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1.
Colloids Surf B Biointerfaces ; 243: 114156, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39137532

RESUMO

Bacteria and bacterial components have been widely used as bionanocarriers to deliver drugs to treat tumors. In this study, we isolated bacterial outer membrane vesicles (OMVs) with good stability and high yield for macrophage polarization and cell recruitment. Using ultrasound baths, these bacterial OMVs were combined with curcumin nanoparticles (OMV CUR NPs), following which these nanoparticles were modified with bovine serum albumin (BSA) to achieve high biosafety and tumor-targeting effects. The particle size, PDI, and zeta potential of the BSA-OMV CUR NPs were 157.9 nm, 0.233, and -15.1 mV, respectively. The BSA-OMV CUR NPs exhibited high storage stability, low cytotoxicity, sustained release, enhanced cellular uptake of CUR, induction of tumor cell apoptosis, and inhibition of tumor cell proliferation and migration. By determining the survival rate, body length, heart rate, head size, eye size, and pericardium size of the zebrafish, we found that the BSA-OMV CUR NPs were safe for application in vivo. Moreover, an increase in antiproliferation, antiangiogenic and antimetastatic effects of BSA-OMV CUR NPs was demonstrated in wild-type and transgenic tumor-transplanted zebrafish embryos.

2.
Eur Spine J ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073460

RESUMO

OBJECTIVE: This study aimed to develop and validate a machine learning (ML) model to predict high-grade heterotopic ossification (HO) following Anterior cervical disc replacement (ACDR). METHODS: Retrospective review of prospectively collected data of patients undergoing ACDR or hybrid surgery (HS) at a quaternary referral medical center was performed. Patients diagnosed as C3-7 single- or multi-level cervical disc degeneration disease with > 2 years of follow-up and complete pre- and postoperative radiological imaging were included. An ML-based algorithm was developed to predict high grade HO based on perioperative demographic, clinical, and radiographic parameters. Furthermore, model performance was evaluated according to discrimination and overall performance. RESULTS: In total, 339 ACDR segments were included (61.65% female, mean age 45.65 ± 8.03 years). Over 45.65 ± 8.03 months of follow-up, 48 (14.16%) segments developed high grade HO. The model demonstrated good discrimination and overall performance according to precision (High grade HO: 0.71 ± 0.01, none-low grade HO: 0.85 ± 0.02), recall (High grade HO: 0.68 ± 0.03, none-low grade HO: 0.87 ± 0.01), F1-score (High grade HO: 0.69 ± 0.02, none-low grade HO: 0.86 ± 0.01), and AUC (0.78 ± 0.08), with lower prosthesis­endplate depth ratio, higher height change, male, and lower postoperative-shell ROM identified as the most important predictive features. CONCLUSION: Through an ML approach, the model identified risk factors and predicted development of high grade HO following ACDR with good discrimination and overall performance. By addressing the shortcomings of traditional statistics and adopting a new logical approach, ML techniques can support discovery, clinical decision-making, and intraoperative techniques better.

5.
Front Mol Neurosci ; 17: 1375925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807922

RESUMO

Zinc transporter 3 (ZnT3) is abundantly expressed in the brain, residing in synaptic vesicles, where it plays important roles in controlling the luminal zinc levels. In this study, we found that ZnT3 knockout in mice decreased zinc levels in the hippocampus and cortex, and was associated with progressive cognitive impairments, assessed at 2, 6, and 9-month of age. The results of Golgi-Cox staining demonstrated that ZnT3 deficiency was associated with an increase in dendritic complexity and a decrease in the density of mature dendritic spines, indicating potential synaptic plasticity deficit. Since ZnT3 deficiency was previously linked to glucose metabolism abnormalities, we tested the expression levels of genes related to insulin signaling pathway in the hippocampus and cortex. We found that the Expression of glucose transporters, GLUT3, GLUT4, and the insulin receptor in the whole tissue and synaptosome fraction of the hippocampus of the ZnT3 knockout mice were significantly reduced, as compared to wild-type controls. Expression of AKT (A serine/threonine protein kinase) and insulin-induced AKT phosphorylation was also reduced in the hippocampus of ZnT3 knockout mice. We hypothesize that the ZnT3 deficiency and reduced brain zinc levels may cause cognitive impairment by negatively affecting glycose metabolism via decreased expression of key components of insulin signaling, as well as via changes in synaptic plasticity. These finding may provide new therapeutic target for treatments of neurodegenerative disorders.

