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Introduction: This study focuses on understanding the unique causes and mechanisms of "Chinese-style lurking" on WeChat among university students, within a cultural context that emphasizes collectivism and face concern. The research also looks into the moderating role of trait mindfulness. Methods: For the confirmation of these phenomena and to validate the theories, a structural equation model was constructed using the Stress-Strain-Outcome (SSO) theory and mindfulness buffering theory. The model was then tested and validated with data from 1,453 valid online surveys. These data were analyzed using the SmartPLS 4.0 software. Results: The results indicate that collectivism increases face concern, which in turn escalates online social anxiety. Face concern completely mediates between collectivism and online social anxiety, creating a serial mediation effect between face concern, online social anxiety, and lurking behavior. Additionally, trait mindfulness was found to negatively modulate the pathways from collectivism to face concern and from online social anxiety to lurking. Discussion: The findings underscore the influence of traditional Chinese culture on contemporary students' online behavior and provide a new perspective for understanding social media lurking in an Eastern context. The results suggest that a mindfulness-based approach could be used to mitigate the associated silence and anxiety.
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In this study, extrusion method was employed to fabricate alginate-zein core-shell microcapsules loaded with buckwheat honey by dropping alginate and buckwheat honey mixture solution into a 70.0 % zein ethanol solution(v/v) containing 5.0 % CaCl2 solution (wt%). The microcapsules were constructed by two parts: 1) the formation of hydrophilic beads through the crosslinking of alginate chains with Ca2+; 2) the introduction of alginate beads into the aqueous zein ethanol solution which decreased the ethanol concentration, prompting the precipitation of zein and the deposition of zein nanoparticles onto the surfaces of alginate beads. Comparing with the alginate beads, the prepared microcapsules not only possessed better water-holding capacity, but also achieved controlled release of buckwheat honey. Importantly, the microcapsules significantly retained the antioxidant activity of the buckwheat honey. Therefore, this innovative method for fabricating alginate-zein core-shell microcapsules can suggest a promising approach to broaden the application of buckwheat honey in the food field.
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Fagopyrum , Miel , Zeína , Cápsulas , Alginatos , Preparaciones de Acción Retardada , Agua , EtanolRESUMEN
In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation, the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter, Dubosiella, and Staphylococcus, and increased the abundance of Bacteroides, Blautia, and Lactobacillus. Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism, carbohydrate digestion and absorption, fatty acid biosynthesis, fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Panax , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Panax/metabolismo , Hígado/metabolismo , Ácidos Grasos Volátiles/metabolismo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
To investigate the effects of glycerol tributyrin (TB) (Triacylglycerol tributanoate) on the regulation of liver lipid metabolism by intestinal flora of grass carp (Ctenopharyngodon idellus). The compound feed with soybean oil 2.8% + fish oil 1.8%, soybean oil 6.3% + fish oil 1.8%, and soybean oil 6.2% + fish oil 1.8% + TB 0.1% was added to the basal diet as a fat source and fed to the basal (control) group, high lipid (HL) group, and tributyrin (TB) group for 12 weeks. We tested the growth performance, fat content, diversity, and abundance of gut flora and other related indexes of grass carp by Soxhlet extraction, liver tissue enzyme activity, oil red O staining, and 16S rRNA high-throughput sequencing. The results showed that the liver fat number and liver fat content of grass carp in the TB group were lower than those in the HL group, while the fattening degree was significantly higher than those in the other two groups; according to the indices such as Shannon, Ace, and Coverage, it was found that the grass carp in the TB group had the highest abundance and diversity of intestinal microflora; at the portal level, Proteobacteria and Fusobacteria were the main dominant flora in the TB group, with the number of unique OUTs accounting for about 59. 9% of the total number measured; at the genus level, the relative abundance of lipase-producing, short-chain fatty acid-associated bacteria, such as Bacillus-Lactobacillus and Bifidobacterium, was significantly lower (p < 0.05). Thus, we conclude that the addition of TB to high-fat diets can alter the structure of the intestinal microbial community and promote hepatic lipid metabolism in grass carp. TB can alleviate fatty liver in grass carp by increasing the relative abundance of short-chain fatty acids in the intestine. Meanwhile, TB inhibits the conversion of primary bile acids to secondary bile acids in the host, which can block intestinal FXR signaling and the hepatic FXR-SHP pathway, thus slowing down fat synthesis and alleviating the accumulation of liver lipids in grass carp.
