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1.
Toxicol Mech Methods ; : 1-11, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36097686

RESUMO

With the extensive application of titanium dioxide nanoparticles (TiO2 NPs), their impacts on calcium homeostasis have aroused extensive attention from scholars. However, there are still some controversies in relevant reports. Therefore, a systematic review was performed followed by a meta-analysis to explore whether TiO2 NPs could induce the imbalance in calcium homeostasis in vivo and in vitro through Revman5.4 and Stata15.0 in this research. Fourteen studies were included through detailed database retrieval and literature screening. Results indicated that the calcium levels were significantly increased and the activity of Ca2+-ATPase was significantly decreased by TiO2 NPs in vivo and in vitro. Subgroup analysis of the studies in vivo showed that TiO2 NPs exposure caused a significant increase in calcium levels in rats, exposure to large-sized TiO2 NPs (>10 nm) and long-term (>30 days) exposure could significantly increase calcium levels, and the activity of Ca2+-ATPase showed a concentration-dependent downward trend. Subgroup analysis of the studies in vitro revealed that intracellular calcium levels increased significantly in animal cells, exposure to small-sized TiO2 NPs (≤10 nm) and high concentration (>10 µg/mL) exposure could induce a significant increase in Ca2+ concentration, and the activity of Ca2+-ATPase also showed a concentration-dependent downward trend. This research showed that the physicochemical properties of TiO2 NPs and the experimental scheme could affect calcium homeostasis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36118100

RESUMO

Background: The gut-cardiac axis theory provides new insights into the complex mechanisms of cardiac hypertrophy and provides new therapeutic targets. Cardiac hypertrophy is a risk factor for heart failure. Shengmaiyin (SMY) is a traditional Chinese medicine formula with clear effects in the treatment and prevention of cardiac hypertrophy, but the mechanism by which it improves cardiac hypertrophy is still unclear. Therefore, this study aimed to investigate the protective effect and mechanism of SMY on isoproterenol (ISO)-induced myocardial hypertrophy in rats. Methods: First, various pharmacodynamic methods were used to evaluate the therapeutic effect of SMY on ISO-induced myocardial hypertrophy in rats. Then, 16S rDNA amplicon sequencing technology was used to study the effect of SMY on the intestinal flora of rats with myocardial hypertrophy. Finally, the mechanism underlying the effect of SMY on cardiac hypertrophy was predicted by bioinformatics network analysis and verified by Western blotting. Results: SMY increased ejection fraction (EF%) and left ventricular fractional shortening (FS%), ameliorated myocardial cell injury and fibrosis, regulated blood lipids and energy metabolism, and decreased cardiac hypertrophy marker gene expression. The gut microbiota of ISO-induced myocardial hypertrophy rats were significantly changed, while SMY effectively ameliorated the dysbiosis of the intestinal flora in rats with myocardial hypertrophy, especially Prevotella 9, Lactobacillus, and Clostridium. Mechanistic studies have shown that the anticardiac hypertrophy effect of SMY is related to the inhibition of the expression of HIF1α/PPAR signalling pathway-related proteins. Conclusion: SMY significantly improves cardiac function, relieves myocardial cell fibrosis and necrosis, resists cardiac hypertrophy, improves blood lipid metabolism and energy metabolism, regulates intestinal microbial disturbance, and protects the heart.