6.
Neural Regen Res ; 19(9): 2075-2080, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38227538

RESUMO

JOURNAL/nrgr/04.03/01300535-202409000-00041/figure1/v/2024-01-16T170235Z/r/image-tiff The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

7.
J Sci Food Agric ; 104(4): 2449-2457, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37961839

RESUMO

BACKGROUND: The shortage of water resources and the increase of greenhouse gas emissions from soil seriously restrict the sustainable development of agriculture. Under the premise of ensuring a stable yield of winter wheat through a reasonable irrigation scenario, identifying a suitable straw returning method will have a positive effect on agricultural carbon sequestration and emission reduction in North China Plain. RESULTS: Straw burying (SR) and straw mulching (SM) were adopted based on traditional tillage under in the winter wheat growing season of 2020-2021 and 2021-2022. Three irrigation scenarios were used for each straw returning method: no irrigation (I0), irrigation 60 mm at jointing stage (I1), and irrigation of 60 mm each at the jointing and heading stages (I2). Soil moisture, soil respiration rate, cumulative soil CO2 emissions, yield, water use efficiency (WUE) and soil CO2 emission efficiency (CEE) were mainly studied. The results showed that, compared to SM, SR improved the utilization of soil water and enhanced soil carbon sequestration. SR reduced soil respiration rate and cumulative soil CO2 emissions in two winter wheat growing seasons, and increased yield by increasing spike numbers. In addition, with an increase in the amount of irrigation, soil CO2 emissions and yield increased. Under SR-I1 treatment, WUE and CEE were the highest. SR-I1 increases crop yields at the same time as reducing soil CO2 emissions. CONCLUSION: The combination of SR and irrigation 60 mm at jointing stage is a suitable straw returning irrigation scenario, which can improve water use and reduce soil CO2 emission in NCP. © 2023 Society of Chemical Industry.


Assuntos
Solo , Triticum , Estações do Ano , Dióxido de Carbono/análise , Água , Carbono , Agricultura/métodos , China
8.
J Hazard Mater ; 465: 133183, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38070267

RESUMO

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) are widely distributed brominated flame retardants. While TBBPA has been demonstrated to stimulate adipogenesis, TBBPS is also under suspicion for potentially inducing comparable effects. In this study, we conducted a non-targeted metabolomics to examine the metabolic changes in 3T3-L1 cells exposed to an environmentally relevant dose of TBBPA or TBBPS. Our findings revealed that 0.1 µM of both TBBPA and TBBPS promoted the adipogenesis of 3T3-L1 preadipocytes. Multivariate analysis showed significant increases in glycerophospholipids, sphingolipids, and steroids relative levels in 3T3-L1 cells exposed to TBBPA or TBBPS at the final stage of preadipocyte differentiation. Metabolites set composed of glycerophospholipids was found to be highly effective predictors of adipogenesis in 3T3-L1 cells exposed to TBBPA or TBBPS (revealed from the receiver operating characteristic curve with an area under curve > 0.90). The results from metabolite set enrichment analysis suggested both TBBPA and TBBPS exposures significantly perturbed steroid biosynthesis in adipocytes. Moreover, TBBPS additionally disrupted the sphingolipid metabolism in the adipocytes. Our study presents new insights into the obesogenic effects of TBBPS and provides valuable information about the metabolites associated with adipogenesis induced by TBBPA or TBBPS.