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Carpas , Microbioma Gastrointestinal , Animales , Glicerol/farmacología , Glicerol/metabolismo , Metabolismo de los Lípidos , Carpas/metabolismo , Aceite de Soja , ARN Ribosómico 16S , Dieta/veterinaria , Dieta Alta en Grasa , Hígado/metabolismo , Triglicéridos/metabolismo , Aceites de Pescado/farmacología , Ácidos y Sales Biliares/metabolismo , Alimentación Animal/análisisRESUMEN
BACKGROUND: As an anticancer Chinese herbal medicine, the effective components and mechanism of Actinidia chinensis Planch (ACP, Tengligen) in the treatment of colon cancer are still unclear. In the present study, the integration of network pharmacology, molecular docking, and cell experiments was employed to study the effective mechanism of ACP against colon cancer. METHODS: The Venn diagram and STRING database were used to construct the protein-protein interaction network (PPI) of ACP-colon cancer, and further topological analysis was used to obtain the key target genes of ACP in colon cancer. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to visualize the related functions and pathways. Molecular docking between key targets and compounds was determined using software such as AutoDockTools. Finally, the effect of ACP on CT26 cells was observed in vitro. RESULTS: The study identified 40 ACP-colon key targets, including CASP3, CDK2, GSK3B, and PIK3R1. GO and KEGG enrichment analyses found that these genes were involved in 211 biological processes and 92 pathways, among which pathways in cancer, PI3K-Akt, p53, and cell cycle might be the main pathways of ACP against colon cancer. Molecular docking verified that the key components of ACP could stably bind to the corresponding targets. The experimental results showed that ACP could inhibit proliferation, induce apoptosis, and downregulate the phosphorylation of PIK3R1, Akt, and GSK3B in CT26 cells. CONCLUSION: ACP is an anti-colon cancer herb with multiple components, and involvement of multiple target genes and signaling pathways. ACP can significantly inhibit proliferation and induce apoptosis of colon cancer cells, which may be closely related to the regulation of PI3K/AKT/GSK3B signal transduction.
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Actinidia , Neoplasias del Colon , Simulación del Acoplamiento Molecular , Actinidia/genética , Farmacología en Red , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Factores de TranscripciónRESUMEN
Slow fermentable dietary fibers can be utilized by human gut microbiota in the distal region of the colon and thus exert a sufficient short-chain fatty acids (SCFAs) supplement in the distal region of the human colon. Alginate (Alg) based microgels are widely fabricated and used to control their digestion by digestive enzymes releasing active substances site-specifically. Herein, sodium alginate microgels with gradient calcium-ion (Ca2+) cross-linking densities were developed, restricting their degradation by gut microbiota. Alg microgels were prepared using high-speed shearing after Alg was cross-linked with 10, 40, and 60 mmol/L Ca2+, respectively (named 10-Alg, 40-Alg, and 60-Alg). The fluorescence and atomic force microscopic results showed that the 40-Alg particle has the densest structure among the three cross-linked Alg. In vitro human fecal fermentation results revealed that the Ca2+ cross-linking exerted more restricting effects than delaying effects on the fermentation of Alg, and the 40-Alg exhibited the slowest fermentation rate and the least fermentation extent, by characterizing the residual total carbohydrate content, residual monosaccharide content, pH, and total short-chain fatty acids. The 16S rRNA gene sequencing results indicated that cross-linking structures shaped a high specifical Bacteroides-type microbial community and that OTU205 (Bacteroides_xylanisolvens) highly correlated to the cross-linking density (R = 0.65, p = 0.047). In sum, Ca2+ cross-linking generated a dense and compact structure of sodium alginate that facilitated a more restricted fermentation property and specificity-targeting microbial community structure in comparison to the original sodium alginate.