3.
Huan Jing Ke Xue ; 43(9): 4674-4683, 2022 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-36096608

RESUMO

Atmospheric nitrogen deposition has a crucial impact on the structure and function of soil microorganisms of wetland ecosystems. Therefore, carrying out a study on the effects of soil carbon metabolism capacity has a great significance for the protection and utilization of wetland ecosystems. In this study, the effects of simulated nitrogen deposition on the carbon metabolic capacity of soil microorganisms in Calamagrostis angustifolia wetland for five consecutive years was investigated using Biolog-Eco technology. The results showed:① soil water content (SMC), pH, nitrate nitrogen (NO3-), ammonium nitrogen (NH4+), dissolved organic carbon (DOC), and total nitrogen (TN) contents were significantly different (P<0.05) under different nitrogen deposition conditions. ② The average well color development (AWCD) values of soil microorganisms within different N depositions were in the order of CK (control)>HN (high nitrogen treatment)>LN (low nitrogen treatment). LN significantly reduced the Shannon diversity index of soil microorganisms, and HN significantly reduced the Pielou index of soil microorganisms (P<0.05). ③ LN significantly inhibited the intensity of the utilization of carbohydrates, alcohols, amines, and acids by soil microorganisms (P<0.05); HN significantly promoted the utilization of esters by microorganisms, but HN caused soil microorganisms to inhibit the carbon sources of carbohydrates, amines, and acids (P<0.05). ④ Redundancy analysis showed that NH4+, DOC, and pH were the main environmental factors affecting the functional diversity of soil microbial communities in Calamagrostis angustifolia wetland in the Sanjiang Plain. Long-term nitrogen deposition will lead to the reduction in soil microbial functional diversity; the microbial activity related to the utilization of carbon source substrates is also significantly reduced, and the ability of microorganisms to utilize a single carbon source substrate also changes.


Assuntos
Nitrogênio , Solo , Aminas/metabolismo , Carboidratos , Carbono/química , Ecossistema , Nitrogênio/análise , Poaceae , Solo/química , Microbiologia do Solo , Áreas Alagadas
4.
Math Biosci Eng ; 19(11): 11717-11734, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36124610

RESUMO

In this paper, synchronization of fractional-order memristive recurrent neural networks via aperiodically intermittent control is investigated. Considering the special properties of memristor neural network, differential inclusion theory is introduced. Similar to the aperiodically strategy of integer order, aperiodically intermittent control strategy of fractional order is proposed. Under the framework of Fillipov's solution, based on the intermittent strategy of fractional order systems and the properties Mittag-Leffler, sufficient criteria of aperiodically intermittent strategy are obtained by constructing appropriate Lyapunov functional. Some comparisons are given to demonstrate the advantages of aperiodically strategy. A simulation example is given to illustrate the derived conclusions.


Assuntos
Algoritmos , Redes Neurais de Computação
5.
Database (Oxford) ; 20222022 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-35962559

RESUMO

Large volumes of publications are being produced in biomedical sciences nowadays with ever-increasing speed. To deal with the large amount of unstructured text data, effective natural language processing (NLP) methods need to be developed for various tasks such as document classification and information extraction. BioCreative Challenge was established to evaluate the effectiveness of information extraction methods in biomedical domain and facilitate their development as a community-wide effort. In this paper, we summarize our work and what we have learned from the latest round, BioCreative Challenge VII, where we participated in all five tracks. Overall, we found three key components for achieving high performance across a variety of NLP tasks: (1) pre-trained NLP models; (2) data augmentation strategies and (3) ensemble modelling. These three strategies need to be tailored towards the specific tasks at hands to achieve high-performing baseline models, which are usually good enough for practical applications. When further combined with task-specific methods, additional improvements (usually rather small) can be achieved, which might be critical for winning competitions. Database URL: https://doi.org/10.1093/database/baac066.


Assuntos
Mineração de Dados , Processamento de Linguagem Natural , Mineração de Dados/métodos , Bases de Dados Factuais , Aprendizado de Máquina
6.
Ecotoxicol Environ Saf ; 242: 113938, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926408

RESUMO

Salinity is one of the most common factors affecting alfalfa (Medicago sativa L.), and NaCl is one of the main factors of salinity stress which can cause heavy losses in agricultural production in the world. The application of exogenous melatonin (MT) plays a major role in numerous plants against various stress environments. The effects of exogenous MT on the NaCl tolerance of alfalfa treated with the control, 100 µmol L-1 MT, 150 mmol L-1 NaCl, or 150 mmol L-1 NaCl+ 100 µmol L-1 MT were investigated. The results showed that MT increased growth parameters, inhibited chlorophyll degradation and promoted photosynthetic gas exchange parameters (photosynthetic rate, conductance to H2O, and transpiration rate) and stomatal opening under NaCl stress. Osmotic regulation substances such as soluble sugar, proline and glycine betaine were the highest in the NaCl treatment and the second in the NaCl+MT treatment. Nitrogen, phosphorus, potassium, calcium and magnesium were reduced and sodium was increased by NaCl, whereas these levels were reversed by the NaCl+MT treatment. MT inhibited cell membrane imperfection, lipid peroxidation and reactive oxygen species (ROS) accumulation caused by NaCl stress. MT up-regulated the gene expression and activity of antioxidant enzymes and increased the content of antioxidant non-enzyme substances to scavenge excessive ROS in NaCl-treated plants. In addition, all indicators interacted with each other to a certain extent and could be grouped according to the relative values. All variables were divided into PC 1 (89.2 %) and PC 2 (4 %). They were clustered into two categories with opposite effects, and most of them were significant variables. Hence, these findings reveal that exogenous MT alleviates the inhibitory effects of NaCl stress on photosynthesis, stomata opening, osmotic adjustment, ion balance and redox homeostasis, enhancing tolerance and growth of alfalfa. Furthermore, it suggests that MT could be implemented to improve the NaCl tolerance of alfalfa.


