RESUMO
Encoding and recalling spoken instructions is subject to working memory capacity limits. Previous research suggests action-based encoding facilitates instruction recall, but has not directly compared benefits across different types of action-based techniques. The current study addressed this in two experiments with young adults. In Experiment 1, participants listened to instructional sequences containing four action-object pairs, and encoded these instructions using either a motor imagery or verbal rehearsal technique, followed by recall via oral repetition or enactment. Memory for instructions was better when participants used a motor imagery technique during encoding, and when recalling the instructions by enactment. The advantage of using a motor imagery technique was present in both verbal and enacted recall. In Experiment 2, participants encoded spoken instructions whilst implementing one of four techniques (verbal rehearsal, motor imagery, observation of others' actions or self-enactment), and then recalled the instructions by oral repetition or enactment. For both verbal and enacted recall, memory for instructions was least accurate in the rehearsal condition, while the other encoding conditions did not differ from each other. These novel findings indicate similar benefits of imagining, observation and execution of actions in encoding spoken instructions, and enrich current understanding of action-based benefits in working memory.
Assuntos
Aprendizagem , Memória de Curto Prazo , Adulto Jovem , Humanos , Rememoração Mental , Imagens, PsicoterapiaRESUMO
This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.
Assuntos
Lesões Pré-Cancerosas , Neoplasias Gástricas , Ratos , Animais , Neoplasias Gástricas/genética , Ratos Sprague-Dawley , Mitofagia , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Proliferação de CélulasRESUMO
Objective: Baolier Capsule (BLEC) is a Traditional Mongolian Medicine comprising fifteen herbs. This study aims to illustrate the synergistic mechanism of BLEC in the treatment of Coronary Artery Disease (CAD) by using network pharmacology method, molecular docking and experimental validation. Methods: Searching and screening the active ingredients of different herbs in BLEC and target genes related to CAD in multiple databases. Subsequently, Protein-Protein Interactions Network (PPI-Net), gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment were used to identify the key targets. AutoDock was used to verify the binding ability between the active ingredient and key target through molecular docking. Reverse Transcription-Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) was used to verify the effect of active ingredient of BLEC on the key target gene. Finally, effect of BLEC on the degree of blood lipids and atherosclerosis was validated by animal experiment. Results: There are 144 active components and 80 CAD-related targets that are identified in BLEC in the treatment of CAD. What is more, 8 core genes were obtained by clustering and topological analysis of PPI-Net. Further, GO and KEGG analysis showed that fluid shear stress and atherosclerosis are the key pathways for BLEC to treat CAD. These results were validated by molecular docking method. In vitro, active compounds of BLEC (Quercetin, luteolin, kaempferol, naringenin, tanshinone IIA, ß-carotene, 7-O-methylisomucronulatol, piperine, isorhamnetin and Xyloidone) can inhibit 8 core gene (AKT1, EGFR, FOS, MAPK1, MAPK14, STAT3, TP53 and VEGFA) expression. Moreover, BLEC not only improve blood lipid levels but also inhibit the development of atherosclerosis in ApoE-knockout mice. Conclusion: Our research first revealed the basic pharmacological effects and related mechanisms of in the treatment of CAD. The predicted results provide some theoretical support for BLEC or its important active ingredients to treat CAD.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Medicamentos de Ervas Chinesas , Animais , Camundongos , Simulação de Acoplamento Molecular , Medicina Tradicional da Mongólia , Farmacologia em RedeRESUMO
OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.