Assuntos
Adipogenia , Metabolismo dos Lipídeos , Bifenil Polibromatos , Animais , Camundongos , Células 3T3-L1 , Diferenciação Celular , Glicerofosfolipídeos/farmacologia
10.
Pharmaceutics ; 15(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37896250

RESUMO

Bacteria and bacterial components possess multifunctional properties, making them attractive natural bio-nanocarriers for cancer diagnosis and targeted treatment. The inherent tropic and motile nature of bacteria allows them to grow and colonize in hypoxic tumor microenvironments more readily than conventional therapeutic agents and other nanomedicines. However, concerns over biosafety, limited antitumor efficiency, and unclear tumor-targeting mechanisms have restricted the clinical translation and application of natural bio-nanocarriers based on bacteria and bacterial components. Fortunately, bacterial therapies combined with engineering strategies and nanotechnology may be able to reverse a number of challenges for bacterial/bacterial component-based cancer biotherapies. Meanwhile, the combined strategies tend to enhance the versatility of bionanoplasmic nanoplatforms to improve biosafety and inhibit tumorigenesis and metastasis. This review summarizes the advantages and challenges of bacteria and bacterial components in cancer therapy, outlines combinatorial strategies for nanocarriers and bacterial/bacterial components, and discusses their clinical applications.

11.
Cell Signal ; 112: 110914, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37806541

RESUMO

Butyrophilin subfamily 3 member A3 (BTN3A3) is a member of the immunoglobulin superfamily and functions as a tumor suppressor in multiple cancer types. Our study has revealed that in clear cell renal cell carcinoma (ccRCC), patients who express high levels of BTN3A3 experience longer survival times than those with lower expression. Further, we have observed that BTN3A3 inhibits the proliferation, migration, and invasion of ccRCC cells. Through the utilization of an immunoprecipitation assay followed by mass spectrometry, we have discovered that BTN3A3 binds directly to RPS3A. Knockdown of BTN3A3 led to increased cell proliferation, migration, and invasion. However, this effect was significantly reduced when RPS3A was simultaneously overexpressed. Previous reports have demonstrated that RPS3A positively regulates mitochondrial function and reactive oxygen species (ROS) levels. Our study has shown that overexpression of both BTN3A3 and RPS3A can increase cellular oxygen consumption rate (OCR) and ROS levels. Furthermore, we have observed that the addition of H2O2 can reverse the effects of BTN3A3 knockdown on cell proliferation and migration by increasing the cellular ROS level. ROS play a crucial role in regulating the MAPK pathway and tumor cell growth. To further explore this relationship, we examined RNA-Seq and immunoblotting data and found that BTN3A3 can negatively regulate the degree of activation of the MAPK signaling pathway. This finding suggests that the BTN3A3/RPS3A complex may regulate ccRCC progression by modulating MAPK pathways. Therefore, BTN3A3 could serve as both a prognostic marker and a potential therapeutic target for ccRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Linhagem Celular Tumoral , Invasividade Neoplásica/genética , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica
12.
Mil Med Res ; 10(1): 22, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37189155

RESUMO

Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients' anatomy. However, the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians. Moreover, some potentially useful quantitative information in medical images, especially that which is not visible to the naked eye, is often ignored during clinical practice. In contrast, radiomics performs high-throughput feature extraction from medical images, which enables quantitative analysis of medical images and prediction of various clinical endpoints. Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis, demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine. However, radiomics remains in a developmental phase as numerous technical challenges have yet to be solved, especially in feature engineering and statistical modeling. In this review, we introduce the current utility of radiomics by summarizing research on its application in the diagnosis, prognosis, and prediction of treatment responses in patients with cancer. We focus on machine learning approaches, for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling. Furthermore, we introduce the stability, reproducibility, and interpretability of features, and the generalizability and interpretability of models. Finally, we offer possible solutions to current challenges in radiomics research.


Assuntos
Inteligência Artificial , Neoplasias , Humanos , Reprodutibilidade dos Testes , Neoplasias/diagnóstico por imagem , Prognóstico , Aprendizado de Máquina
13.
Sci Total Environ ; 878: 163247, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37011687

