitus Experimental , Nefropatías Diabéticas , Ratas Sprague-Dawley , Sesquiterpenos , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/genética , Animales , Alcaloides/farmacología , Alcaloides/uso terapéutico , Masculino , Humanos , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Apolipoproteínas E/genética , Ratas , Ratones , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Transcriptoma/efectos de los fármacos , Ratones Endogámicos C57BL , Farmacología en Red , Metabolómica , Persona de Mediana Edad , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Femenino
19.
Front Plant Sci ; 15: 1425798, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309179

RESUMEN

Introduction: Clubroot disease is a devastating soil borne disease caused by infection with Plasmodiophora brassicae, which primarily affects cruciferous plants. The microbial diversity of the soil is an essential indicator of its quality. Methods: This study measured the physicochemical properties of the soil to study the effect of its microbial diversity on the infection of oilseed rape with P. brassicae. High-throughput sequences of the soil bacteria and fungi in the inter-root soils of P. brassicae were analyzed under different treatment conditions. Results: In the study, it was found that the efficiency of strain X216 in preventing and controlling the root disease of rapeseed was positively correlated with the amount of solution used to irrigate the root system. The results of the greenhouse and field trials showed that the efficiency of strain X216 against the root disease of rapeseed was 43.16% in the field and 62.14% in the greenhouse. Proteobacteria, Chloroflexi, Rozellomycota, and Basidiomycota are critical phylum in the development of clubroot disease. The application of biocontrol increased the relative abundance of Actinobacteria, Bacillus, Mesorhizobium, Mycobacterium, Streptomyces and Filobasidium, which affected the structure and abundance of microbial communities. A principal coordinate analysis showed that the microbial structure in the soil varied substantially in the bacterial community, and there was no significant difference in soil structure in the fungal community. Discussion: The occurrence of clubroot disease affected the structure of inter-root microbial community composition in the soil, which resulted in a decrease in its community diversity. The application of the biocontrol bacterium X216 increased the soil microbial diversity. It effectively reduced the occurrence of P. brassicae, and this study provides a basis to study the microbial diversity in cruciferous crops.

20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(6): 848-855, 2024 Jun 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39311780

RESUMEN

This report describes a case of maturity-onset diabetes of the young (MODY) type 3 (MODY3) complicated with type 5 (MODY5), including the patient's clinical features, diagnosis, and treatment, and reviews relevant literature. Using next-generation sequencing of MODY (types 1-14) gene exons and Sanger sequencing for verification, the patient and her mother were assessed. Based on the clinical phenotype and genetic test results, the patient was diagnosed as MODY3 combined with MODY5. Treatment included insulin and linagliptin, with monitoring of blood glucose changes. Clinicians should enhance their understanding of MODY clinical phenotypes. In adolescents with diabetes who have congenital pancreatic and renal developmental defects, elevated high-density lipoprotein cholesterol, no spontaneous ketosis, insulin secretion defects, negative pancreatic autoantibodies, no significant insulin resistance, and who are not obese, gene testing should be conducted to screen for MODY. Accurate diagnosis and personalized treatment can aid in achieving glycemic control, improving quality of life, and optimizing reproductive planning.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Femenino , Adolescente , Insulina/uso terapéutico , Glucemia/análisis , Glucemia/metabolismo
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