Assuntos
Medicago sativa , Melatonina , Antioxidantes/metabolismo , Medicago sativa/metabolismo , Melatonina/metabolismo , Melatonina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Cloreto de Sódio/metabolismo , Cloreto de Sódio/toxicidade
7.
Clin Transl Oncol ; 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35962917

RESUMO

PURPOSE: To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. METHODS: According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan-Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. RESULTS: A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41 months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). CONCLUSIONS: For patients aged 50 years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups.

8.
Eur J Pharmacol ; 931: 175215, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35987258

RESUMO

Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a significant cause of blindness. As one of the crucial factors in the pathogenesis of DR, oxidative stress provides new insights for the treatment of DR. Tert-butylhydroquinone (TBHQ), an efficient phenolic antioxidant, has been proved to inhibit diabetic retina injury. However, the mechanism of TBHQ for DR treatment is still unclear. The present study was designed to investigate the potential mechanism of TBHQ for treating DR. Firstly, the potential targets of TBHQ and DR were selected to construct protein-protein interaction network, which was applied to illustrate the potential mechanism of TBHQ against DR. Combined with transcriptomics and molecular simulation, the potential mechanisms were systematically verified. The results showed that TBHQ inhibited retinal microvascular injury by regulating oxidative stress, inflammation, cell proliferation-death regulation, and vascular system development. The mechanisms of these activities were associated with hypoxia-inducible factor-1 (HIF-1), nuclear factor-erythroid 2 related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), forkhead box O (FoxO), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), and rhoptry-associated protein1 (Rap1) signaling pathways and their related targets nitric oxide synthase 3 (NOS3), mitogen-activated protein kinase 8 (MAPK8), prostaglandin-endoperoxide synthase 2 (PTGS2), and heme oxygenase 1 (HMOX1). In conclusion, a systematic perspective for the mechanism of TBHQ against DR was revealed by present study which lays a foundation for the application of TBHQ in treating DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Humanos , Hidroquinonas , Fator 2 Relacionado a NF-E2/metabolismo , Farmacologia em Rede , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Transcriptoma , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Ann Transl Med ; 10(15): 818, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36035003

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) has been linked to gallstone disease (GSD) in observational studies; however, the relationships between certain lipid profiles and GSD remain unclear. Methods: We adopted a two-sample Mendelian randomization (MR) framework by applying different statistical methods to assess causalities between lipid profiles and GSD. We identified single-nucleotide polymorphisms (SNPs) for blood lipids and NAFLD from separate previous genome-wide association studies (GWASs). Results: We retrieved GSD SNPs attributed to 10,520 cases and 361,194 controls and validated our estimates using GWAS summary data from UK Biobank. We also performed sex-stratified analyses. Based on the summary estimates of 41, 59, 35, and 2 SNPs for low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), triglycerides (TGs), and NAFLD, respectively, we found no evidence of a causal relationship between genetically-predicted lipid profiles and GSD. The odds ratios were 0.995 for LDLC [95% confidence interval (CI): 0.994-0.998] per 0.98 mmol/L, 0.999 for HDLC (95% CI: 0.996-1.003) per 0.41 mmol/L, 0.997 for TGs (95% CI: 0.994-1.001) per 1 mmol/L, and 0.993 for NAFLD (95% CI: 0.984-1.003). No evidence of associations between lipid profile s and GSD in validation MR analyses or the sex-stratification analyses was noted. Conclusions: Genetically predicted hyperlipidemia or NAFLD is not causally associated with GSD.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35805655