Assuntos
Medicamentos de Ervas Chinesas , Refluxo Gastroesofágico , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Farmacologia em Rede , Mineração de Dados , Refluxo Gastroesofágico/tratamento farmacológicoRESUMO
BACKGROUND: Disturbance of the intestinal flora is a pathogenic factor for chronic atrophic gastritis (CAG). Hua-Zhuo-Jie-Du (HZJD) has been shown to be an effective Chinese herbal preparation for treating CAG. However, the effects of HZJD on the intestinal flora of CAG is unclear. In this study, we probed the regulating effects of HZJD on intestinal microbes in CAG rats using 16S rRNA gene sequencing. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of HZJD preparations. We then administered 1-methyl-3-nitro-1-nitrosoguanidine (200 µg/ml) to Sprague-Dawley rats to establish a CAG model. HZJD and vitacoenzyme were administered orally to these rats over a 10 week period. Hematoxylin and eosin (H&E) staining was performed to observe the histopathology of CAG rats. A rarefaction curve, species accumulation curve, Chao1 index, and ACE index were calculated to assess the alpha diversity. Principal component analysis (PCA), non-metric multi-dimensional scaling (NMDS), and unweighted pair group method with arithmetic mean (UPGMA) were conducted to examine the beta diversity. The LEfSe method was used to identify differential bacteria. Differential function analysis used PCA based on KEGG function prediction. RESULTS: HPLC showed that our HZJD preparation method was feasible. H&E staining showed that HZJD significantly improved the pathological state of the gastric mucosa in CAG rats. The rarefaction curve and species accumulation curve showed that the sequencing data were reasonable. The Chao1 and ACE indices were significantly increased in CAG rats compared to the N group. Following HZJD and vitacoenzyme treatment, the Chao1 and ACE indices were decreased. PCA, NMDS, and UPGMA results showed that the M group was separated from the N, HZJD, and V groups, and LEfSe results showed that the relative abundance of Akkermansia, Oscillospira, Prevotella, and CF231 were significantly higher in the N group. Proteobacteria and Escherichia were significantly enriched in the M group, Allobaculum, Bacteroides, Jeotgalicoccus, Corynebacterium, and Sporosarcina were significantly enriched in the V group, and Firmicutes, Lactobacillus, and Turicibacter were significantly enriched in the HZJD group. CONCLUSION: HZJD exhibited a therapeutic effect on the intestinal flora of CAG rats.
Assuntos
Gastrite Atrófica , Microbioma Gastrointestinal , Animais , Mucosa Gástrica , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-DawleyRESUMO
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
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Medicamentos de Ervas Chinesas , Lesões Pré-Cancerosas , Neoplasias Gástricas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Mucosa Gástrica , Humanos , Medicina Tradicional Chinesa , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Huazhuojiedu decoction, a Chinese herbal preparation, has been proven to be clinically effective in treating precancerous lesions in gastric cancer (PLGC). This formula is optimized from a classic formula called "Ganluxiaodu Dan." Although some experiments have shown that Huazhuojiedu decoction is effective against PLGC, the mechanism remains unclear. AIM OF THE STUDY: To investigate the treatment of PLGC with Huazhuojiedu decoction from the perspective of lncRNA in vitro and in vivo. MATERIALS AND METHODS: A PLGC rat model was prepared and randomly divided into a Huazhuojiedu decoction group (HG), a vitacoenzyme group (VG), a model group (MG), and a normal group (CG). Each group was given a corresponding concentration of medicine and distilled water for 10 weeks. The pathological changes in the gastric mucosa were observed by hematoxylin-eosin staining (HE). High-throughput sequencing was performed to detect the differentially expressed lncRNAs in the HG, MG, and CG. Quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify differentially expressed lncRNAs, and rat-human homology information was obtained from the University of California, Santa Cruz (UCSC) Genome Database. Human gastric mucosal epithelial cells (GES-1) were used to prepare precancerous lesions of gastric cancer cells (MC). A Huazhuojiedu decoction drug-containing serum was prepared to treat the MC cells. The effects of the Huazhuojiedu decoction and the lncRNA ENST00000517368 (lnc 517368) knockdown or overexpression on PLGC cell proliferation and apoptosis were evaluated in vitro using CCK-8, flow cytometry, and RT-qPCR. RESULTS: The HE results showed that gastric mucosal pathology was significantly improved in the HG. High-throughput sequencing results showed that compared with the CG, 91 lncRNAs upregulated in the MG were restored and downregulated in the HG (P < 0.05), and 115 lncRNAs downregulated in the MG were restored and upregulated in the HG (P < 0.05). The results of RT-qPCR were consistent with the sequencing results. The differentially expressed genomic rat lncRNA ENSRNOT00000079699 is homologous to human lnc 517368. In cell experiments, high expression of lnc 517368 promoted proliferation and reduced apoptosis in PLGC cells, while the Huazhuojiedu decoction reduced the expression of lnc 517368 and improved cell morphology. CONCLUSIONS: Huazhuojiedu decoction inhibited cell proliferation and promoted apoptosis in PLGC cells, and its effect may be partially dependent on the downregulation of lnc 517368.