RESUMO

Assessing soil quality variation during the prolonged application of mulched drip irrigation (MDI) is critical to comprehend the sustainability of arid agriculture. To investigate the dynamics of crucial soil-quality indicators caused by the long-term application of MDI, the "space instead of time" methodology was adopted, and six fields were selected to represent the primary successional sequence in Northwest China. A total of 21 vital soil attributes from 18 samples were used as soil quality indicators. Based on the soil quality index calculated from the entire datasets, it was observed that long-term MDI practice enhanced soil quality by 28.21 %-74.36 % due to improvements in soil structure (e.g., soil bulk density, three-phase ratio, and aggregates stability) and nutrients (including total carbon, organic carbon, total nitrogen, and available phosphorus). Compared to natural unirrigated soil, soil salinity in 0-200 cm depth significantly decreased by 51.34 %-92.39 % in cotton fields with increasing years of practicing MDI. In addition, long-term MDI practice restructured soil microbial communities and augmented microbial activity by 259.48 %-502.90 % relative to the natural salt-affected soil. However, soil quality stabilized after 12-14 years of MDI application due to accumulated residual plastic fragments, increased bulk density, and reduced microbial diversity. Overall, practicing long-term MDI promotes soil quality and crop yield by promoting soil microbiome structure and function and soil structure. However, long-term mono-cropping with MDI would result in soil compaction and impair microbial activity.

14.
Front Microbiol ; 14: 1064358, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36819023

RESUMO

Soil salinization and acidification seriously damage soil health and restricts the sustainable development of planting. Excessive application of chemical fertilizer and other reasons will lead to soil acidification and salinization. This study focus on acid and salinized soil, investigated the effect of phosphate-solubilizing bacteria, Aspergillus niger MJ1 combined with nitrogen-fixing bacteria Pseudomonas stutzeri DSM4166 or mutant Pseudomonas fluorescens CHA0-nif on crop quality, soil physicochemical properties, and microbial communities. A total of 5 treatments were set: regular fertilization (T1), regular fertilization with MJ1 and DSM4166 (T2), regular fertilization with MJ1 and CHA0-nif (T3), 30%-reducing fertilization with MJ1 and DSM4166 (T4), and 30%-reducing fertilization with MJ1 and CHA0-nif (T5). It was found that the soil properties (OM, HN, TN, AP, AK, and SS) and crop quality of cucumber (yield production, protein, and vitamin C) and lettuce (yield production, vitamin C, nitrate, soluble protein, and crude fiber) showed a significant response to the inoculated strains. The combination of MJ1 with DSM4166 or CHA0-nif influenced the diversity and richness of bacterial community in the lettuce-grown soil. The organismal system-, cellular process-, and metabolism-correlated bacteria and saprophytic fungi were enriched, which were speculated to mediate the response to inoculated strains. pH, OM, HN, and TN were identified to be the major factors correlated with the soil microbial community. The inoculation of MJ1 with DSM4166 and CHA0-nif could meet the requirement of lettuce and cucumber growth after reducing fertilization in acid and salinized soil, which provides a novel candidate for the eco-friendly technique to meet the carbon-neutral topic.

15.
Dis Markers ; 2023: 3560340, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36755802

RESUMO

Methods: Differentially transcription factors (DETFs) were identified from differentially expressed genes (DEGs) in GSE62232 and transcription factors. Then, they were analyzed by regulatory networks, prognostic risk model, and overall survival analyses to identify the key DETF. Combined with the regulatory networks and binding site analysis, the target mRNA of key DETF was determined, and its prognostic value in HCC was evaluated by survival, clinical characteristics analyses, and experiments. Finally, the expressions and functions of the key DETF on the DEmRNAs were investigated in HCC cells. Results: Through multiple bioinformatics analyses, ASCL1 was identified as the key DETF, and SLC6A13 was predicted to be its target mRNA with the common binding site of CCAGCAACTGGCC, both downregulated in HCC. In survival analysis, high SLC6A13 was related to better HCC prognosis, and SLC6A13 was differentially expressed in HCC patients with clinical characteristics. Furthermore, cell experiments showed the mRNA expressions of ASCL1 and SLC6A13 were both reduced in HCC, and their overexpressions suppressed the growth, invasion, and migration of HCC cells. Besides, over-ASCL1 could upregulate SLC6A13 expression in HCC cells. Conclusion: This study identifies two suppressor genes in HCC progression, ASCL1 and SLC6A13, and the key transcription factor ASCL1 suppresses HCC progression by targeting SLC6A13 mRNA. They are both potential treatment targets and prognostic biomarkers for HCC patients, which provides new clues for HCC research.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fatores de Transcrição/genética , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Biologia Computacional , Prognóstico , RNA Mensageiro/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
16.
Org Biomol Chem ; 21(6): 1270-1274, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36637117