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Alginatos , Microgeles , Humanos , Fermentación , Alginatos/química , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Ácidos Grasos Volátiles/metabolismoRESUMEN
Salidroside (Sal) possesses several pharmacological activities, such as antiaging, and anti-inflammatory, antioxidant, anticancer activities, and proliferation-promoting activities, but the effects of Sal on oocytes have rarely been reported. In the present study, we evaluated the beneficial effects of Sal, which is mainly found in the roots of Rhodiola. Porcine cumulus oocyte complexes were cultured in IVM medium supplemented (with 250 µmol/L) with Sal or not supplemented with Sal. The maturation rate in the Sal group increased from 88.34 ± 4.32% to 94.12 ± 2.29%, and the blastocyst rate in the Sal group increased from 30.35 ± 3.20% to 52.14 ± 7.32% compared with that in the control group. The experimental groups showed significant improvements in the cumulus expansion area. Sal reduced oocyte levels of reactive oxygen species (ROS) and enhanced intracellular GSH levels. Sal supplementation enhanced the mitochondrial membrane potential (MMP), ATP level, and mtDNA copy number, which shows that Sal enhances the cytoplasmic maturation of oocytes. Oocytes in the Sal group exhibited slowed apoptosis and reduced DNA breakage. Cell cycle signals and oocyte meiosis play important roles in oocyte maturation. The mRNA expressions of the MAPK pathway and MAPK phosphorylation increased significantly in the Sal group. The mRNA expression of the oocyte meiosis gene also increased significantly. These results show that Sal enhances the nuclear maturation of oocytes. Moreover, Sal increased the number of blastocyst cells, the proliferation of blastocysts, and the expressions of pluripotency genes. Sal down-regulated apoptosis-related genes and the apoptotic cell rate of blastocysts. In summary, our results demonstrate that Sal is helpful to improving the quality of porcine oocytes in vitro, and their subsequent embryonic development.
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Suplementos Dietéticos , Meiosis , Femenino , Embarazo , Animales , Porcinos , Desarrollo Embrionario , ARN MensajeroRESUMEN
BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.
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Glucemia , Ayuno , Metales , Selenio , Anciano , Femenino , Humanos , Teorema de Bayes , Glucemia/análisis , Cobalto/orina , Pueblos del Este de Asia , Ayuno/sangre , Ayuno/orina , Vida Independiente , Selenio/orina , Vanadio/orina , Espectrometría de Masas , Calcio/orina , Magnesio/orina , Molibdeno/orina , Metales/orina , Mezclas Complejas/orinaRESUMEN
Background: Solanum nigrum L. (SNL) (Longkui) is a Chinese herb that can be used to treat colon cancer. The present study explored the components and mechanisms of SNL in treating colon cancer by using network pharmacology and molecular docking. Methods: The components of SNL were collected from the TCMSP, ETCM, HERB, and NPASS databases. Meanwhile, the target proteins of these ingredients were collected/predicted by the TCMSP, SEA, SwissTargetPrediction, and the STITCH databases colon cancer-related target genes were identified from TCGA and GTEx databases. The interaction networks were established via Cytoscape 3.7.2. Gene Ontology and KEGG pathways were enriched by using the David 6.8 online tool. Finally, the binding of key components and targets was verified by molecular docking, and the cellular thermal shift assay (CETSA) was used to detect the efficiency of apigenin and kaempferol binding to the AURKB protein in CT26 cells. Results: A total of 37 SNL components, 796 SNL targets, 5,356 colon cancer genes, and 241 shared targets of SNL and colon cancer were identified. A total of 43 key targets were obtained through topology analysis. These key targets are involved in multiple biological processes, such as signal transduction and response to drug and protein phosphorylation. At the same time, 104 signaling pathways, such as pathways in cancer, human cytomegalovirus infection, and PI3K-Akt signaling pathway, are also involved. The binding of the four key components (i.e., quercetin, apigenin, kaempferol, and luteolin) and the key targets was verified by molecular docking. The CETSA results showed that apigenin and kaempferol were able to bind to the AURKB protein to exert anti-CRC effects. Conclusions: Quercetin, apigenin, kaempferol, and luteolin are the main components of SNL in treating colon cancer. SNL regulates multiple bioprocesses via signaling pathways, such as pathways in cancer, PI3K-Akt, and cell cycle signaling pathways.