RESUMO

The "Multi-Threat Medical Countermeasure (MTMC)" strategy was proposed to develop a single drug with therapeutic efficacy against multiple pathologies or broad-spectrum protection against various toxins with common biochemical signals, molecular mediators, or cellular processes. This study demonstrated that cytotoxicity, expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) mRNA, and intracellular calcium influx were increased in A549 cells exposed to amide herbicides (AHs), in which the order of cytotoxicity was metolachlor > acetochlor > propisochlor > alachlor > butachlor > propanil > pretilachlor, based on IC50 values of 430, 524, 564, 565, 619, 831, and 2333 µM, respectively. Inhibition/knockout of TRPA1 efficiently protected against cytotoxicity, decreased TRPA1 mRNA expression, and reduced calcium influx. The results suggested that the TRPA1 channel could be a key common target for AHs poisoning. The order of TRPA1 affinity for AHs was propanil > pretilachlor > metolachlor > (propiso/ala/aceto/butachlor), based on KD values of 16.2, 309, and 364 µM, respectively. The common molecular mechanisms of TRPA1-AHs interactions were clarified, including toxicity-effector groups (benzene ring, nitrogen/oxygen-containing functional groups, halogen) and residues involved in interactions (Lys787, Leu982). This work provides valuable information for the development of TRPA1 as a promising therapeutic target for broad-spectrum antitoxins.


Assuntos
Herbicidas , Propanil , Amidas/toxicidade , Cálcio/metabolismo , Herbicidas/química , RNA Mensageiro , Canal de Cátion TRPA1/genética , Canal de Cátion TRPA1/metabolismo
11.
Mol Brain ; 15(1): 53, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701839

RESUMO

Dysfunction of striatal dopaminergic circuits has been implicated in motor impairment and Parkinson's disease (PD)-related circadian perturbations that may represent an early prodromal marker of PD. Cyclin-dependent kinase 5 (CDK5) negatively regulates dopamine signaling in the striatum, suggesting a critical role of CDK5 in circadian and sleep disorders. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing to produce mice with a dorsal striatum (DS)-specific knockdown (KD) of the Cdk5 gene (referred to as DS-CDK5-KD mice) and investigate its role in vivo. DS-CDK5-KD mice exhibited deficits in locomotor activity and disturbances in activity/rest behavior. Additionally, Golgi staining of neurons in the DS revealed that CDK5 deletion reduced dendrite length and the number of functional synapses, which was confirmed by significant downregulation of MAP2, PSD-95, and synapsin I. Correlated with this, DS-CDK5-KD mice displayed reduced phosphorylation of Tau at Thr181. Furthermore, whole-cell patch-clamp recordings of green fluorescent protein-tagged neurons in the striatum of DS-CDK5-KD mice revealed a decreased frequency of spontaneous inhibitory postsynaptic currents and altered excitatory/inhibitory synaptic balance. Notably, anterograde labeling showed that CDK5 KD in the DS disrupted long-range projections to the secondary motor cortex, dorsal and ventral thalamic nuclei, and basolateral amygdala, which are involved in the regulation of motor and circadian rhythms in the brain. These findings support a critical role of CDK5 in the DS in maintaining the striatal neural circuitry underlying motor functions and activity/rest associated with circadian rhythms that are perturbed in neurodegenerative disorders.


Assuntos
Ritmo Circadiano , Quinase 5 Dependente de Ciclina , Animais , Corpo Estriado/metabolismo , Quinase 5 Dependente de Ciclina/metabolismo , Dopamina , Regulação para Baixo , Camundongos , Sinapses/metabolismo
12.
Eur Radiol ; 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35748899