RESUMO

Based on aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT) mechanisms, a fluorescent probe SWJT-12 for the detection of ClO- was designed by using the CN bond as a reactive group. This synthesized probe can react with ClO- in a high aqueous phase, and it shows a large Stokes shift (144 nm) and low biological toxicity. Its limit of detection was calculated to be 0.28 µM. Furthermore, SWJT-12 was successfully used for ratiometric imaging of the exogenous hypochlorite anion in living cells.


Assuntos
Ácido Hipocloroso , Imagem Óptica , Humanos , Células HeLa , Microscopia de Fluorescência , Corantes Fluorescentes/química
17.
Bioorg Chem ; 131: 106329, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36565674

RESUMO

A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.


Assuntos
Antineoplásicos , Diterpenos , Euphorbia , Humanos , Linhagem Celular Tumoral , Diterpenos/síntese química , Diterpenos/farmacologia , Euphorbia/química , Células Hep G2 , Simulação de Acoplamento Molecular , Estrutura Molecular , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia
18.
Sci Total Environ ; 863: 161029, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36549533

RESUMO

In drylands, soil microorganisms play a vital role in restoring degraded soils, and soil microbiota is significantly affected by human activities and climate events, such as seasonal freezing and thawing. However, the response of soil microbes to freezing and thawing, as well as their properties in drylands agroecosystems, remains unknown. This study investigated the effects of seasonal freezing and thawing on soil fungal and bacterial communities, multifunctionality, and soil microbial quality in a dryland agroecosystem. It has been observed that seasonal freezing and thawing promoted nutrient releases such as total carbon and available phosphorus. After thawing, soil catalase and cellulase activities increased while acid phosphatase and urease activities and total nitrogen content at topsoil decreased. Soil microbial biomass carbon content at 0-40 cm depth was significantly reduced by 94.77 %. Importantly, freezing and thawing considerably shifted the composition of fungal groups, while the soil bacterial community exhibited more stress tolerance to freezing-thawing. Compared to pre-freezing, the relative abundance of dominant fungal phyla such as Basidiomycota and Mortierellomycota decreased. At the same time, Ascomycota increased after thawing, and the relative abundance of pathogenic fungus also increased. For dominant bacteria phylum, freezing and thawing increased the relative abundance of Proteobacteria and Gemmatimonadetes while Micrococcaceae declined. Freezing and thawing significantly increased bacterial diversity and evenness by 4.94 % and 4.19 %, respectively, but decreased fungal richness and diversity by 23.49 % and 14.91 %, respectively. The minimum and total data sets were used to evaluate soil quality and we found that freezing and thawing significantly negatively impacted soil multifunctionality and microbial quality. In summary, this study demonstrates that the seasonal freezing-thawing has a significant negative impact on soil microbial quality and multifunctionality, and accelerates soil degeneration in dryland agroecosystem.


Assuntos
Microbiologia do Solo , Solo , Humanos , Congelamento , Bactérias , China , Carbono
19.
J Biol Chem ; 299(2): 102819, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36549648