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Medicamentos de Ervas Chinesas/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Lesões Pré-Cancerosas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Mucosa Gástrica/patologia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Lesões Pré-Cancerosas/genética , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-Dawley , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: Hua-Zhuo-Jie-Du (HZJD), a Chinese herbal prescription consisting of 11 herbs, is commonly used in China to treat chronic atrophic gastritis (CAG). We aimed to determine the effect of HZJD on the microbiome-associated metabolic changes in CAG rats. METHODS: The CAG rat models were induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with irregular fasting and 2% sodium salicylate, which was intragastrically administrated in fasted animals for 24 weeks. The CAG rats in the Chinese medicine (CM) group were administered a daily dose of 14.81 g/kg/day HZJD, and the vitacoenzyme (V) group were administered a daily dose of 0.08 g/kg/day vitacoenzyme. All animals were treated for 10 consecutive weeks, consecutively. Hematoxylin and eosin (H&E) staining was used to assess the histopathological changes in the gastric tissues. An integrated approach based on liquid chromatograph mass spectrometer (LC-MS) metabolic profiling combined with 16S rRNA gene sequencing was carried out to assess the effects of HZJD on CAG rats. Spearman analysis was used to calculate the correlation coefficient between the different intestinal microbiota and the metabolites. RESULTS: The H&E results indicated that HZJD could improve the pathological condition of CAG rats. The LC-MS results indicated that HZJD could significantly improve 21 gastric mucosal tissue perturbed metabolites in CAG rats; the affected metabolites were found to be involved in multiple metabolic pathways, such as the central carbon metabolism in cancer. The results of 16S rRNA gene sequencing indicated that HZJD could regulate the diversity, microbial composition, and abundance of the intestinal microbiota of CAG rats. Following HZJD treatment, the relative abundance of Turicibacter was increased, and the relative abundance of Desulfococcus and Escherichia were decreased in the CM group when compared with the M group. Spearman analysis revealed that perturbed intestinal microbes had a strong correlation with differential metabolites, Escherichia exhibited a negative correlation with l-Leucine, Turicibacter was negatively correlated with urea, and Desulfococcus exhibited a positive correlation with trimethylamine, and a negative correlation with choline. CONCLUSIONS: HZJD could protect CAG by regulating intestinal microbiota and its metabolites.
RESUMO
The ability to follow spoken instructions is critical for children's learning in school and relies on the storage and processing of information in working memory. This study compared the effects of two encoding strategies (motor imagery and verbal rehearsal) on children's ability to follow spoken instructions in a working memory paradigm. A total of 146 children aged 7-12 years completed an instruction span task. In this task, children listened to a series of action-object commands and encoded them by either motor imagery or verbal rehearsal. They then attempted to recall the sequence in serial order by either enacted recall or verbal recall. Overall, children's ability to follow spoken instructions increased with age. In all age groups, children showed superior recall of instructions when they imagined the actions compared with verbal rehearsal of the actions during encoding, and this benefit of motor imagery was similar for verbal recall and enacted recall. Younger children reported motor imagery as more helpful than verbal rehearsal for remembering instructions, whereas older children considered verbal rehearsal as more useful. The study provides novel evidence for motor imagery as a superior strategy (relative to verbal rehearsal) for remembering spoken instructions in school-age children.
Assuntos
Memória de Curto Prazo , Rememoração Mental , Adolescente , Percepção Auditiva , Criança , Humanos , Aprendizagem , Instituições AcadêmicasRESUMO
BACKGROUND: The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic ß-cells, however, the physiological functions of YY1 in ß-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism. METHODS: We established two models of ß-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, ß-cell mass and ß-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of ß-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in ß-cells. RESULTS: Our results showed that loss of YY1 resulted in reduction of insulin production, ß-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic ß-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models. CONCLUSION: Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in ß-cells.