RESUMO

OBJECTIVES: To investigate whether deep learning reconstruction (DLR) could keep image quality and reduce radiation dose in interstitial lung disease (ILD) patients compared with HRCT reconstructed with hybrid iterative reconstruction (hybrid-IR). METHODS: Seventy ILD patients were prospectively enrolled and underwent HRCT (120 kVp, automatic tube current) and LDCT (120 kVp, 30 mAs) scans. HRCT images were reconstructed with hybrid-IR (Adaptive Iterative Dose Reduction 3-Dimensional [AIDR3D], standard-setting); LDCT images were reconstructed with DLR (Advanced Intelligence Clear-IQ Engine [AiCE], lung/bone, mild/standard/strong setting). Image noise, streak artifact, overall image quality, and visualization of normal and abnormal features of ILD were evaluated. RESULTS: The mean radiation dose of LDCT was 38% of HRCT. Objective image noise of reconstructed LDCT images was 33.6 to 111.3% of HRCT, and signal-to-noise ratio (SNR) was 0.9 to 3.1 times of the latter (p < 0.001). LDCT-AiCE was not significantly different from or even better than HRCT in overall image quality and visualization of normal lung structures. LDCT-AiCE (lung, mild/standard/strong) showed progressively better recognition of ground glass opacity than HRCT-AIDR3D (p < 0.05, p < 0.01, p < 0.001), and LDCT-AiCE (lung, mild/standard/strong; bone, mild) was superior to HRCT-AIDR3D in visualization of architectural distortion (p < 0.01, p < 0.01, p < 0.01; p < 0.05). LDCT-AiCE (bone, strong) was better than HRCT-AIDR3D in the assessment of bronchiectasis and/or bronchiolectasis (p < 0.05). LDCT-AiCE (bone, mild/standard/strong) was significantly better at the visualization of honeycombing than HRCT-AIDR3D (p < 0.05, p < 0.05, p < 0.01). CONCLUSION: Deep learning reconstruction could effectively reduce radiation dose and keep image quality in ILD patients compared to HRCT with hybrid-IR. KEY POINTS: • Deep learning reconstruction was a novel image reconstruction algorithm based on deep convolutional neural networks. It was applied in chest CT studies and received auspicious results. • HRCT plays an essential role in the whole process of diagnosis, treatment efficacy evaluation, and follow-ups for interstitial lung disease patients. However, cumulative radiation exposure could increase the risks of cancer. • Deep learning reconstruction method could effectively reduce the radiation dose and keep the image quality compared with HRCT reconstructed with hybrid iterative reconstruction in patients with interstitial lung disease.

13.
Brain Res ; 1790: 147987, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35724762

RESUMO

Acute hypobaric hypoxia (AHH) exposure causes altitude mountain sickness (AMS) and life-threatening high altitude cerebral edema (HACE). Despite decades of research, the role of cerebral blood flow (CBF) changes in the pathophysiology of severe AMS remains unclear. The current study evaluated spatiotemporal responses of CBF associated with HACE in mice during the early stages of ascent to high altitudes. First, mice were exposed to AHH to test their tolerance to increasing altitudes (3000-8000 m). Because of its significant influence on both locomotor activity and rotarod behavior tests in mice, further observations were initiated at an altitude of 6000 m to investigate the specific pathophysiology of AMS. Compared with controls, laser speckle contrast imaging (LSCI) revealed a significant decrease in CBF during the early stage (0.5-24 h) at an altitude of 6000 m that was accompanied by a significant increase in brain water content (BWC). Moreover, observations of brain lipid oxidative damage and oxidative stress during the early stage of AHH exposure revealed DNA and cellular damage in cortical and hippocampal regions. Transcriptome profiling of the hippocampus revealed upregulation of forkhead box transcription factors. Similarly, western blot assays revealed upregulation of FOXO1a, FOXO3a, caspase-3 and Bax, and downregulation of Bcl-2, indicating a temporal influence of AHH on mitochondrial function and neuronal apoptosis. Thus, we found that the pathophysiology of HACE occurred with dynamic CBF changes, which triggered oxidative stress and neuronal damage in the mouse brain after AHH exposure. Our findings provide potential strategies for treatment of AHH in the future.


Assuntos
Doença da Altitude , Edema Encefálico , Altitude , Animais , Circulação Cerebrovascular/fisiologia , Hipóxia , Camundongos
14.
J Environ Pathol Toxicol Oncol ; 41(2): 47-59, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35695651