RESUMO

Zinc (Zn) is an essential trace element; it serves as a cofactor for a great number of enzymes, transcription factors, receptors, and other proteins. Zinc is also an important signaling molecule, which can be released from intracellular stores into the cytosol or extracellular space, for example, during synaptic transmission. Amongst cellular effects of zinc is activation of Kv7 (KCNQ, M-type) voltage-gated potassium channels. Here, we investigated relationships between Kv7 channel inhibition by Ca2+/calmodulin (CaM) and zinc-mediated potentiation. We show that Zn2+ ionophore, zinc pyrithione (ZnPy), can prevent or reverse Ca2+/CaM-mediated inhibition of Kv7.2. In the presence of both Ca2+ and Zn2+, the Kv7.2 channels lose most of their voltage dependence and lock in an open state. In addition, we demonstrate that mutations that interfere with CaM binding to Kv7.2 and Kv7.3 reduced channel membrane abundance and activity, but these mutants retained zinc sensitivity. Moreover, the relative efficacy of ZnPy to activate these mutants was generally greater, compared with the WT channels. Finally, we show that zinc sensitivity was retained in Kv7.2 channels assembled with mutant CaM with all four EF hands disabled, suggesting that it is unlikely to be mediated by CaM. Taken together, our findings indicate that zinc is a potent Kv7 stabilizer, which may protect these channels from physiological inhibitory effects of neurotransmitters and neuromodulators, protecting neurons from overactivity.


Assuntos
Cálcio , Calmodulina , Espaço Intracelular , Canais de Potássio KCNQ , Zinco , Sinalização do Cálcio , Calmodulina/metabolismo , Canais de Potássio KCNQ/antagonistas & inibidores , Canais de Potássio KCNQ/química , Canais de Potássio KCNQ/genética , Canais de Potássio KCNQ/metabolismo , Mutação , Ligação Proteica/genética , Zinco/farmacologia , Zinco/metabolismo , Espaço Intracelular/metabolismo , Cálcio/metabolismo , Canal de Potássio KCNQ2/antagonistas & inibidores , Canal de Potássio KCNQ2/química , Canal de Potássio KCNQ2/genética , Canal de Potássio KCNQ2/metabolismo , Canal de Potássio KCNQ3/antagonistas & inibidores , Canal de Potássio KCNQ3/química , Canal de Potássio KCNQ3/genética , Canal de Potássio KCNQ3/metabolismo
20.
Chinese Traditional Patent Medicine ; (12): 3914-3921, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1028705

RESUMO

AIM To observe the protective effects of Qigu Capsule-medicated serum on C2C12 myotube cell atrophy induced by dexamethasone.METHODS The Qigu Capsule-medicated serum was prepared.C2C12 cells cultured in vitro were divided into the normal control group,the dexamethasone group,the 10%blank serum group and the 10%Qigu Capsule-medicated serum group for 48 h,corresponding drug treatment,followed by 24 h culture with 10 μmol/L dexamethasone except the control group,and had cell viability detection by CCK-8 method.With their myotube cells intervened accordingly by the aforementioned regime following 6-7 days differentiation with 2%horse serum induction,the C2C12 cells had their myotube cells diameter measured;and the expressions of proteins related to MyHC,MuRF-1,Atrogin-1 and PI3K/Akt signaling pathway detected by Western blot.The impact of PI3K inhibitor LY294002 on the diameter of myotube cells and the expression of MuRF-1,Atorgin-1 and PI3K/Akt signaling pathway related proteins were detected as well.RESULTS Compared with the normal control group,the dexamethasone group and the blank serum group were observed with decreased viability of C2C12 cells(P<0.01),decreased diameter of myotube cells(P<0.01),increased protein expressions of MuRF-1 and Atrogin-1(P<0.01),and decreased expression of MyHC protein and phosphorylation levels of PI3K,Akt,mTOR and FoxO3a(P<0.01).Compared with the dexamethasone group,the Qigu Capsule-medicated serum group showed increased viability of C2C12 cells(P<0.01);increased diameter of myotube cells(P<0.01);decreased protein expressions of MuRF-1 and Atrogin-1(P<0.01);and increased expression of MyHC protein and phosphorylation levels of PI3K,Akt,mTOR and FoxO3a(P<0.05,P<0.01).The intervention of LY294002 upon the Qigu Capsule-medicated serum group offset the anti-muscular tube atrophy effect(P<0.01),increased the protein expressions of MuRF-1 and Atorgin-1(P<0.01),and decreased the phosphorylation levels of PI3K,Akt,mTOR and FoxO3a(P<0.05,P<0.01).CONCLUSION The Qigu Capsule-medicated serum can alleviate the atrophy of C2C12 myotubes induced by dexamethasone,and its mechanism may be related to the activation of PI3K/Akt signaling pathway.

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