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Recently, endorhizospheric microbiota is realized to be able to promote the secondary metabolism in medicinal plants, but the detailed metabolic regulation metabolisms and whether the promotion is influenced by environmental factors are unclear yet. Here, the major flavonoids and endophytic bacterial communities in various Glycyrrhiza uralensis Fisch. roots collected from seven distinct places in northwest China, as well as the edaphic conditions, were characterized and analyzed. It was found that the soil moisture and temperature might modulate the secondary metabolism in G. uralensis roots partially through some endophytes. One rationally isolated endophyte Rhizobium rhizolycopersici GUH21 was proved to promote the accumulation of isoliquiritin and glycyrrhizic acid significantly in roots of the potted G. uralensis under the relatively high-level watering and low temperature. Furthermore, we did the comparative transcriptome analysis of G. uralensis seedling roots in different treatments to investigate the detailed mechanisms of the environment-endophyte-plant interactions and found that the low temperature went hand in hand with the high-level watering to activate the aglycone biosynthesis in G. uralensis, while GUH21 and the high-level watering cooperatively promoted the in planta glucosyl unit production. Our study is of significance for the development of methods to rationally promote the medicinal plant quality. KEY POINTS: ⢠Soil temperature and moisture related to isoliquiritin contents in Glycyrrhiza uralensis Fisch. ⢠Soil temperature and moisture related to the hosts' endophytic bacterial community structures. ⢠The causal relation among abiotic factors-endophytes-host was proved through the pot experiment.
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Flavonas , Glycyrrhiza uralensis , Plantas Medicinales , Glycyrrhiza uralensis/química , Glycyrrhiza uralensis/metabolismo , Glycyrrhiza uralensis/microbiología , Endófitos , Terpenos/metabolismo , Glicósidos/metabolismo , Raíces de Plantas/microbiologíaRESUMEN
Oleogels containing less saturated and trans-fats were considered as an ideal option to replace the solid fats in foods. In this research, oleogel was fabricated by dispersing soy fiber particles (SFP) in soy oil, and further it was used in bread preparation. Effect of the particle size, particle content and the second fluid content on the formation of oleogels were evaluated, based on the appearance and rheological properties. Results showed that the suspension of SFP in soy oil (24%, w/w) could be transformed into gel-like state, upon the addition of the second fluid. The SFP based networks were dominated by the capillary force which was originated from the second fluid. The rheological properties and yield stress of the oleogels could be modulated by particle size and particle content of SFP in oil phase, as well as the second fluid content in the system. When the oleogels were applicated in bread preparation, a layered structure could be formed in the bread, indicating the possibility of replacing the solid fats in bakery products by our oleogels. Our results offered a feasibility approach for oil structuring with natural raw materials, and developed a new approach to replace the solid fats in foods.
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Compuestos Orgánicos , Aceite de Soja , Compuestos Orgánicos/química , Aceite de Soja/química , Pan , Fenómenos QuímicosRESUMEN
Colorectal cancer (CRC) is a disease with complex pathogenesis, it is prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, and immunotherapy remain the main treatments for CRC, but improvement in the overall survival rate and quality of life is urgently needed. Traditional Chinese medicine (TCM) has a long history of preventing and treating CRC. It could affect CRC cell proliferation, apoptosis, cell cycle, migration, invasion, autophagy, epithelial-mesenchymal transition, angiogenesis, and chemoresistance by regulating multiple signaling pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/ß-catenin, epidermal growth factor receptors, p53, TGF-ß, mTOR, Hedgehog, and immunomodulatory signaling pathways. In this paper, the main signaling pathways and potential targets of TCM and its active ingredients in the treatment of CRC were systematically summarized, providing a theoretical basis for treating CRC with TCM and new ideas for further exploring the pathogenesis of CRC and developing new anti-CRC drugs.
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Prenatal maternal nutrient supplementation has been reported to be associated with offspring obesity, but the reports are inconsistent and have mainly ignored the differences between the total children population and children born small for gestational age (SGA). This study aimed to examine the joint effects of folic acid, iron, and multivitamin supplementation during pregnancy on the risk of obesity in preschoolers born SGA. A total of 8918 children aged 3-6.5 years born SGA were recruited from Longhua District in Shenzhen of China in 2021. Their mothers completed a structured questionnaire about the child's and parents' socio-demographic characteristics, maternal prepregnant obesity, and mothers' prenatal supplementation of folic acid, iron, and multivitamin. In addition, the children's current weight and height were measured by trained nurses. Logistic regression models were used to analyze the associations between prenatal supplementations and the current presence of childhood obesity. After controlling for potential confounders, the results of the logistic regression analysis showed that prenatal supplement of folic acid (OR = 0.72, 95% CI = 0.55~0.93) was associated with a lower likelihood of being an obese preschooler born SGA. In contrast, the ingestion of multivitamin or iron supplements during pregnancy did not seem to be related to the likelihood of childhood obesity in preschoolers born SGA. Moreover, cross-over analysis of prenatal folic acid and multivitamin obtained significant negative associations of prenatal folic acid supplement only (OR = 0.73, 95% CI = 0.55~0.97) and combination supplement of folic acid and multivitamin (OR = 0.67, 95% CI = 0.50~0.90) with obesity of preschoolers born SGA; while the cross-over analysis of prenatal folic acid and iron observed significant negative associations between obesity of preschoolers born SGA and a combination supplement of folic acid and iron (OR = 0.70, 95% CI = 0.52~0.96). Furthermore, the aforementioned significant associations were only found in girls and not in boys when the analyses were stratified by sex. Our findings suggest that the prenatal folic acid supplementation may decrease the risk of obesity in preschool girls born SGA, and that this effect may be modified by prenatal multivitamin or iron supplementation.