RESUMO

Glioma is a common type of malignancy in the central nervous system. The pathogenesis of glioma is complex and the underlying mechanisms remain largely unknown. In our study, exosomes were exacted from patient samples, and the isolated exosomes were confirmed by transmission electron microscope. The expression of circRNA_104948, miR-29b-3p and DNMT3B were determined using RT-qPCR. Proliferative activity of cell was examined using CCK-8 assay. Cell apoptotic rate was evaluated by flow cytometry. The expression levels of proliferation or apop-tosis markers were determined using western blotting. Our data suggested that circRNA_104948 was upregulated in plasma exosomes/tissue samples of glioma patients and glioma cell lines. Furthermore, cell proliferation was enhanced and apoptosis was suppressed in normal astrocytes treated with exosomal circRNA_104948, and the effects were reversed by sh-circRNA_104948. In addition, miR-29b-3p is a novel target of circRNA_104948, and DNMT3B is a putative downstream molecule of miR-29b-3p. circRNA_104948 could regulate the proliferation/apoptosis of astrocytes through miR-29b-3p/DNMT3B/MTSS1 signaling, and the biological behavior changes induced by glioma-Exo were reversed by miR-29b-3p mimics; upregulated cell growth caused by miR-29b-3p inhibitors was abrogated by the knockdown of DNMT3B; the effects induced by miR-29b-3p mimics were abolished by the overexpression of DNMT3B. Our findings revealed the important roles of circRNA_104948 on the development of glioma, and circRNA_104948/miR-29b-3p/MTSS1/DNMT3B pathway may be a potential candidate for the target therapy of glioma patients.


Assuntos
Glioma , MicroRNAs , Apoptose , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases/metabolismo , Glioma/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas de Neoplasias , RNA Circular/genética , Transdução de Sinais
15.
Chin J Integr Med ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508859

RESUMO

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.

16.
Brain Res ; 1789: 147950, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35618015

RESUMO

Bombesin (BN) is an itch-specific mediator that causes intense itch-scratching activity in mammals. Although most examinations of BN-induced itch processing have focused on the spinal cord, the involvement of central nervous system mechanisms remains unclear. Here, we investigated how relationships among hypothalamic regions regulate BN-mediated itch-scratch processes. We found that intracerebroventricular (i.c.v.) administration of BN (0.04-4 µg) elicited intense itch scratching in mice, whereas BN (0.4-400 µg) administered via intravenous tail injection failed to evoke a scratching response. Additionally, nalfurafine had no significant effects on BN-induced scratching behavior, indicating that central modulation of BN is distinct from histamine-mediated histaminergic itch and chloroquine-mediated non-histaminergic itch signaling pathways. We labeled BN with a fluorescent tag, 7-nitrobenz-2-oxa-1 (NBD), and traced its fluorescence in the hypothalamus for 30 min following i.c.v. NBD-BN administration. Accordingly, we confirmed that i.c.v. administration of BN enhanced c-Fos expression in the dorsal medial nucleus of the hypothalamus, where neuromedin B receptors and gastrin-releasing peptide receptors are highly expressed. Interestingly, in situ injection of BN into the hypothalamus immediately and robustly induced itch-scratching behavior. Moreover, gene transcripts and western blot assay revealed that BN receptor-dependent PKA/CREB signaling was upregulated in the hypothalamus after i.c.v. administration of BN. Consistently, pretreatment with a PKA inhibitor, Rp-cAMP, significantly reduced BN-induced scratching behavior. Our results indicate that the dorsal medial nucleus of the hypothalamus may be a key nucleus in mediating BN-mediated itch and hypothalamic PKA/CREB signaling is involved in regulating BN-mediated itch.


Assuntos
Bombesina , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Proteínas Quinases Dependentes de AMP Cíclico , Hipotálamo , Animais , Bombesina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Camundongos , Prurido/induzido quimicamente , Prurido/metabolismo , Receptores da Bombesina/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Front Pharmacol ; 13: 863451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450040

RESUMO

Hypoxic environments at high altitudes influence the long-term non-altitude health of residents, by inducing changes in metabolism and the mitochondria, severe lung injury, and endangering life. This study was aimed to determine whether meldonium can ameliorate hypoxia-induced lung injury and investigate its possible molecular mechanisms. We used Swiss mice and exposed type Ⅱ alveolar epithelial cell to hypobaric hypoxic conditions to induce lung injury and found that meldonium has significant preventive effect, which was associated with the regulation of glycolysis. We found using human proteome microarrays assay, molecular docking, immunofluorescence and pull-down assay that the target protein of meldonium is a platelet-type phosphofructokinase (PFKP), which is a rate-limiting enzyme of glycolysis. Also, meldonium promotes the transfer of nuclear factor erythroid 2-related factor 2 (Nrf2) from the cytoplasm to the nucleus, which mitigates oxidative stress and mitochondrial damage under hypoxic condition. Mechanistically, meldonium ameliorates lung injury by targeting PFKP to regulate glycolysis, which promotes Nrf2 translocation from the cytoplasm to the nucleus to alleviate oxidative stress and mitochondrial damage under hypoxic condition. Our study provides a novel potential prevention and treatment strategy against hypoxia-induced lung injury.

18.
Microorganisms ; 10(4)2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35456878

RESUMO

This study assessed the effects of Betula dahurica (BD), Betula platyphylla (BP), Larix gmelinii (LG), Quercus mongolica (QM), and a mixed conifer-broadleaf forest composed of LG and QM (LGQM) on the soil physicochemical parameters and community structure of fungi in the Zhongyangzhan Black-billed Capercaillie Nature Reserve. Fungal community structures were characterized via ITS rRNA sequencing. The effects of soil parameters on the community structure of soil fungi were assessed by Pearson correlation analysis and redundancy analysis (RDA). LGQM exhibited lower C/N, available nitrogen (AN), total phosphorus (TP), and available phosphorus (AP) compared with the QM broadleaf forest. The fungal Shannon and Simpson diversity indices were highest in BP, whereas LG exhibited the highest ACE index. The Basidiomycota, Ascomycota, Mortierellomycota, and Mucoromycota fungal phyla were dominant across all vegetation types. Each of the different vegetation types studied herein exhibited a unique fungal community structure. The RDA results indicated that fungal community structures were primarily shaped by the total N, available N, and available P of soil. Our findings thus indicated that forests restored with different species of trees may exhibit variations in soil quality and characteristics despite sharing the same climate. Furthermore, broadleaved and coniferous forests exhibited a unique fungal community diversity and composition.

19.
Biomaterials ; 284: 121486, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35447404

RESUMO

As nanotherapeutics, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are considered a potent alternative for whole-cell therapy and are gradually entering the clinical field of liver diseases. In this study, neutrophil extracellular traps (NETs) formation in liver tissue was verified as a critical factor for liver ischaemia-reperfusion injury (IRI) in both clinical samples and animal models. Human umbilical cord-derived MSC-EVs (hUC-MSC-EVs) might function to reduce the NETs formation and subsequently improve liver IRI. Mechanistically, we showed that hUC-MSC-EVs contain functional mitochondria that are transferred to intrahepatic neutrophils. This effect triggers mitochondrial fusion and subsequently restores the mitochondrial status and functions in neutrophils to reduce NETs formation. Collectively, our findings suggest that MSC-EVs exert a nanotherapeutic effect on inhibiting local NETs formation by transferring functional mitochondria to intrahepatic neutrophils and repairing their mitochondrial function, which highlights the therapeutic value of hUC-MSC-EVs for liver IRI.


Assuntos
Armadilhas Extracelulares , Vesículas Extracelulares , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Animais , Vesículas Extracelulares/metabolismo , Fígado , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/terapia
20.
Front Aging Neurosci ; 14: 807082, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431897

RESUMO

Background: Frailty is considered a major public health challenge of the 21st century, characterized by the decline of multiform body functions. Physical activity may be the most effective intervention to delay frailty. This study aims to verify the effect of remotely supervised physical activity on health profile in community-dwelling frail older adults. Design: This is a multicenter, three-blind, two-arm, and cohort randomized controlled study. Methods: The intelligent exercise rehabilitation management system (IERMS) is an integrated digital platform that involves evaluation, guidance, monitoring, and feedback. A total of 120 participants aged ≥ 65 years and diagnosed as frailty on the FRAIL scale will be recruited and randomly divided into two groups. Group 1 will receive a 12-week IERMS-based intervention, and Group 2 will receive the usual care. Data will be collected at baseline, 12 and 24 weeks. The primary outcome is the physical function, and secondary outcomes include gait parameters, psychology, and cognition measurements. Analyses will be performed using DSS statistics, version 25. P < 0.05 will be considered statistically significant. Conclusion: We believe that intervention plays a positive role in delaying the frailty. If our program is effective, we will provide a viable means to promote healthy aging in primary healthcare. Trial registration number: ChiCTR2100052286; Pre-results.

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