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Enfermedades del Recién Nacido , Obesidad Infantil , Embarazo , Masculino , Recién Nacido , Femenino , Niño , Humanos , Preescolar , Ácido Fólico/farmacología , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Suplementos Dietéticos , Vitaminas , HierroRESUMEN
Diabetic wound is one of the most intractable chronic wounds that is prone to bacterial infection. Hypoxia is an important feature in its microenvironment. However, it is challenging for antimicrobial therapy to directly apply the existing hypoxia-responsive drug delivery systems due to the active targeting deficiency and the biofilm obstacle. Herein, we customizes a hypoxia-responsive carrier, lactose-modified azocalix[4]arene (LacAC4A) with the ability to actively target and inhibit biofilm. By loading ciprofloxacin (Cip), the resultant supramolecular nanoformulation Cip@LacAC4A demonstrates enhanced antibacterial efficacy resulting from both the increased drug accumulation and the controlled release at the site of infection. When applied on diabetic wounds together with multidrug-resistant Pseudomonas aeruginosa infection in vivo, Cip@LacAC4A induces definitely less inflammatory infiltration than free Cip, which translates into high wound healing performance. Importantly, such design principle provides a direction for developing antimicrobial drug delivery systems.
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Antiinfecciosos , Diabetes Mellitus , Infecciones por Pseudomonas , Humanos , Pseudomonas aeruginosa , Lactosa , Pruebas de Sensibilidad Microbiana , Preparaciones de Acción Retardada , Úlcera/tratamiento farmacológico , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Biopelículas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Sistemas de Liberación de Medicamentos , Hipoxia/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
AIM OF THE REVIEW: This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), and provide support for further investigation on TCM and its active ingredients. MATERIALS AND METHODS: Literature survey was conducted using PubMed, Web of Science, Google Scholar, CNKI, and other databases, with "Alzheimer's disease," "traditional Chinese medicine," "medicinal herb," "Chinese herb," and "natural plant" as the primary keywords. RESULTS: TCM could modulate signal pathways related to AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, and PI3K/Akt/mTOR, as well as SIRT1 and PPARα pathway. It could regulate crosstalk between pathways through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating ubiquitin-proteasome system function, modulating autophagy, and eventually improving cognitive impairment in patients with AD. CONCLUSION: TCM could be multilevel, multitargeted, and multifaceted to prevent and treat AD. In-depth research on the prevention and treatment of AD with TCM could provide new ideas for exploring the pathogenesis of AD and developing new anti-AD drugs.
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Enfermedad de Alzheimer , Medicamentos Herbarios Chinos , Enfermedad de Alzheimer/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Glucógeno Sintasa Quinasa 3 , Humanos , Medicina Tradicional China , Fosfatidilinositol 3-Quinasas , Complejo de la Endopetidasa Proteasomal , Transducción de Señal , Serina-Treonina Quinasas TOR , UbiquitinasRESUMEN
Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is a pharmacologically active flavone that has been isolated from a variety of medicinal plants and possesses a number of pharmacological properties. This study evaluates the antioxidant and antiapoptotic effects of eupatilin on cisplatin-induced ototoxicity using in vitro and in vivo models including HEI-OC1 cells, cochlear hair cells, and zebrafish. Employing a CCK8 assay and Annexin V-FITC/PI double staining, we found that eupatilin significantly alleviated cisplatin-induced apoptosis and increased hair cell viability. The level of reactive oxygen species (ROS) was evaluated by CellROX green and MitoSOX Red staining. The results showed that eupatilin possesses antioxidant activity. MitoTracker Red staining indicated that eupatilin remarkably decreased mitochondrial damage. Furthermore, we demonstrated that eupatilin protects hair cells from cisplatin-induced damage. Mechanistic studies in cisplatin-induced HEI-OC1 cells revealed that eupatilin promoted Bcl-2 expression, downregulated Bax expression, reversed the increase in caspase-3 and PARP activity, and reduced the expression of phosphorylated p38 and JNK. Our data suggest a novel role for eupatilin as a protective agent against ototoxic drug-induced hair cell apoptosis by inhibiting ROS generation and modulating mitochondrial-related apoptosis.
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Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Cisplatino/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/uso terapéutico , Células Ciliadas Auditivas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Animales , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , Humanos , Ratones , Pez CebraRESUMEN
BACKGROUND: The evidence about the effect of essential trace element (ETE) mixture on cognitive function amongst older adults is limited. This study aims to evaluate the associations of single ETEs and ETE mixture with cognitive function using a representative sample of community-dwelling older adults in China. METHODS: A total of 3814 older adults were included in the study. Urinary concentrations of selenium (Se), vanadium (V), cobalt (Co), strontium (Sr), and molybdenum (Mo) were detected by inductively coupled plasma mass spectrometry. Cognitive function in older adults was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Linear regression and Bayesian kernel machine regression (BKMR) were performed to explore the associations of single ETEs and ETE mixture with cognitive function, respectively. RESULTS: Linear regression showed that urinary levels of Se and V were positively associated with MMSE scores in the adjusted single-element models. BKMR also showed marginally positive associations of Se and V with MMSE scores. Moreover, higher urinary levels of ETE mixture were significantly associated with increased MMSE scores in a dose-response pattern, and Se was the most important contributor within the mixture. Both Se and V demonstrated positive additive effects on the associations of other ETEs with MMSE scores, whereas Co had a negative additive effect. CONCLUSIONS: V and Se are positively associated with cognitive function, individually and as a mixture. ETE mixture exhibits a linear dose-response association with improved cognitive function, with Se being the most important component within the mixture. Mixture analyses rather than single ETE analyses may provide a real-world perspective on the relationship between ETE mixture and cognitive function. Further cohort studies are needed to clarify the association of multiple ETEs with cognitive function.
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Selenio , Oligoelementos , Anciano , Teorema de Bayes , Cognición , Humanos , Vida IndependienteRESUMEN
Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease with a high mortality of ~ 35%. The lack of approved treatments for MERS-CoV infection underscores the need for a user-friendly system for rapid drug screening. In this study, we constructed a MERS-CoV replicon containing the Renilla luciferase (Rluc) reporter gene and a stable luciferase replicon-carrying cell line. Using this cell line, we showed that MERS-CoV replication was inhibited by combined application of lopinavir and ritonavir, indicating that this cell line can be used to screen inhibitors of MERS-CoV replication. Importantly, the MERS-replicon cell line can be used for high-throughput screening of antiviral drugs without the need for live virus handling, providing an effective and safe tool for the discovery of antiviral drugs against MERS-CoV.
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Antivirales , Línea Celular , Evaluación Preclínica de Medicamentos , Coronavirus del Síndrome Respiratorio de Oriente Medio , Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Lopinavir/uso terapéutico , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , ReplicónRESUMEN
Magnetic hyperthermia therapy (MHT) has been considered as an excellent alternative for treatment of deep tumor tissue; however, up-regulation of heat shock proteins (HSPs) impairs its hyperthermal therapeutic effect. Reactive oxygen species (ROS) and competitive consumption of ATP are important targets that can block excessive HSP generation. We developed a magnetic nanocatalytic system comprised of glucose oxidase (GOD)-loaded hollow iron oxide nanocatalysts (HIONCs) to drive starvation-chemodynamic-hyperthermia synergistic therapy for tumor treatment. The Fe2+ present in HIONCs contributed to ROS generation via the Fenton reaction, relieving thermo-resistance and inducing cell apoptosis by chemodynamic action. The Fenton effect was enhanced through the conditions created by increased MHT-related temperature, GOD-mediated H2O2 accumulation, and elevated tumor microenvironment acidity. The HIONCs catalase-like activity facilitated conversion of H2O2 to oxygen, thereby replenishing the oxygen levels. We further demonstrated that locally injected HIONCs-GOD effectively inhibited tumor growth in PC3 tumor-bearing mice. This study presents a multifunctional nanocarrier system driving starvation-chemodynamic-magnetic-thermal synergistic therapy via ROS and oxygen modulation for prostate tumor treatment.